Archive for the ‘Research Projects’ Category
Genome Maps Solve Medical Mystery For Calif. Twins
Last Updated on Thursday, 16 June 2011 10:51 Written by admin Thursday, 16 June 2011 10:51
Ever since scientists began to sequence the entire genomes of individuals —beginning with those of Nobelist James Watson and scientific entrepreneur J. Craig Venter in 2007 — skeptics have wondered just how useful this elegant and expensive trick would become.
A pair of 14-year-old twins, Alexis and Noah Beery, now provide a compelling answer, even if it’s not yet clear how generalizable their case is to others with genetic disorders.
Whole-genome sequencing has enabled doctors to provide the Beery twins with a simple, highly effective treatment for a rare condition called DRD, or dopa-responsive dystonia. The tale of their cure appears in this week’s issue of the journal Science Translational Medicine.
The twins were diagnosed with cerebral palsy at age two. But their mother, Retta Beery, didn’t think that was correct. For one thing, Alexis’s contorted posture and jerky movements always seemed to be better in the morning and increased as the day went on.
Turns out DRD is known for these diurnal variations, as Retta found out through dogged research. That led to a diagnosis of DRD when the twins were five. Since DRD was thought to be a deficiency of the neurotransmitter dopamine, low doses of a drug called L-dopa (also used for Parkinson’s disease) rather miraculously made the twins’ “cerebral palsy” go away within days.
But other symptoms persisted and worsened. At age 14, Noah had hand tremors, awkwardness and attentional problems. More alarmingly, Alexis had breathing problems due to spasms in her larynx. But when doctors probed for an explanation of these symptoms, the twins tested negative for known mutations of two genes known to be involved in DRD.
As it happens, the twins’ father, Joe Beery, works for a California biotech company that makes DNA sequencing machines. So the parents wondered if a deep dive into their twins’ DNA might explain the nature of their particular genetic defect.
Scientists at Baylor College of Medicine, a pioneer in whole-genome sequencing of individuals, thought it was worth a go. They sequenced the genomes of the twins, their older brother, their parents and their grandparents.
Comparing the results, the researchers found that the twins both inherited a gene variant from each parent that, together, led them to have low levels of not just dopamine but two other neurotransmitters, serotonin and noradrenalin.
The twins’ neurologist, Jennifer Friedman of Rady Children’s Hospital in San Diego, suggested giving the teenagers a supplement called 5-HTP that’s a precursor for serotonin.
Together with the L-dopa, the additional supplement has improved Alexis’s breathing point to the point that she’s now running track again. Noah’s handwriting and athletic performance have improved, and he’s better able to focus in school.
And there’s an intriguing bonus. Scientists think the gene mutation that the Beery twins inherited from their mother may be responsible for a pattern of a neuromuscular disease called fibromyalgia in her family. Fibromyalgia sometimes responds to anti-depressants called SSRIs that raise serotonin levels.
If that hypothesis pans out, it would suggest that rare genetic disorders such as DRD are just the most dramatic manifestation – in people who inherit a double dose of certain gene variants – of much more common disorders such as fibromyalgia among people who have a single copy of the mutation.
Study authors say the Beerys’ case shows how genomics will ultimately revolutionize medicine by making diagnosis more precise and pointing toward life-changing treatments. Other cases are beginning to pop up, such as a Wisconsin boy whose rare disease was diagnosed by whole-genome sequencing and subsequently treated with a bone marrow transplant. (His story appeared in a Pulitzer Prize-winning series by the Milwaukee Journal-Sentinel.)
Cost is still a big obstacle. At the time the Beery family’s genomes were sequenced, it cost around $100,000 per person. Dr. Richard Gibbs of Baylor says now, less than two years later, it would cost about half as much – less than $10,000 for the actual sequencing, plus the cost of computer processing of the results and validation.
The skeptics also point out that not all genetic insights from sequencing will lead to such cheap, simple and effective treatments as the Beery twins got.
Source: http://www.npr.org/blogs/health/2011/06/16/137204964/genome-maps-solve-medical-mystery-for-calif-twins
Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, Genetics & Pharmacogenetics, Medicinal Chemistry, North America, Research Projects, USA and Canada | Comments Off
Playing God; Is Genetic Testing The Answer To A More Pure Species?
Last Updated on Monday, 13 June 2011 04:09 Written by admin Monday, 13 June 2011 04:09
Some parents don’t want to know the sex of their upcoming child. Others do. DNA profiling has been a hot topic amongst scientists for years and this week the topic heats up even more as a few reports published last December are now appearing on the scientific grid months later. Included in the studies is news that doctors could essentially reconstruct a baby’s genetic makeup by recovering fragments of fetal DNA from the mother’s bloodstream and determine medical conditions like Down syndrome, but also things like eye color and height and even the risk for developing depression or Alzheimer’s disease and other ailments, leaving less to fate than ever before.
Marcy Darnovsky of the Center for Genetics and Society in Berkeley, California explains:
“This really changes the experience of what it will be like to be pregnant and have a child. I keep coming up with the word, game-changer.”
Jaime King, an associate professor at the University at California Hastings College of Law in San Francisco made the following comments:
“That’s a very big burden to place on would-be parents. At the moment these things happen, it’s just you there by yourself. Some people might like that level of control, but others would be happier to leave things up to chance a little more.”
The DNA of a fetus has long been recoverable through medical procedures, with a small risk of miscarriage. But a blood test would be free of that risk, which should make many more women interested in it and doctors willing to test for a wider range of conditions, some experts say. And the results could come early enough to allow for an abortion before the pregnancy is even obvious. There lies the controversy and a barrage of moral and political fire.
Dr. Brian Skotko, a board member of the National Down Syndrome Society comments:
“If no limitations are put on, you can have a couple get a prenatal genetic test in the future saying their fetus has … a 60% chance of having breast cancer at the age of 60 and a 30% chance of being gay. The ultimate question for society is what forms of human variation are valuable?”
Should a woman be allowed to get an abortion for any reason, even a trivial one like test results about height or eye color? Some state governments have passed laws outlawing abortions on the basis of sex, she said. But it’s not clear whether those are constitutional, and a woman might simply not reveal her true reasons for wanting the abortion, King said.
Skotko points out that people use their own personal perspective in deciding what they want for their children. Some couples who are deaf from a genetic condition already use current technology to avoid having children with normal hearing.
“It’s their lens by which they view the world, and they want a child who views the world through that same lens.”
A human embryo contains 46 chromosomes organized into 23 pairs: 22 pairs of non-sex chromosomes, called autosomes, and one pair of sex chromosomes (XX in a female and XY in a male). One chromosome in each pair is inherited from the mother and one from the father.
Located along these chromosomes are approximately 25,000 genes that carry instructions for making proteins. Through the proteins they encode, your genes determine how your body develops and functions.
Source:http://www.medicalnewstoday.com/articles/228350.php
Posted under DNA Reasearch, Genetics & Pharmacogenetics, North America, Research Projects, USA and Canada | Comments Off
Large Amounts of Coffee Cause Hallucinations, Study Finds
Last Updated on Wednesday, 8 June 2011 11:20 Written by admin Wednesday, 8 June 2011 11:20
Big coffee drinkers are taking a latte break from reality, with half of them likely to hallucinate or hear things, the Herald Sun reported Wednesday.
If the break is supposed to be a stress-buster — as it often is — that makes things worse. And if a cigarette is involved, you’re playing with fire.
Research at Victorian university La Trobe found that stressed coffee lovers are three times more likely to see or hear imaginary things than everyone else.
In tests, they heard Bing Crosby singing “White Christmas” — or at least thought they did.
Professor Simon Crowe tested 92 people with varied caffeine-intake and stress levels. Subjects thought they were doing hearing tests and were initially subjected to Bing.
Then they were played three minutes of static hiss and asked to press a buzzer if they heard snippets of White Christmas in there — which there weren’t.
On average, low-caffeine subjects heard it once. But stressed coffee guzzlers buzzed three times.
“If you are stressed and have a high level of caffeine, you are more likely to notice things that aren’t there, see things that aren’t there,” Crowe said.
