Bio Screening Industry News

* 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

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 TGF (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

Scientists are a big step closer to their long-term of goal of creating patient-specific stem cells that are safe to use and don’t require the destruction of embryos.

Induced pluripotent stem cells – also known as iPS cells – are all the rage in the nascent field of regenerative medicine. Like embryonic stem cells, they have the potential to become any type of cell in the body and could be used to grow replacement parts, such as insulin-producing beta cells for diabetes patients or nerve cells for repairing spinal cord injuries.

Even better, they can be made by reprogramming skin or other cells from the patients who need them. That not only eliminates the need to use embryos, it ensures that the replacement tissues made from iPS cells are genetically matched to patients and won’t be rejected by the body’s immune system.

But there’s still a big catch: In order to rewind adult cells to a pluripotent state, researchers have to turn on a set of dormant genes that have the potential to cause tumors. So do the viruses they use to activate those genes.

So researchers have been looking for ways around this problem. One approach is to snip out the genes and viruses once the reprogramming is complete. Another is to use DNA sequences called transposons in place of viruses, then delete the transposons after they’re no longer needed. One group of researchers has even used genetic engineering to modify the key genes so that they can enter the skin cells without requiring viruses or transposons.

But many scientists think the safest approach is to replace the genes altogether with so-called small molecules. In a study published online today in the journal Cell Stem Cell, researchers from the Harvard Stem Cell Institute report that a single compound they dubbed RepSox can replace two of the four key reprogramming genes.

“We’re halfway home, and remarkably we got halfway home with just one chemical,” senior author Kevin Eggan, a professor in Harvard’s department of stem cell and regenerative biology, said in a statement.

Eggan’s team identified RepSox by screening 200 compounds and waiting a couple of weeks to see which of them did the best job of transforming mouse cells into iPS cells in combination with three of the four reprogramming genes. The researchers were surprised to find that their compound not only replaced the gene Sox2 (hence the name RepSox), but also made the gene c-Myc obsolete.

Now the group will turn its attention to finding other small molecules that could replace the remaining genes – Oct4 and Klf4 – as well, “opening a route to purely chemical programming,” they write.

EVRY, France, March 19 /PRNewswire/ –     Four research teams of I-STEM[*] have joined forces in a collaborative project that has just achieved a first pilot therapy-oriented screen of compounds and RNA interference aiming at reversing the altered phenotypes observed in human embryonic stem cells carrying the mutant gene for myotonic dystrophy type1. This assay inaugurates a series of R&D planned in 2009.Human embryonic stem (hES) cells lines carrying the mutant gene responsible for diseases may replicate associated molecular defects associated and be used, therefore, to analyse pathological mechanisms and search for treatments. I-STEM teams have shown that hES cell lines carrying the mutant gene responsible for myotonic dystrophy type1 (DM1) -the most frequent myopathy in adult- present known cellular and molecular abnormalities. hES capacity of self-renewal and pluripotency provides an unlimited and highly versatile cell resource, relevant for large-scale analyses. In order to exploit fully these potentials of hES cell lines within the framework of its exploration of therapeutics for monogenic diseases, I-STEM has set up a screening department through a close partnership with the companies Velocity11, Discngine and Prestwick Chemical. I-STEM has installed at its site, in Evry-Genopole, a powerful automation platform using the innovative Velocity11 BioCel1800(R) technology, coupled to a specific data management system designed by Discngine. The Conseil Régional d’Ile-de-France and the Association Française contre les Myopathies (thanks to the French Telethon donations) co-funded this platform[**]. The investments to build  this facility assays have been developed in order to screen the “FDA  approved” Prestwick Chemical library and a subset of the in house designed  siRNA (small interferent RNA) library.

Using this screening platform, the I-STEM teams have looked for compounds and siRNA that would provoke the disruption of abnormal aggregation seen in the nucleus of human embryonic stem cells carrying the DM1 mutation. Several of the 1120 compounds and 50 siRNA assayed were identified as candidates.

I–STEM intends to perform five to ten similar screening campaigns per year on other genetic diseases, using its library of human stem cell lines carrying genetic mutations[***].

About I-STEM

The Institute for Stem Cells in the Treatment and Study of Monogenic Diseases- is a laboratory which has set out to explore the therapeutic potential of stem cells in the treatment of rare genetic diseases. Headed by Marc Peschanski (an INSERM Research Director), I-STEM was in early 2005, the first lab in France to be allowed to work on (imported) human embryonic stem cell lines. Then, in June 2006, it was authorized by the French Agency for Biomedicine to set up a library of mutated cell lines that can serve as models in the study of monogenic diseases. For more information: http://www.istem.eu

The Symposium is focused on the new modality of multiple sclerosis treatment– immunosuppressive therapy followed by autologous stem cell transplantation. Centers in Europe, North and South America, Russia, China, Israel and Australia have successfully performed this procedure, and, to date, more than 600 stem cell transplantations in multiple sclerosis have been performed worldwide.

Along with promising results there are a number of unclear and challenging issues that are worth studying.

The Symposium intends to share the newly acquired knowledge in the field, to discuss the challenges and perspectives of the method, and to develop collaborative projects. The topics to be covered within the symposium include:

• Regimens of conditioning: Immunoablation or immunosupression?
• Types of transplantation: autologous or allogenic?
• Posttransplant immunological reconstitution
• Side effects
• Outcome measures: clinical, imaging, patient-reported outcomes
• Posttransplant neurorehabilitation
• Long-term follow-up results
• Proposal for cooperative studies

We invite the submission of abstracts on the above aspects of stem cell transplantation in multiple sclerosis. All abstracts will be reviewed by an international committee and a number of abstracts will be selected for oral presentation within the Symposium.

www.stemcellms.ru