Bio Screening Industry News

Archive for May, 2007

May 31, 2007

European research agenda for pathogenomics adopted

Filed under: Research Projects, Press Releases, Genomics, PathoGenomics — admin @ 4:50 pm

Network of Excellence EuroPathoGenomics has undergone its first review

Researchers have long been fascinated by microorganisms, as they can be both useful inhabitants of the body and dangerous pathogens. In 2005, to better understand this dual role, 37 researcher teams from 13 different European countries founded the Network of Excellence EuroPathoGenomics (NoE EPG). The members have now adopted a common Research Agenda for the field of pathogenomics, which lays out the core scientific challenges for the years to come and places emphasis on two aims in particular: In future, scientists intend to focus more on the interaction between the pathogens and the hosts, rather than exclusively analysing disease-causing microorganisms in isolation. Furthermore, the microbiologists’ aim is to strengthen cooperation with bioinformatic experts, in order to better manage the multitude of data that is produced in modern genomic research.

For decades, researchers have concentrated on the microorganisms that cause diseases. More recently however, thanks to the tools of modern genomics, they have been able to focus in detail on the molecular mechanisms behind the pathogens. To bundle European competencies in the field of pathogenomics and to strengthen the exchange of experiences, a total of 37 scientific laboratories from 13 different countries came together in 2005 under the umbrella of the European Network of Excellence EuroPathoGenomics NoE EPG. This initiative is being funded by the European Commission with 6.7 millions euros over five years. At the end of April, at a meeting in the Villa Vigoni in Italy, members undertook a first review of their cooperation. “Over the course of the previous years, we have focused mainly on establishing efficient infrastructures and making them available for all partners”, said Prof. Jörg Hacker from the University of Würzburg, who is coordinating the network. In particular, a central virtual cell strain collection has been completed, which allows for the rapid searching of suitable data. Furthermore, the “EuroPathoGenomics Graduate Academy” (EGA) has also been established, with more than 50 students participating in a number of training programmes.

In the future, NoE EPG-members intend to concentrate more on the strategic adjustment of their work with the aim of improving the coordination of research across the participating countries. In Italy, the network partners therefore adopted the first structure of a common European research agenda, which describes the most important challenges in pathogenomics that the scientists will be facing in the coming years. “In the long run, we have to focus more on analysing the interaction of the pathogens with the host as well as shedding light on the complex interplay between different microorganisms that are active at the same time”, said Hacker. Furthermore, in their daily work, the pathogenomics experts are confronted with the enormous quantity of data that results from genomic research. The scientists want to address this problem with the development of new bioinformatic approaches, which could particularly advance the comparison of different pathogenic genomes. “We have to use comparative genomics to discover both the molecular determinants that cause hospital infections and the factors that are responsible for the drug-resistance of pathogens”, said Mike Gilmore, Harvard Medical School, USA, at the meeting. Another goal of the agenda is better cooperation between basic scientists and clinicians. “Our scientific language is not well understood by clinicians. We should learn more from each other”, emphasised the German researcher Werner Goebel from the University of Würzburg,during the meeting in Italy.

More information: www.noe-epg.uni-wuerzburg.de

6th Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases November 14, 2007 - November 16, 2007

Filed under: USA and Canada — admin @ 4:27 pm

Focus Topic: RNAi and Therapeutic Targeting

Dates: November 14, 2007 - November 16, 2007

Location:

Sonoma Mission Inn and Spa
Sonoma, California

These annual interdisciplinary scientific symposia are designed to provide a novel and informal scientific setting for the dissmination and exchange of ideas and research findings by bringing together students, fellows, and junior/senior investigators who do not typically interact at other meetings. Our goal for these annual fall symposia is to provide the opportunity for interactions that are not possible at larger meetins. We hope to encourage synergy, facilitate new research directions and collaborations, and enhance current approaches to gene transfer/therapy for the treatment of human disease. Presentations focus on unpublished works-in-progress, cutting edge technologies, and key thematic issues.

www.gts.ucdavis.edu 

BioServe Names Kevin Krenitsky as Chief Executive Officer

Filed under: North America, Cancer Research, Press Releases, Genomics — admin @ 3:17 pm

Beltsville, MD, May 7, 2007 – BioServe today strengthened its senior management team with the appointment of Kevin Krenitsky, M.D. as Chief Executive Officer.  Krenitsky is a highly respected 15-year veteran of the life sciences industry, bringing a wealth of experience in building and managing global biotechnology operations.