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Bristol, Roche team up on melanoma study
Last Updated on Thursday, 2 June 2011 03:46 Written by admin Thursday, 2 June 2011 03:46
(Reuters) – Bristol-Myers Squibb and Roche Holding AG said on Thursday they would evaluate their respective cancer drugs as a potential combination therapy for metastatic melanoma.
The collaboration involves a Phase I/II study with Bristol’s recently approved Yervoy and Roche’s experimental drug, vemurafenib, to determine the safety and efficacy of the combination in treating the deadliest form of skin cancer.
The announcement comes as the American Society of Clinical Oncology meeting begins this weekend in Chicago, where emerging treatments for melanoma will be in the spotlight.
Among the most eagerly anticipated studies being presented at the ASCO meeting will be a Phase III trial intended to show that vemurafenib extended the lives of patients with advanced melanoma, and another study comparing Yervoy to chemotherapy in patients with the fatal disease.
Yervoy won U.S. approval in March for patients with inoperable or metastatic melanoma, making it the first new treatment option in many years for patients for whom there was little hope and virtually no effective medicines.
Roche and Japanese drugmaker Daiichi Sankyo Co recently submitted U.S. and European applications seeking approval for vemurafenib. The drug was developed by Roche’s Genentech unit and Plexxikon, which was recently acquired by Daiichi.
Vemurafenib, a so-called BRAF inhibitor, is designed to selectively target and inhibit a mutated form of the BRAF protein found in about half of all cases of melanoma. The combination study with Yervoy will be in patients with BRAF-mutated metastatic melanoma, Roche said.
Roche is also developing a combination diagnostic to help identify those patients with the BRAF mutation who are likely to benefit from vemurafenib.
“We are entering a new era for melanoma, and are committed to studying exciting combinations with investigational medicines in our own pipeline,” Roche Chief Medical Officer Hal Barron said in a statement.
If proven effective and approved the Yervoy-vemurafenib combination would be an extremely expensive treatment option that could meet with reimbursement resistance from government programs and health insurers.
Bristol priced a four-infusion course of Yervoy at about $120,000. Vemurafenib will likely also command premium pricing if it too demonstrates an ability to help patients live longer.
More than 70,000 people in the United States and 160,000 worldwide are diagnosed with melanoma each year, according to the American Cancer Society. The five-year survival rate for the aggressive cancer is just 15 percent.
Source: http://www.reuters.com/article/2011/06/02/us-bristol-roche-melanoma-idUSTRE75151W20110602
Posted under Cancer Research, Oncology Research, Research Projects | Comments Off
Smelly chemicals confuse mosquitoes
Last Updated on Wednesday, 1 June 2011 03:03 Written by admin Wednesday, 1 June 2011 03:03
Chemicals which interfere with a mosquito’s ability to sniff out humans have been developed by US researchers, according to research in Nature.
It is hoped they could be used to develop the next generation of mosquito traps and repellents.
A UK expert said the discovery could be a “major step forward” if the chemicals were safe and cheap.
Female mosquitoes use carbon dioxide in people’s exhaled breath to find their next meal.
They can detect minute changes in the concentration of the gas and track it back to a human breath.
This knowledge is already used in carbon dioxide traps, but requires dry ice or gas cylinders – which mean they are rarely used in developing countries.
Researchers have been looking for chemicals which can disrupt or confuse a mosquito’s carbon dioxide sense.
Deception
Scientists at the University of California, Riverside, tested smelly chemicals on three species of mosquito: Anopheles gambiae, which spreads malaria; Culex quinquefasciatus, which spreads filariasis and West Nile virus; and Aedes aegypti which spreads dengue and yellow fever.
Between them these insects are thought to spread disease to half a billion people each year and cause millions of deaths.
The researchers identified three groups of chemicals, which disrupt a mosquito’s carbon dioxide receptors.
One mimicked carbon dioxide and could be used as bait in insect traps, another prevented the mosquito from detecting carbon dioxide and the last group tricked the mosquito’s brain into thinking it was surrounded by huge quantities of the gas – so it could not pick which way to go.
Professor Anandasankar Ray, from the University of California, Riverside, said: “These chemicals offer powerful advantages as potential tools for reducing mosquito-human contact, and can lead to the development of new generations of insect repellents and lures.
“The identification of such odour molecules, which can work even at low concentrations, and are therefore economical, could be enormously effective in compromising the ability of mosquitoes to seek humans, thus helping control the spread of mosquito-borne diseases.”
Carbon dioxide is not the only way mosquitoes can find their dinner however, as the smell of human sweat and skin can also be used.
Dr James Logan, from the London School of Hygiene and Tropical Medicine, said: “Whilst this is an exciting study, the authors are yet to show that the chemicals are capable of protecting a human being from being bitten.
“Although carbon dioxide is an important cue for mosquitoes, we know that mosquitoes respond differently to a trap releasing carbon dioxide than to a real human being, which releases a complex mixture of many attractive chemicals, heat, visual cues and moisture.
“The key question is – do the ‘response modifying odours’ actually protect a human being?”
The chemicals also need to be used at high concentrations, which could be hazardous to human health. The researchers say their next step is to develop safer chemicals.
Dr Nikolai Windbichler, from Imperial College London, said work needed to be done to ensure they were safe and could be produced at low cost.
He added: “These compounds have novel and desirable properties because they can confuse the mosquitoes’ host seeking behaviour even when the substances are no longer present or the mosquitoes have left the area of application.
“This, if realised, could be a major step forward and could protect large groups of people or large areas, something that is not currently feasible with existing repellents.”
Mark Stopfer, from the US National Institutes of Health, said the study offered “a promising line of defence.”
Source: http://www.bbc.co.uk/news/health-13614781
Posted under Discoveries, Innovations and Patents, Reports, Research Projects | Comments Off
Researchers Find Cousin of Hepatitis C Virus in Dogs
Last Updated on Tuesday, 24 May 2011 02:45 Written by admin Tuesday, 24 May 2011 02:45
MONDAY, May 23 (HealthDay News) — Researchers report that they’ve discovered a virus similar to the human hepatitis C virus in dogs, a finding that might provide insight into how the germ evolved in people and perhaps lead to better treatments.
About 200 million people around the world are thought to suffer from hepatitis C, including an estimated 3.2 million chronically infected people in the United States. Many don’t know they’re infected with the liver-damaging virus that causes the disease, which means they can spread it to others without realizing it.
The new findings suggest that hepatitis C may have “jumped” from dogs to humans more than five centuries ago, the researchers said.
“Considering the origin of HIV, we expected to find the closest homologs, or genetic relatives, of [hepatitis C virus] in non-human primates,” study author Dr. Amit Kapoor, an investigator with Columbia University’s Mailman School of Public Health’s Center for Infection and Immunity, said in a news release.
“However,” Kapoor added, “while we were analyzing samples from dogs involved in outbreaks of respiratory disease, we came upon a virus that was more similar to HCV than other viruses of the same family. So far, we have only detected [the virus] in sick animals, a few of which had died of unknown causes. Because of its close genetic similarity to HCV, we suggested the name of canine hepacivirus.”
Study co-author Dr. Charles Rice, scientific and executive director of the Center for the Study of Hepatitis C at The Rockefeller University, said in the news release that the beginnings of hepatitis C “remain a mystery. These findings underscore the need to look beyond primates for clues to the origins.”
Scientists say there’s no risk of modern-day dogs infecting people with either human hepatitis C or the canine form.
Hepatitis C is a liver disease that’s typically spread through contact with infected blood. It can also spread through sex with an infected person and from mother to baby during childbirth, according to the U.S. National Institutes of Health.
The study appears in this week’s issue of the Proceedings of the National Academy of Sciences.
Source: http://health.usnews.com/health-news/family-health/digestive-disorders/articles/2011/05/23/researchers-find-cousin-of-hepatitis-c-virus-in-dogs
Posted under Discoveries, Innovations and Patents, Medicinal Chemistry, North America, Research Projects, USA and Canada, Veterinary Research | Comments Off
Bacterium that nips malaria in the bud ‘identified’
Last Updated on Friday, 13 May 2011 10:48 Written by admin Friday, 13 May 2011 10:48
Scientists claim to have identified a bacterium which nips malaria in the bud by stopping the development of Plasmodium falciparum parasite that causes the disease in humans.
Malaria afflicts more than 225 million people worldwide. Each year, the disease kills nearly 800,000 people.
Now, a team at the Johns Hopkins Bloomberg School of Public Health has found that the Enterobacter bacterium is part of the naturally occurring microbial flora of the mosquito’s gut and kills the parasite by producing reactive oxygen species, the ‘Science’ journal reported.
“In this study we show that certain bacteria can directly block the malaria parasite’s development through the production of free radicals that are detrimental to Plasmodium in the mosquito gut.
“We are particularly excited about this discovery because it may explain why mosquitoes of the same species and strain sometimes differ in their resistance to the parasite, and we may also use this knowledge to develop novel methods to stop the spread of malaria.
One biocontrol strategy may, for example, rely on the exposure of mosquitoes in the field to this natural bacterium, resulting in resistance to the malaria parasite,” said George Dimopoulos, who led the team.
In their study, the scientists isolated the Enterobacter bacterium from the midgut of Anopheles mosquitoes collected near their institute located in southern Zambia.
About 25 percent of the mosquitoes collected contained the specific bacteria strain. Laboratory studies showed the bacterium inhibited the growth of Plasmodium up to 99 per cent, both in the mosquito gut and in a test tube culture of the human malaria parasite. Higher doses of bacteria had a greater impact on Plasmodium growth.
Source: http://www.indianexpress.com/news/bacterium-that-nips-malaria-in-the-bud-identified/789966/
Posted under Cell Analysis, Discoveries, Innovations and Patents, Reports, Research Projects | Comments Off
Iona Chemistry Professor Researches Cure For ALZ
Last Updated on Monday, 20 December 2010 03:17 Written by Editor Monday, 20 December 2010 03:17
New Rochelle, NY – Do curry spice, wine and apple skins hold the answer for finding a cure for Alzheimer’s disease, Parkinson’s disease and other neurological disorders?
The results of a laboratory research project, recently published in the Journal of Neurochemistry, show that a chemical compound derived from these natural products may be used in neutralizing the toxic effects of chemicals associated with some debilitating and life-threatening neurological diseases.
The findings are the result of a four-year study undertaken by Terrence Gavin, Ph.D., a chemistry professor at Iona College and Richard M. LoPachin, Ph.D, a neurochemist and director of research in the Department of Anesthesiology at Montefiore Medical Center and the Albert Einstein College of Medicine.
In lab experiments it was found that the compound, called 2-ACP, completely protects nerve cells from the harmful effects of type-2 alkenes. There is growing evidence that exposure to type 2-alkenes, which are found in the smoke inhaled from cigarettes, the exhaust of automobiles and even in French fried potatoes, can increase the chances of developing Alzheimer’s and otherneurological conditions. In addition, studies
have shown type-2 alkenes are being produced within the nerve endings during the disease process that presumably initiates Alzheimer’s.
Dr. Gavin said: “The research Dr. LoPachin and I undertook is promising because chemical compounds extracted from curry spice, red wine and apple skins, which are widely used natural products, have already been clinically demonstrated to have neuroprotective properties. This suggests it would be safe and effective to treat humans with the 2-ACP compound.”
He added: “But, these molecular findings worked in laboratory cultures. We now need to confirm the effects of 2-ACP in animal studies. That will be the focus of our efforts in the coming months.”
In addition, Dr. Gavin and some of his students
at Iona will be looking for new compounds that will be as good or better than 2-ACP in combating the effects of type 2-alkenes. “Our goal is to have new compounds ready for testing in six months. This is a very exciting scientific exploration,” Dr. Gavin stated.
Dr. Gavin has been a chemistry professor at Iona since 1982. He holds a doctoral degree in chemistry from the State University of New York at Stony Brook and attended the State University of New York at New Paltz where he earned a B.A. degree. He and his family live in New Paltz.
Source: westchester.com
Posted under Alzheimer's disease, Clinical Trials, Discoveries, Innovations and Patents, Drug Development, Medicinal Chemistry, Natural Products, North America, Reports, Research Projects, USA and Canada | Comments Off
Study: Gene markers may aid prostate cancer test
Last Updated on Thursday, 16 December 2010 11:24 Written by Editor Thursday, 16 December 2010 11:22
The widely used blood tests measure a protein named PSA that only sometimes signals prostate cancer is brewing. It can be high for other reasons, but doctors order a biopsy to check for a tumor whenever PSA reaches a certain level.
Now scientists have discovered a set of genetic variants that show those cutoffs may be skewed for some men because their normal PSA level is naturally much higher than the average that PSA testing was based on.
That means “you end up biopsying a lot of prostates that did not need any biopsy,” said Dr. Kari Stefansson, chief executive officer of deCODE Genetics in Iceland.
His team reported the findings Wednesday in the journal Science Translational Medicine.
Stefansson said he plans to develop a test for those genetic markers, perhaps later next year, in hopes that doctors could use the information to customize how they read and react to their patient’s PSA test results.
This genetic approach makes sense but “I don’t think that this test is ready for prime time” without more research to confirm the findings, cautioned Dr. Otis Brawley, chief medical officer of the American Cancer Society, who wasn’t part of the study.
“It’s important, but it’s a small step in the long road ahead” for better prostate cancer detection, he said.
Making a PSA test more accurate solves only part of the problem, Brawley stressed. Screening often detects small prostate tumors that will prove too slow-growing to be deadly, but there’s no sure way to tell in advance who needs aggressive therapy.
“What we desperately need is some type of test … that tells us, ‘This is the kind of prostate cancer that kills’ versus the kind of cancer that doesn’t kill,” he said.
More than 190,000 cases of prostate cancer will be diagnosed this year in American men, and it will kill about 27,000. But routine screening is highly controversial: While most men over 50 have had at least one PSA test, many major medical groups don’t recommend them, worried they may do more harm than good. The cancer society, for instance, advises that men be told of the pros and cons and decide for themselves.
Among the problems: More than a third of men with PSA levels of 10 or more have no evidence of prostate cancer at biopsy, and many doctors order a tumor check at levels lower than that, around 4. Conversely, some men with very low PSA levels wind up with cancer.
Stefansson’s team discovered a set of genetic variants that alters how much PSA, or prostate specific antigen, men naturally produce.
The team reported that men who bear any of three of those variants had PSA levels about 40 percent higher than average men. When they examined the records of nearly 4,000 men in Iceland and Britain who underwent prostate biopsies, those high-PSA producers were more likely to have had an unnecessary biopsy.
Conversely, men with a fourth variant had PSA levels about 40 percent lower than average. Roughly 5 percent of men fall into each category, Stefansson said.
What does that mean? If a doctor usually orders a biopsy for a PSA of 4, a high-PSA producer might not need one until reaching almost 6, Stefansson said. But a low-PSA producer might need one sooner.
Source: physorg.com
Posted under Cancer Research, Oncology Research, Reports, Research Projects | Comments Off
Jet Lag Pill to Slow Down Body Clock
Last Updated on Thursday, 16 December 2010 10:57 Written by Editor Thursday, 16 December 2010 10:57
Scientists are one step closer to developing a jet lag pill that could relieve millions of long-haul passengers from sleepless nights and mid-afternoon drowsiness.
Using automated screening techniques developed by pharmaceutical companies to find new drugs, researchers from UC San Diego and three other research institutions have discovered a molecule with the most potent effects ever seen on the biological clock.
Dubbed “longdaysin,” for its ability to dramatically slow down the biological clock, the new compound could pave the way for a host of new drugs to treat severe sleep disorders or quickly reset the biological clocks of jet-lagged travellers who regularly travel across multiple time zones.
The researchers demonstrated the dramatic effects of longdaysin by lengthening the biological clocks of larval zebra fish by more than 10 hours.