“Kevin’s impressive range of experience in diagnostics, pre-clinical and clinical pharma, along with his in depth knowledge of our recently acquired Genomics Collaborative bio-banking business makes him the perfect fit to lead BioServe into the future,” said Rama Modali, Founder and President, BioServe. “Kevin’s operational experience along with his successful experience in launching new products and service offerings will be instrumental in growing BioServe’s global business. We are pleased that Kevin has joined BioServe and look forward to his contributions to the team.”

Prior to joining BioServe, Dr. Krenitsky was the Chief Executive Officer of Parkway Clinical Laboratories, a clinical diagnostic lab providing comprehensive routine and esoteric testing.  Prior to that he served as Senior Vice President and Division Head at SeraCare Life Sciences’ Genomics Collaborative Division (GCI) where he managed all worldwide pharmaceutical R&D collaborations.  Before GCI was acquired by Seracare Life Sciences, Dr. Krenitsky acted as the company’s Medical Director responsible for spearheading the development of GCI’s global network of five hundred-plus clinical sites on four continents. During his tenure at GCI, Dr. Krenitsky was instrumental in developing several hundred agreements with dozens of major pharmaceutical, biotechnology, and diagnostic companies worldwide. Dr Krenitsky received his M.D. from Jefferson Medical College.

Dr. Krenitsky commented, “I am extremely excited to join BioServe, a company that has forged a stellar reputation for genomic analysis among many of the world’s leading researchers. With the addition of the Genomics Collaborative bio-bank to the company’s comprehensive services, BioServe is on track to become the leader in helping researchers discover and validate a new generation of superior diagnostic and therapeutic targets.”

About BioServe

BioServe provides a comprehensive ‘biomaterial to validated data’ genomics services platform, helping researchers gain the pre-clinical data for breakthroughs in drug discovery, molecular diagnostics and pharmacogenomics. Utilizing BioServe’s genomics services platform, researchers can identify genetic markers, validate drug targets that cause disease and correlate clinical data with molecular data to accelerate the development of new and safer drugs. BioServe’s services extend from nucleic acids processing, DNA synthesis, high throughput sequencing and genotyping, genome wide-scans and gene expression analyses to ready-made large epidemiologically sound case-control studies of inflammatory disorders, endocrine disorders, cardiovascular disease, diabetes, hypertension, obesity and many cancers.  BioServe’s Global Repository® provides researchers with a library of 600,000 human DNA, tissue and serum samples linked to detailed clinical and demographic data from 140,000 consented and anonymized patients from four continents. BioServe’s customers include leading pharmaceutical and biotechnology companies, and government and academic research institutions. BioServe has headquarters in Beltsville, MD and Hyderabad, India. For more information please visit www.bioserve.com or call 301-470-3362.

Portrait™ 630 Reagent Multi-spotter Wins Technology Prize at MipTec 10th Anniversary Conference in Basel, Switzerland

Filed under: North America, Europe, Grants and Awards, Europe, Equipment, Press Releases — admin @ 3:14 pm

Sunnyvale, CA, May 22, 2007 - Portrait™ 630 Reagent Multi-spotter Wins Technology Prize at MipTec 10th Anniversary Conference in Basel, Switzerland

The European Laboratory Robotics Interest Group (ELRIG) has selected the Labcyte Portrait 630 reagent multi-spotter as the winner of its annual Technology Prize, awarded this year at the MipTec 10th Anniversary Conference, held May 8-11, 2007 in Basel, Switzerland. The award recognizes the most innovative product presented at the conference. A panel of independent judges selected the Portrait 630 system from among hundreds of products displayed by 114 vendors. The ELRIG is a not-for-profit organization, whose primary purpose is to provide a communication forum for members to increase their awareness of automation techniques and products used for scientific research, development or production. MipTec has evolved as the leading conference in Europe on enabling technologies in the drug discovery process. It combines a scientific program featuring scientific and technology experts with an accompanying exhibition.