“Theoretically, longdaysin or a compound like it could be used to correct sleep disorders such as the genetic disorder Familial Advanced Sleep syndrome, which is characterized by a clock that’s running too fast,” said Steve Kay, dean of UCSD’s Division of Biological Sciences, who headed the research team.
“A compound that makes the clock slow down or speed up can also be used to phase-shift the clock—in other words, to bump or reset the hands of the clock. This would help your body catch up when it is jet lagged or reset it to a normal day-night cycle when it has been thrown out of phase by shift work.”
Biologists in Kay’s laboratory and the nearby Genomics Institute of the Novartis Research Foundation, led by Tsuyoshi Hirota, the first author of the paper, discovered longdaysin by screening thousands of compounds with a robot that tested the reaction of each compound with a line of human bone cancer cells that the researchers genetically modified so they could see visually the changes in the cells” circadian rhythms.
This was done in the cells by attaching a clock gene to a luciferase gene used by fireflies to glow at night, so that the cells glowed when the biological clock was activated.
The robot screened more than 120,000 potential compounds from a chemical library into individual micro-titer wells—a system used by drug companies called high-throughput screening—and automatically singled out those molecules found to have the biggest effects on the biological clock.
Once Kay’s group had isolated longdaysin, they turned to biological chemists in Peter Schultz’s laboratory at The Scripps Research Institute to characterize the molecule and figure out how it lengthened the biological clock.
That analysis showed that three separate protein kinases were responsible for the dramatic effect of longdaysin, one of which, CK1alpha, had previously been ignored by chronobiology researchers.
The researchers then showed that longdaysin had the same effect of lengthening the biological clock in mouse tissue samples and in zebrafish larvae that carried luciferase genes attached to their clock genes.
Kay’s research team plans to test longdaysin on mice in the near future, but their goal isn’t to develop longdaysin into a drug. “Longdaysin is not as potent as we would like,” he adds. “This will be a tool for research.”
Source: The Times of India http://timesofindia.indiatimes.com/life-style/health-fitness/health/Jet-lag-pill-to-slow-down-body-clock/articleshow/7104145.cms#ixzz18HqNJo62
Posted under Cell Analysis, Compound Libraries, Compound Screening, Discoveries, Innovations and Patents, Drug Development, Research Projects | Comments Off
Nine U.S. Health Research Centers to Receive $255 Million
Last Updated on Tuesday, 27 July 2010 03:01 Written by admin Thursday, 22 July 2010 03:51
Nine health research centers have received funds to develop ways to reduce the time it takes for clinical research to become treatments for patients. The funds were awarded as part of the Clinical and Translational Science Awards (CTSA) program which is led by the National Center for Research Resources (NCRR), part of the National Institutes of Health.
“A critical goal of biomedical research is to transform discoveries into preventions, treatments, and cures,” said NIH Director Francis S. Collins, M.D., Ph.D. By working together, CTSAs are removing barriers to research, training new generations of clinical and laboratory research teams, and providing them with the equipment and resources they need.
Now in its fourth year, the CTSA consortium has generated resources that transform the research and training environment to enhance the efficiency and quality of clinical and translational research. Examples include a Web-based national recruitment registry that connects researchers with volunteers interested in participating in clinical studies, establishing public-private partnerships, and a portal that connects researchers with potential investigational drugs that may be useful in new ways.
The 2010 CTSAs expand consortium representation in new areas including New Mexico, Virginia and the District of Columbia, growing the consortium to 55 member institutions. The nine new institutions are:
Children’s National Medical Center, Washington, D.C.
Georgetown University with Howard University, Washington, D.C.
Medical College of Wisconsin, Milwaukee
University of California, Irvine
University of California, San Diego
University of Massachusetts, Worcester
University of New Mexico Health Sciences Center, Albuquerque
University of Southern California, Los Angeles
Virginia Commonwealth University, Richmond
View descriptions of these CTSA awardees at www.ncrr.nih.gov/ctsa2010.
“The nine institutions that have received CTSAs this year extend the geographic reach of the consortium and bring additional talent and expertise in such areas as children’s health, outreach to underrepresented communities, and systems to share research information,” said NCRR Director Barbara Alving, M.D.
The CTSA consortium now includes awardees in 28 states and the District of Columbia. When the program is fully implemented in 2011, it will support approximately 60 CTSAs across the nation.
A sixth and final funding opportunity announcement for CTSAs is available, calling for the next round of applications to be submitted by Oct. 14, 2010, with the awards expected in July 2011. For more information about this funding announcement, see www.ncrr.nih.gov/crfunding.
For more information about the CTSA program, visit www.ncrr.nih.gov/ctsa. The CTSA consortium website, which provides information on the consortium, current members and new grantees, can be accessed at www.CTSAweb.org.
The National Center for Research Resources (NCRR), a part of NIH, provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation. For more information, visit www.ncrr.nih.gov.
The National Institutes of Health (NIH) The Nation’s Medical Research Agency includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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TimTec Launches Division of Organic Synthesis and Medicinal Chemistry Contract Research Services
Last Updated on Saturday, 24 July 2010 04:31 Written by admin Thursday, 8 July 2010 11:39
Newark, DE, July 8, 2010 Press Release – TimTec, LLC is pleased to announce the launching of the new Division that manages Organic Synthesis and Medicinal Chemistry Contract Research Services. The emergence of the division is an evolutionarily progression for TimTecs business development. The company has been known for its expertise in organic chemistry design and supply for drug discovery for 15 years. TimTec scientists have a proven track record of providing high quality services and showing outstanding integrity to their clients.
The Head of Contract Research Services, J. C. Pelletier, PhD., has over 20 years of research experience in the US pharmaceutical industry as a hands-on medicinal chemist and project Team Leader at large companies and smaller, start-up operations. The TimTec contract research team consists of experienced, bench level scientists who have access to state of the art synthesis, analytical and quality control facilities. TimTec specialists are keenly aware of all the intricate details and chemistry challenges that go into bench-top research before a qualified lead molecule emerges.
TimTec remains flexible in delivering practical chemistry solutions molded to custom research requirements and budgets. Contract research services include, but are not limited to, flexible contracts, program management, structure-activity relationship evaluation, lead optimization, property optimization for ADME and PK, metabolite synthesis, enabling technologies (parallel synthesis, multistep synthesis, analytical chemistry), mg to kg synthesis capacity, compound distribution, and patent application preparation assistance. The Contract Research Division puts great emphasis on speed, real-time feedback, ongoing communication, superior compound quality, and the protection of clients knowledge resources and interests. Dedication to service is matched by exceptionally competitive prices.
Contact Information:
TimTec LLC
Harmony Business Park A-301
Newark DE 19711
Tel 302 292 8500
Fax 302 292 8520
info@timtec.net
http://www.timtec.net/contract-research-services.html
About TimTec
TimTec LLC is a privately held company located in Newark Delaware, USA. It was founded in 1995 and began its work in the areas of acquisition and distribution of synthetic organic and natural compounds and collections, custom synthesis, and laboratory equipment to become a full service partner for drug discovery. TimTec has established a global network of thousands of scientists from research centers around the world. International customers include major pharmaceutical, biotech, agricultural, and educational companies and institutions, which use TimTec products for research and development programs.
Posted under ADMET Studies, Business and Investment, Drug-Like Compounds, North America, Press Releases, R & D, Research Projects | Comments Off
Molecular Templates and ImClone Systems Form Oncology Drug Discovery and Translation Research Collaboration
Last Updated on Thursday, 8 July 2010 10:36 Written by admin Thursday, 8 July 2010 10:36
GEORGETOWN, Texas, Jul 06, 2010 (BUSINESS WIRE) — Molecular Templates announced today that it has entered into a collaborative oncology drug discovery and translation research agreement with ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company.
Under the terms of the agreement, Molecular Templates will identify Engineered Toxin Bodies (ETBs) against an undisclosed oncology target of interest selected by ImClone. ImClone will conduct preclinical studies utilizing the ETBs to evaluate their therapeutic potential in oncology. Upon completion of the evaluation of the ETBs, Molecular Templates and ImClone have the option to continue exclusive development of selected ETBs by ImClone for potential commercialization by Lilly. Molecular Templates will receive upfront, milestone and royalty payments if any of the ETBs are selected for further development and commercialization. Financial terms of the agreement were not disclosed.
“We are excited to partner with a premier biologics innovator like ImClone,” said Eric Poma, president and chief executive officer of Molecular Templates. “We look forward to collaborating with ImClone to identify novel oncology therapies by leveraging our ETB technology. Given ImClone’s depth in the oncology and biologics arena, we view this partnership as validation of our novel platform and its potential to be used to discover and develop the next generation of targeted biologic medicines.”
ETBs represent a new class of small biologic therapeutics derived from modified bacterial toxins that retain the potent direct cell-kill properties, internalization capabilities, and predictable pharmacokinetics of the parent toxins, but have significantly reduced immunogenicity. These features confer a host of advantages over traditional biologic and small molecule approaches and allow for discovery of therapeutic targets that may be uniquely accessible by ETBs. Molecular Templates has created a vast library (>10(15)) of ETBs, each with distinct binding affinities that can be directly screened for cell-kill ability to rapidly identify promising therapeutic candidates based on both specificity and efficacy to a given target.
About ImClone Systems
ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, is committed to advancing oncology care by developing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. Additional information about ImClone is available at www.imclone.com.
About Molecular Templates
Molecular Templates is a private biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a next generation targeted biologics platform. Using the Direct Select Platform (DSP), Molecular Templates has created ETBs libraries that can be screened in a high throughput manner to identify novel therapeutic targets and molecules for various disease states. Molecular Templates plans to identify and develop therapeutics through partnerships with select biopharmaceutical companies as well as on its own. The company completed a series A financing in 2009 led by Sante Ventures. For more information, visit www.moleculartemplates.com.
SOURCE: Molecular Templates
Posted under Collaborations, North America, Press Releases, Research Projects | Comments Off
TimTec’s Contract Research Services
Last Updated on Thursday, 8 July 2010 10:18 Written by Editor Thursday, 8 July 2010 03:22
High Quality Organic Synthesis and Medicinal Chemistry Contract Research Services at an Outstanding Value
TimTec brings 15 years of expertise in organic chemistry design and supply for drug discovery closer to your supplemental bench-top requirements by launching The Organic Synthesis and Medicinal Chemistry Contract Research Services Division. TimTec scientists have a proven track record of providing high quality services and showing outstanding integrity to their clients.
TimTec remains flexible in delivering practical chemistry solutions molded to custom research requirements and budgets. All Contract Research Services are delivered with an emphasis on speed, real-time feedback, ongoing communication, superior compound quality, and the protection of our clients’ knowledge resources and interests. We are dedicated to providing these services at exceptionally competitive prices.
The Head of Contract Research Services has over 20 years of research experience in the US pharmaceutical industry as a hands-on medicinal chemist and project Team Leader at large companies and smaller, start-up operations. We are keenly aware of all the intricate details and chemistry challenges that go into bench-top research before a qualified lead molecule emerges. Your TimTec contract research team consists of experienced, bench level scientists who have access to state of the art synthesis, analytical and quality control facilities.
TimTec Contract Research Services Start with:
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Flexible Contracts
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Program Management
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State of the Art Facilities
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Structure-Activity Relationship Evaluation
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Lead Optimization
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Property Optimization for ADME and PK
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Metabolite Synthesis
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Enabling Technologies – Parallel synthesis, multistep synthesis, analytical chemistry
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Mg to Kg Capacity
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Compound Distribution – Solid or solution, vials or plates
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Patent Application Preparation Assistance
Supplemental Services and Products:
Custom Synthesis
Compound Acquisition
Weighting and Plating
HTS compounds and compound collections – ActiMol Line of products
Posted under ADMET Studies, Drug-Like Compounds, Medicinal Chemistry, New Products, North America, R & D, Research Projects | Comments Off
SGX Pharmaceuticals Announces Strategic Collaboration To Develop And Commercialize BCR-ABL Inhibitor
Last Updated on Thursday, 13 May 2010 10:22 Written by Editor Thursday, 13 May 2010 10:22
Under the terms of the agreement, SGX will receive from Novartis $25 million in upfront payments and the purchase of SGX common stock. Along with success-based milestones, but excluding royalties, total payments to SGX could exceed $515 million, including a minimum of two years of research funding.
The success of Gleevec(TM) (imatinib), the first targeted therapy in Philadelphia Positive (Ph+CML) proven to inhibit BCR-ABL, has fundamentally changed the treatment of Ph+CML. However, a subset of patients develops resistance to Gleevec or cannot tolerate therapy. For these patients there are currently no other approved treatment options. Drug candidates from SGX’s lead series, developed from its FAST(TM) proprietary drug discovery platform, have exhibited activity against wild-type and drug resistant BCR-ABL mutants, including the most challenging T315I mutant.
“Novartis is the leader in developing novel targeted therapies to treat CML,†said Mike Grey, president and chief executive officer of SGX Pharmaceuticals. “With their extensive experience developing and commercializing Gleevec as well as development of the novel investigational compound, nilotinib/AMN107, we believe they are the ideal partner with whom to develop our series of next-generation BCR-ABL inhibitors. This is a tremendous validation of our FAST technology for generation of novel lead molecules for key therapeutic targets.â€
Background on the Agreement
SGX will be responsible for completing preclinical development of the lead candidate and submitting an Investigational New Drug application with the Food and Drug Administration. SGX will also be responsible for the completion of an initial phase I clinical study, after which time Novartis will be responsible for conducting further clinical development and commercialization of the compound.
In addition to the upfront and milestone payments, SGX will receive royalty payments upon successful commercialization of products developed under the collaboration. SGX retains an option to co-commercialize, in the U.S., oncology products developed under the agreement. If exercised, the option would enable SGX to reinforce the commercial presence in the North American hematology markets which the company plans to establish with the potential launch of Troxatyl(TM) in the second half of 2007, assuming the successful completion of the ongoing Phase II/III clinical trial for the treatment of third-line acute myelogenous leukemia and regulatory approval of Troxatyl for this initial indication in 2007.
Background on CML: Prognosis and Treatments
Chronic myelogenous leukemia is a malignant cancer of the bone marrow causing rapid and abnormal growth of white blood cells. According to the National Institutes of Health, approximately 4,600 new cases of CML are diagnosed annually, accounting for 7 to 20 percent of leukemia cases. CML is associated with a chromosome abnormality called the Philadelphia chromosome. Since its approval in 2001, Gleevec has become the standard of care for Ph+ CML. Results from the IRIS study (International Randomized Interferon versus STI571), the largest clinical trial to date for newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, show that 90.3 percent of patients who were initially randomized to take Gleevec were still alive after 54 months.
The prevalence of CML has increased substantially because Gleevec therapy makes it possible for patients with CML to live with the disease much longer than possible with previously used treatments. Gleevec works directly on leukemic cells by inhibiting the action of BCR-ABL tyrosine kinase, the enzyme responsible for uncontrolled growth of leukemic cells. Despite this clinical success, resistance to Gleevec has emerged in a subset of patients. Once patients lose response to optimized doses of Gleevec, the only currently approved treatment is bone marrow transplantation preceded by high-dose chemotherapy and radiation, for which many CML patients are not eligible.
“We believe that a BCR-ABL inhibitor developed through this collaboration could have the potential to be used both as a monotherapy in second-line treatment of refractory or relapsed CML, and in combination with Gleevec or another agent in first-line treatment of CML,†added Dr. Stephen Burley, chief scientific officer of SGX Pharmaceuticals.
About: FAST, short for Fragments of Active Structures, is SGX’s proprietary fragment-based drug discovery platform for rapid identification of novel, potent and selective small molecule inhibitors of drug targets. FAST addresses many of the limitations of traditional approaches utilized by large pharmaceutical companies to find lead compounds, making it an attractive technology for targets that have not yielded promising leads from high-throughput screening.