The Portrait 630 reagent multi-spotter uses the Labcyte acoustic droplet ejection technology to bring automated reagent deposition to the new field of MALDI tissue imaging mass spectrometry (IMS). IMS links the label-free universal detection of mass spectrometry with the spatial information of molecular histology. IMS enables discovery in protein profiling, small molecule tracking, and other applications. The Portrait 630 reagent multi-spotter provides multi-step protocols, precise drop-on-drop positioning and flexible droplet timing, to automate sequential experiments such as proteolytic digests followed by matrix deposition. The Portrait 630 system enables users to optimize reaction conditions and crystal formation for more reproducible and higher quality mass spectra.

Labcyte Inc., headquartered in Sunnyvale, California, is the world leader in providing acoustic droplet ejection technology for pharmaceutical and life science applications. The award-winning Echo 500 series liquid handlers and Portrait 630 reagent multi-spotters are used in nine of the 10 largest pharmaceutical companies, as well as in leading academic and research institutions and contract research organizations worldwide. The Labcyte acoustic droplet ejection technology has broad applications including compound management, assays, arraying, particle manufacturing, imaging mass spectrometry, and live-cell transfer. Labcyte also provides a range of unique microplate consumables. Labcyte has 28 issued U.S. patents, 3 issued European patents and additional international filings. For more information, visit www.labcyte.com.

May 30, 2007

The imminent change of the antithrombotics market

Filed under: Business and Investment, Europe, Press Releases, Reports — admin @ 2:02 pm

The antithrombotics market with the two blockbusters enoxaparin and prasugrel is challenged by generic products as well as by next generation anticoagulants with oral administration and antithrombotics with an improved risk-benefit ratio

Barcelona, Spain | May 30, 2007 | The Business Intelligence firm La Merie S.L. reported today that the US$ 9.6 bln market of the two blockbuster antithrombotic agents enoxaparin and clopidogrel is going to be rearranged by loss of patent protection and emergence of phase III stage competitors with improved profiles. While Bristol-Myers Squibb already suffers from dropping sales (US$ 3.3 bln in 2006 for clopidogrel), Sanofi-Aventis will be affected stronger in its ex-US sales of clopidogrel (US$ 3 bln) and global sales of enoxaparin (3.3 bln). Sanofi-Aventis has the biggest anticoagulant pipeline by numbers, but does not lead the next generation of oral thrombin (factor IIa) and factor Xa inhibitors which have the potential to replace parenteral product enoxaparin, a low molecular weight heparin (LMWH). At least seven clinical stage direct thrombin inhibitors and at least 10 clinical stage direct factor Xa inhibitors are in the anticoagulant pipeline lead by Boehringer Ingelheim and Bayer Schering Pharma. Despite the larger market of the antiplatelet agent prasugrel, the number of advanced clinical stage antiplatelet projects is smaller than that of anticoagulants. These results and more were found in a competitor analysis conducted by La Merie Business Intelligence. The competitor analysis of Antithrombotics can be acquired at www.pipelinereview.com, La Merie’s News Center and Online Store.

The competitor analysis evaluated anticoagulant and antiplatelet agents in development. Apart from the oral direct factor IIa and Xa inhibitors, oral heparin and oral LMWH developments are ongoing and novel targets being explored in preclinical and clinical trials. Further companies with a strong antithrombotics portfolio include Daiichi-Sankyo, AstraZeneca and Organon & Schering-Plough. The convenience of oral administration will be the most obvious advante of the next generation anticoagulants, but the reduced incidence of thrombotic events and of bleeding side effects key to the commercial success under the light of the imminent approval of the first enoxaparin generics.