FAST is based on a proprietary fragment library of approximately 1,000 structurally diverse, low molecular weight compounds. FAST integrates a series of technologies, including:
* A high-throughput capability to generate many different crystal structures of a target protein in parallel;
* The evaluation of the library of fragments and direct visualization of bound fragments utilizing X-ray crystallography; and
* The use of novel computational and structure-based design methods and iterative synthetic chemistry to optimize these fragments into drug candidates.
SGX believes these combined technologies generate an efficient platform for drug discovery that delivers lead compounds active against a wide range of targets, while accessing high chemical diversity and the potential for good drug-like properties.
About: SGX Pharmaceuticals is a biotechnology company focused on the discovery, development and commercialization of innovative cancer therapeutics. The Company’s lead product candidate, Troxatyl(TM), is currently being evaluated in a pivotal phase II/III trial for the treatment of third-line acute myelogenous leukemia, an indication for which there is currently no approved therapy or standard of care. SGX has developed a pipeline of oncology drug candidates based on its enabling, proprietary FAST(TM) drug discovery platform, including a portfolio of next generation BCR-ABL inhibitors. FAST allows for the rapid identification of novel, potent and selective small molecule compounds for well validated but challenging targets.
source: biotechconnection.com
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Eli Lilly and GlaxoSmithKline: A Tale of Two Different Pharmas
Last Updated on Saturday, 24 July 2010 04:09 Written by Editor Wednesday, 12 May 2010 01:10
New models for drug development, especially in big pharma, are being experimented by different companies. Eli Lilly (LLY) and GlaxoSmithKline (GSK) have two different models. These models do not throw out the old ones – but do offer additional routes going forward.
Lilly has a Phenotypic Drug Discover Initiative, (or PD2), launched in 2009. Lilly solicits compounds from other companies so long as they are in certain therapeutic areas (oncology, diabetes, osteoporosis, and Alzheimer’s Disease). Compound structures are sent to Lilly electronically where they are evaluated using modeling and simulation. If the compound passes the screen, the physical compound is sent to Lilly for further testing. If the compound passes the physical test, the fun begins.
All testing by Lilly is free and IP remains with the originating company or institution. What Lilly gets in return is the first right to exclusively negotiate an agreement. If talks break down, the originator keeps all the data generated by Lilly.
Having had some personal experience through my biotechnology company (IMC Biotechnology), I think this is a very interesting approach. We submitted 9 compounds to Lilly and one of them went through the screening process. The software had some minor glitches but the Lilly representatives were very helpful in addressing those glitches.
I think this is a great way for Lilly to expand its repertoire of compounds beyond those invented by its chemists. Certainly one way of going beyond the NIH (not invented here) syndrome.
GSK has come up with an opposite approach where it is offering its library of compounds to researchers in a certain therapeutic area (under-served tropical diseases). For example, it is offering 13,500 compounds that appear to work in malaria. GSK will let other scientists try to develop malaria drugs — free from royalties or other payments to GSK. They were narrowed down from more than 2 million compounds.
More unusual is its open lab project. GSK plans to give up to 60 outside scientists from around the globe access to what it called the “Open Lab,” at an existing company research lab in Spain. Researchers from universities, foundations, etc will be able to use the facilities to try to develop new medicines for diseases plaguing poor countries.
GSK is to start a foundation to fund research and idea sharing, kicking in $8 million initially. It also plans to work with the Emory Institute for Drug Discovery. I have worked a bit with the Emory Institute of Drug Discovery and know they have an excellent drug development team, but have not learnt anything from them about what their exact role in this project is going to be.
While a small fraction of overall R&D efforts, it nevertheless is a significant departure from business as usual. And while GSK does not expect to get royalties, the halo effect, especially with health care reform in the spotlight, cannot be neglected. One could criticize GSK in pointing out that the company does not have much to lose by sharing data in neglected diseases – and that it is not doing so in the more lucrative markets such as oncology. But I doubt that the millions of patients suffering from malaria and TB will support such criticism. New models for drug development, especially in big pharma, are being experimented by different companies. Eli Lilly and GlaxoSmithKline have two different models. These models do not throw out the old ones – but do offer additional routes going forward.
So the two companies have differing strategies that actually could be quite synergistic. Maybe it is time to pay the ultimate compliment and copy each other.
source: seekingalpha.com
Posted under Business and Investment, Collaborations, Compound Screening, Discoveries, Innovations and Patents, Press Releases, Research Projects | Comments Off
SCYNEXIS, Inc. Receives Milestone Payment From Collaboration With Merck & Co., Inc.
Last Updated on Wednesday, 5 May 2010 10:43 Written by Editor Wednesday, 5 May 2010 10:43
RESEARCH TRIANGLE PARK, NC — 12/17/09 — Drug discovery and development company SCYNEXIS, Inc. announced today that it has achieved a third milestone in its collaboration with Merck & Co., Inc. to develop novel antifungal agents. This latest milestone payment was triggered following the initiation of clinical development for a compound derived from the program.SCYNEXIS and Merck initiated the antifungal agent discovery and development program in 2002. SCYNEXIS contributed medicinal chemistry, computational chemistry, bioanalytical and ADMET support to this program. Merck is responsible for development once compounds are accepted as pre-clinical candidates. Under the terms of the collaboration, SCYNEXIS is eligible to receive additional milestone payments and up to double-digit percentage royalties on worldwide sales of any product resulting from the program.
“SCYNEXIS is pleased to reach this important clinical milestone in collaboration with our valued partner, Merck,” noted Yves Ribeill, Ph.D., President and Chief Executive Officer of SCYNEXIS. “This is the eleventh time in SCYNEXIS’ ten year history that a compound originating from our discovery platform has advanced into the clinic — an accomplishment we believe speaks strongly to the strength of our capabilities.”
About SCYNEXIS
SCYNEXIS is a premier drug discovery and development company headquartered in Research Triangle Park, N.C. SCYNEXIS’ mission is to be the leader in delivering effective and innovative drug pipeline solutions to its pharmaceutical partners.
SCYNEXIS research teams integrate medicinal chemistry, advanced biological screening, ADMET-PK, bioanalysis and analytical chemistry, process chemistry, cGMP API manufacturing, and use powerful, proprietary technologies such as the HEOS® Software Suite and MEDCHEM-FACTORY® to advance molecules to candidate selection. The fully integrated research and development teams at SCYNEXIS have been tailored to be especially effective in moving customer projects from the discovery phase to the clinic. www.scynexis.com
For further information, please contact:
SCYNEXIS, Inc.
Terry Marquardt
Executive Director, Market Development & Communications
Email Contact
Tel: +1-919-544-8603
SCYNEXIS Media Contacts:
Rick Rountree
Rick Rountree Communications, Inc.
Email Contact
Tel. +1 919-878-1144
Sarah Cavanaugh
MacDougall Biomedical Communications
Email Contact
Tel. +1 781-235-3060
Source: earthtimes.org
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Karwar scientist’s theory to ‘weed’ out CO2
Last Updated on Thursday, 28 January 2010 06:05 Written by Editor Thursday, 28 January 2010 06:05
KARWAR: While representatives of 192 countries are engaged in climate change debates at Copenhagen, Dr Ullas Naik, a marine scientist at the department of marine biology, at Karnatak University’s PG Centre, here has suggested the unassuming sea weed as a possible cure to the planet’s ills.Calling for the scientific culture of algae, commonly known as sea weed and its conservation and protection, Naik points out that these algae provide much of the earth’s oxygen. They absorb carbon dioxide from the environment and carry out photosynthesis to enhance the productivity.Naik, who presented a paper on his findings at a seminar at the university recently, says the discovery has shown that these marine weeds have a remarkable ability to detoxify serious organic pollutants such as TNT or polycyclic aromatic hydrocarbons.According to him, these algae have an intrinsic ability to detoxify TNT 5-10 times faster than any known terrestrial plant.Since some of the marine organisms, particularly marine invertebrates like clamps, shrimp, oyster or crab, the staple food for many, tend to accumulate toxins, growth of sea weeds will have important implications for sea food safety, he asserts.Marine algae contain protein (5- 10%), fat (0.5-1.5%), ash (10-18%), fibre (3-6%) and carbohydrates (40-60%). He says they are rich in minerals and vitamins and can be used as food.The bioactive compound found in seaweeds have variety of applications in pharmaceutical field. Naik says attempts should be made for screening pharmaceutically active compounds from seaweeds. In fact, seaweeds will be the medicinal food of this century, Naik opines.Cautioning that these “wonderful marine species’’ should be explored scientifically, he says they can be used as manure and fodder.
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Aeolus Drug Protects the Gastrointestinal Tract in Acute Radiation Syndrome Studies Sponsored by the National Institutes of Health`s National Institute for Allergy and Infectious Diseases
Last Updated on Wednesday, 2 December 2009 12:12 Written by Editor Wednesday, 2 December 2009 12:12
* AEOL 10150 Effectively Increases Regeneration of GI Stem Cells and Reduces the
Severity and Duration of Diarrhea
* Drug Improves Survival When Administered 24 Hours after Total Body
Irradiation
MISSION VIEJO, Calif.--(Business Wire)--
Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) announced today that recent
experiments in preclinical models conducted by the National Institutes of
Health`s (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
Radiation/Nuclear Medical Countermeasure Development program have shown that
AEOL 10150 can effectively increase regeneration of gastro-intestinal (GI) stem
cells, reduce the severity and duration of diarrhea and improve survival when
administered at 24 hours after doses of total-body irradiation that produce the
lethal GI syndrome. There are no published studies of agents that accomplish
this enhanced stem cell regenerative effect while maintaining GI function and
improving survival when administered post irradiation.
"The Aeolus drug AEOL 10150 passed our first phase of rigorous testing and
showed definitive effects on crypt stem cells and other secondary parameters
used to assess drug efficacy in ameliorating the acute GI syndrome," stated
Catherine Booth, Ph.D., Managing Director, Contract Research Services at
Epistem, Ltd. "This is one of few drugs shown to affect 'both' stem cell crypt
regeneration and survival in a syndrome that heretofore has been resistant to
mitigation with drugs administered at 24 hours post lethal exposure."
NIAID has a contract with the University of Maryland to provide product
development support services for the development of countermeasures against
radiation exposure. These studies are being conducted by Epistem, a
subcontractor of the University of Maryland, in compliance with criteria of the
FDA that are a pre-requisite for movement of the Aeolus drug along the pathway
for FDA licensure to treat lethally irradiated persons in the event of a
terrorist nuclear act. Epistem operates a major contract research organization
and provides services to identify novel drugs that can protect or improve the
repair of the gastrointestinal (GI) tract following exposure to irradiation and
performed these studies as part of its US NIH`s program for the screening of a
novel agents for bio-defense applications.
The NIH NIAID Radiation/Nuclear Medical Countermeasure Development program leads
the U.S. effort to develop treatments for radiation sickness following a nuclear
terrorist attack. GI-ARS is a massive, currently untreatable, problem following
high-dose, potentially lethal radiation exposure. Agents that mitigate these
effects would reduce sickness and hopefully prevent fatalities. The tests
performed by NIH/NIAID are also likely to identify agents with oncology
supportive care applications - agents that will reduce the severe ulceration and
diarrhea (mucositis) experienced by patients during radio- and chemo-therapy.
Risk of injury to the intestine is dose-limiting during abdominal and pelvic
radiation therapy-interventions that limit post-irradiation intestinal
dysfunction would have significant impact in large number of patients, estimated
to be between 1.5 to 2 million cancer survivors with post-irradiation intestinal
dysfunction. AEOL 10150 has previously demonstrated protective effects in
protecting healthy normal cells from damage occurring due to cancer radiation
therapy in preclinical models.
Radiation Damage to the GI Tract
The intestinal epithelium, a single layer of cells lining the surface of the GI
lumen, is responsible for vital functions of nutrient absorption, maintaining
fluid and electrolyte balance and protection of the body from bacteria,
bacterial toxins and non absorbed materials. The functional integrity of the GI
system is maintained via incessant production of epithelial cells from
specialized stem cells located in crypts at the base of the epithelium.
High-dose, total-body irradiation can result in a lethal GI syndrome that
results in significant morbidity and mortality within days consequent to killing
of the crypt stem cells and loss of the protective and absorptive epithelial
barrier. There are no FDA-approved drugs or biologics to treat the acute GI
syndrome.
About AEOL 10150
AEOL 10150 is a small molecule that catalytically consumes reactive oxygen and
nitrogen species (free radicals). The compound is a manganoporphyrin that
contains a positively-charged manganese metal ion that is able to accept and
give electrons to and from reactive oxygen species ("ROS") and reactive nitrogen
species ("RNS"). Research has shown that ROS and RNS have important cell
signaling roles, and through its interaction with RNS and ROS, AEOL 10150
appears to have multiple mechanisms of action including anti-oxidant,
anti-inflammatory and anti-angiogenic activities. In preclinical studies AEOL
10150 has demonstrated reductions in the markers for tissue hypoxia,
angiogenesis, inflammation and oxidative stress. Specifically, AEOL 10150 is
able to down-regulate oxidative stress and severe inflammation, which is
responsible for much of the tissue destruction that occurs as a result of
radiation exposure.
AEOL 10150 offers several unique advantages as a countermeasure for the
treatment of ARS, mustard gas and chlorine gas for civilian and military
populations. These include:
-- Flexible Treatment Paradigm - AEOL 10150 is intended for the treatment of
patients post-exposure, even in those who are already exhibiting symptoms,
eliminating the need for immediate administration in a predefined treatment
window. This approach has the added benefit of not requiring biodosimetry (a
means of laboratory analysis of the blood to determine the level of radiation
exposure).
-- Advanced Development Stage - AEOL 10150 has demonstrated safety in three
human clinical trials, and has an extensive pre-clinical safety and toxicology
package completed. The product also has an established stability profile that
permits long-term storage.
-- Large scale manufacturing - Aeolus has contract capacity with a large
manufacturing site to mass produce large quantities of AEOL 10150 under GMP
conditions.
-- Multiple Applications - AEOL 10150 has demonstrated protective effects
against radiation and mustard gas exposure, and within these indications has
shown the ability to treat multiple organ systems.
-- Commercial Application - Additionally, AEOL 10150 is being developed for use
as an adjunct to cancer radiation therapy, and preclinical data suggest that the
compound protects healthy normal cells from the effects of radiation without
compromising the efficacy of the radiation in killing tumor cells.
Potential for AEOL 10150 as a Countermeasure Against Multiple Terrorist Threats
AEOL 10150 has shown significant protective effects against radiation and
mustard gas in preclinical models. Additionally, based on its mechanism, it is
believed that the compound may potentially protect against exposure to chlorine
gas. Studies have been initiated to further explore AEOL 10150`s ability to
protect the lungs from damage due to exposure to mustard gas and chlorine gas. A
compound with the potential to protect against multiple threats would be of
significant benefit in both the military and civilian efforts to protect
citizens against potential threats. The FDA has a special rule under which
compounds may be approved for use against chemical and nuclear threats on the
strength of preclinical efficacy studies, which allows the potential for an
accelerated approval path versus conventional pharmaceutical applications.
About Aeolus Pharmaceuticals
Aeolus is developing a variety of therapeutic agents based on its proprietary
small molecule catalytic antioxidants, with AEOL 10150 being the first to enter
human clinical evaluation. AEOL 10150 is a patented, small molecule catalytic
antioxidant that mimics and thereby amplifies the body`s natural enzymatic
systems for eliminating reactive oxygen species, or free radicals. Studies
funded by the National Institutes for Health are currently underway evaluating
AEOL 10150 as a treatment for exposure to radiation, mustard gas and chlorine
gas. Additionally, the Company has funded mouse and non-human primate studies
necessary to seek approval of the compound as a treatment to protect and/or
mitigate radiation-induced damage to the lungs for which there are no
FDA-approved drugs. Radiation-induced pneumonits and/or fibrosis are potentially
lethal delayed effects of acute radiation exposure. The ability to control these
delayed consequences will also translate into the clinic and further emphasize
the dual utility of AEOL 10150.