About La Merie
La Merie S.L. is a Business Intelligence enterprise fully dedicated to provide high quality R&D information to the biopharmaceutical industry. La Merie offers individual consultancy services and publishes reports and periodicals. For more information visit www.lamerie.com.
About PipelineReview.com
Pipelinereview.com is the News Center and Online Store of La Merie Business Intelligence focused on Research and Development in the Biopharmaceutical Industry. Visitors of PipelineReview.com will find R&D relevant press releases and can receive selected R&D news from one or more of the site’s News Channels. A free R&D Newletter conveniently brings via e-mail a daily selection of the most interesting news from biopharmaceutical R&D. For more information visit pipelinereview.com

May 23, 2007

WUSTL creates center to study women’s infectious diseases

Washington University School of Medicine in St. Louis is launching a new effort to study infectious diseases that preferentially affect women. The center for Women’s Infectious Disease Research (cWIDR) will focus on issues such as:

• microorganisms that cause urinary tract infections (UTIs) and other conditions that make urination and intercourse painful or difficult

• infections that lead to premature delivery and vaginitis

• potential contributing roles for microorganisms in life-threatening conditions such as cancer, heart disease, neurodegenerative disorders and diabetes.

“Infectious diseases of women is a tremendously underserved area,” says Scott Hultgren, Ph.D., the Helen L. Stoever Professor of Molecular Microbiology and the center’s director and principal investigator. “UTIs, for example, are one of the most common bacterial infections in women. They’re not fatal, but we need new and improved therapeutics because they’re a very significant cause of suffering, lost work days and health-care expenses.”

According to Hultgren, the center continues a University tradition of innovation and leadership in microbiology and infectious diseases. Stephen Beverley, Ph.D., Marvin A. Brennecke Professor and head of molecular microbiology, founded the center’s predecessor, the Center for Infectious Disease Research (CIDR) in 1997. He recently stepped down as director of CIDR and designated Hultgren as his successor.

Hultgren’s research has long been focused on women’s health and infectious diseases, with studies funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infectious Diseases. He has also been active in the Office of Research on Women’s Health, an agency that coordinates and advises on women’s health research throughout the National Institutes of Health.

Given those interests and experiences, Hultgren decided to reconceptualize CIDR and its goals, altering the center’s name to reflect the changes.

The center for Woman’s Infectious Disease Research is part of the University’s BioMed 21 initiative, which is focusing efforts at Washington University on speedy translation of laboratory discoveries into new approaches for diagnosis and treatment of patients.

According to Larry J. Shapiro, M.D., executive vice chancellor for medical affairs and dean at the School of Medicine, studying gender-specific infections can reveal information that is helpful in a much broader range of diseases.

“Scott’s work with urinary tract infections has led to insight into how the bacteria that cause these infections sometimes defend themselves by cooperating to form a protective shield known as a biofilm,” he says. “Many common infections of both men and women employ this defense against antibiotics and the host immune system, and to improve treatment for these infections we have to devise medicines that can penetrate this shield.”

Other major infectious disease issues specific to women include interstitial cystitis or painful bladder syndrome, a condition estimated to afflict hundreds of thousands of females per year. Symptoms are similar to urinary tract infections and include frequent, painful urination and pain during intercourse. Diagnosis and treatment are difficult because scientists don’t yet know the cause of the condition.

Oral and vaginal infections with streptococcus and other bacteria have been linked to premature delivery in pregnant women. Michael Caparon, Ph.D., professor of molecular microbiology and co-director of the center for Woman’s Infectious Disease Research, plans to bring microbiologists and obstetricians to learn why and determine what can be done.