About Epistem, Ltd.
Epistem is a biotechnology company commercializing its expertise in epithelial
stem cells in the areas of oncology, gastrointestinal diseases and
dermatological applications. Epistem develops innovative therapeutics and
biomarkers and provides contract research services to drug development
companies. The Group`s expertise is focused on the regulation of adult stem
cells located in epithelial tissue, which includes the gastrointestinal tract,
skin, hair follicles, breast and prostate. Epistem does not conduct research in
the areas of embryonic stem cells or stem cell transplantation. Epistem operates
three distinct business divisions, Contract Research Services, Novel Therapies
and Biomarkers.
Epistem`s Contract Research Services division provides scientific expertise and
preclinical research models to the NIH`s research programme on Radiation/Nuclear
Medical Countermeasure Development. This research programme, funded by the
National Institute of Allergy and Infectious Diseases through a contract with
the University of Maryland School of Medicine, tests drugs from early screening
through advanced development for the prevention and treatment of radiation
sickness following exposure to high dose radiation following a nuclear terrorist
attack. Epistem has developed its proprietary models to provide a unique insight
into the mechanisms of intestinal damage and repair following radiation
exposure. Epistem`s models evaluate the efficacy, mechanism of action, optimal
drug dosing and scheduling of potential new treatments. Epistem has an
eight-year track record of providing testing services to over 130 international
company clients in the United States, Europe, and Japan.
The statements in this press release that are not purely statements of
historical fact are forward-looking statements. Such statements include, but are
not limited to, those relating to Aeolus` product candidates, as well as its
proprietary technologies and research programs. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
Aeolus` actual results to be materially different from historical results or
from any results expressed or implied by such forward-looking statements.
Important factors that could cause results to differ include risks associated
with uncertainties of progress and timing of clinical trials, scientific
research and product development activities, difficulties or delays in
development, testing, obtaining regulatory approval, the need to obtain funding
for pre-clinical and clinical trials and operations, the scope and validity of
intellectual property protection for Aeolus` product candidates, proprietary
technologies and their uses, and competition from other biopharmaceutical
companies. Certain of these factors and others are more fully described in
Aeolus` filings with the Securities and Exchange Commission, including, but not
limited to, Aeolus` Annual Report on Form 10-K for the year ended September 30,
2008. Readers are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date hereof.
Aeolus Pharmaceuticals, Inc.
John L. McManus
President and Chief Executive Officer
1-949-481-9825
Source: reuters.com
Copyright Business Wire 2009
Posted under Collaborations, Discoveries, Innovations and Patents, Drug Development, New Products, Press Releases, Research Projects, Stem Cell Research | Comments Off
Scripps research scientists take step in stem cell work
Last Updated on Tuesday, 1 December 2009 12:59 Written by Editor Tuesday, 1 December 2009 12:59
A team led by scientists from The Scripps Research Institute has developed a method that dramatically improves the efficiency of creating stem cells from human adult tissue, without the use of embryonic cells. The research makes great strides in addressing a major practical challenge in the development of stem-cell-based medicine.
The findings were published in an advance, online issue of the journal Nature Methods on Sunday.
The new technique, which uses three small drug-like chemicals, is 200 times more efficient and twice as fast as conventional methods for transforming adult human cells into stem cells (in this case called “induced pluripotent stem cells” or “iPS cells”).
“Both in terms of speed and efficiency, we achieved major improvements over conventional conditions,” said Scripps Research Associate Professor Sheng Ding, Ph.D., who led the study. “This is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating iPS cell research significantly.”
In addition to its significant practical advantages, the development of the technique deepens the understanding of the biology behind the transformation of adult human cells into stem cells.
The hope of most researchers in the field is that one day it will be possible to use stem cells – which possess the ability to develop into many other distinct cell types, such as nerve, heart, or lung cells – to repair damaged tissue from any number of diseases, from Type 1 diabetes to Parkinson’s disease, as well as from injuries. The creation of iPS cells from adult cells sidesteps ethical concerns associated with the use of embryonic stem cells, and allows the generation of stem cells matched to a patient’s own immune system, avoiding the problem of tissue rejection.
The creation of human iPS cells was first announced in December 2007 by two labs, one in Japan and another in Wisconsin. In both cases, the teams used viruses to insert multiple copies of four genes (eg. c-Myc, Oct4, Sox2, Klf4) into the genome of skin cells. These four genes then produced transcription factors turning on and off other genes, and pushing the cell to “dedifferentiate” into stem cells.
While the work was a major breakthrough, it left two major challenges for the field to solve before iPS cell therapy could be considered of any potential practical use. The first involved safety, since the technique relied on potentially harmful genetic manipulation, and worse yet, the insertion of two known cancer-causing genes (c-Myc and Oct4). The second problem was the length and inefficiency of the iPS cell process, which had a success rate of roughly one in 10,000 cells and took about four weeks from start to finish.
Ding and colleagues essentially solved the first problem, the reliance on genetic manipulation, earlier this year in a paper published in Cell Stem Cell (Volume 4, Issue 5, May 8, 2009). In the paper, the researchers demonstrated that they could use purified proteins to transform adult cells all the way back to the most primitive embryonic-like cells, avoiding the problems associated with inserting genes.
In the current paper, the team makes major strides in solving the second problem, efficiency.
In developing the improved method, Ding drew on his knowledge of biology. He decided he would focus his efforts on manipulating a naturally occurring process in cells, in particular in a type of adult cell called fibroblasts, which give rise to connective tissue.
This naturally occurring process – called MET (mesenchymal to ephithelial cell transition) – pushes fibroblasts closer to a stem-cell-like state. If he could manipulate such a fundamental process to encourage MET and the formation of stem cells, Ding reasoned, such a method would be both safer and more direct than hijacking other aspects of biology, for example those directly involved in cancer.
“People have studied this mechanism for 10 to 20 years,” said Ding. “It is a fundamental mechanism.”
Ding and colleagues tested a number of drug-like molecules, looking for those that inhibited the TGFï¢ (transforming growth factor beta) and the MEK (mitogen-activated protein kinase) pathways, which are known to be involved in the MET process. The researchers identified the most active compounds, then looked at their effects on stem cell creation when used singly and in combination.
The researchers found two chemicals – ALK5 inhibitor SB43142 and MEK inhibitor PD0325901 – used in combination were highly effective in promoting the transformation of fibroblasts into stem cells.
“This method is the first in human cells that is mechanism-specific for the reprogramming process,” said Ding.
And the two-chemical technique bested the efficiency of the classic genetic method by 100 times.
Efficient, Fast, Safe
But the researchers thought they might be able to do even better.
Attempting to increase the efficiency of the process even further, the team decided to enlist another natural pathway, the cell survival pathway. After screening a library of compounds targeting this pathway, the team focused on a novel compound called Thiazovivin.
The researchers found that a technique using Thiazovivin in combination with the two previously selected chemicals, SB43142 and PD0325901, beat the efficiency of the classic method by 200 times.
In addition, while the classic method required four weeks to complete, the new method took two weeks.
In addition to its virtues of speed and efficiency, Ding emphasizes that the safety profile of the new method is highly promising. Not only is the method based on natural biological processes, he said, but also the type of molecules used have all been tested in humans.
In addition to Ding, the article, “A Chemical Platform for Improved Induction of Human iPS Cells,” was authored by Tongxiang Lin (first author), Rajesh Ambasudhan, Xu Yuan1, Wenlin Li, Simon Hilcove, Ramzey Abujarour, Xiangyi Lin, and Heung Sik Hahm of Scripps Research, and Ergeng Hao and Alberto Hayek of The Whittier Institute for Diabetes, University of California San Diego.
The research was supported by the National Institutes of Health and Fate Therapeutics.
Source: lajollalight.com
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