Fostering collaboration between different disciplines to create new perspectives on the big challenges of biomedicine is a primary goal of BioMed 21. Hultgren plans to establish many connections and collaborations between his center and other research centers, noting the potential for synergy provided by the Center of Genome Sciences and other research groups at the University.

“We see the center for Woman’s Infectious Disease Research as part of a multi-disciplinary network combining a powerful blend of microbial pathogenesis, genomics, structural biology, biochemistry and biophysics, and diverse imaging technologies,” Hultgren says.

As an example, Hultgren’s work with urinary tract infections led to detailed study of pili, fibers produced by the bacteria that cause the infections. Pili allow bacteria to adhere to and invade human tissues, and Hultgren’s laboratory has recently found that they help hold bacteria together in biofilms. These discoveries made it possible to design molecules that block pili formation and may one day lead to improved treatments.

Bacteria also manufacture fibers comprised of substances known as amyloids. Like pili, these materials contribute to biofilm formation and host cell colonization, but they’re much more well-known for the role they play in neurodegenerative disorders and other diseases. Hultgren hopes to recruit experts who can use bacteria to model amyloid formation and design compounds that block their assembly.

“Amyloid plaques in the brain are a primary characteristic of Alzheimer’s disease, a terrible disease affecting women and men, so we plan to offer the inhibitors we develop to neurologists as potential treatments for that disorder,” Hultgren says.

Researchers at the center for Woman’s Infectious Disease Research also will study whether microorganisms are playing a role in serious diseases not previously thought to be related to infection. As evidence of why a search for such connections might prove fruitful, Hultgren highlights the surprising discoveries that infectious agents are responsible for all stomach ulcers and most cervical cancers.

In a newer, more tentative link likely to be further probed at the center for Woman’s Infectious Disease Research, scientists have found that a receptor in the circulatory system responds to both fat deposits and bacterial infections. The receptor is believed to help summon an immune response when it detects the bacteria, and cardiologists speculate that its responsiveness to fat may mean the receptor is also triggering inflammatory responses that contribute to heart disease. If so, blocking the receptors could offer a new path to prevention.

To accelerate the search for new treatments for infectious diseases, Hultgren has established close ties with a local biotech firm, Sequoia Sciences, and with Tom Ellenberger, Ph.D., the Raymond H. Wittcoff Professor and head of Biochemistry and Molecular Biophysics.

“Tom has started a program for high-throughput screening of small molecules with pharmaceutical potential, and Sequoia has a library of approximately 250,000 antibacterial compounds isolated from plants in collaboration with the Missouri Botanical Garden,” Hultgren explains. “As we develop assays that help us know what we’re looking for in a treatment, we’ll be using those two resources to rapidly seek out compounds that meet our criteria.”

The new center and five new faculty positions will be supported in part by funding from the school’s Departments of Medicine, Molecular Microbiology, Infectious Diseases and Cardiology as well as general medical school resources and donors.

“If we can get a synergistic effect going on in terms of the interactions between these and other disciplines, then I really feel we’re going to be able to make a significant difference in women’s health,” Hultgren says.

Amylin invests $10M in BioSeek

BioSeek, based in Burlingame, will work with San Diego-based Amylin (NASDAQ: AMLN) on treatments for inflammatory diseases. The work will put Amylin’s proprietary drug compounds through BioSeek’s biological screening systems to seek useful drugs. BioSeek can choose two peptide compounds after screening and develop them if it wishes, paying milestones and royalties to Amylin if it does.

The two companies signed an earlier collaboration last year.

Peter Staple, BioSeek’s CEO, praised the deal as a source of money for his company, as well as a way to gain access to important compounds and research in inflammatory diseases.

May 18, 2007

Talent Management in Research & Clinical Development June 28th & 29th, 2007

Filed under: Europe — admin @ 7:05 pm

LOCATION
Hotel Marriott - Vienna, Austria

ORGANIZER:
Next Level Pharma.
Bratislava, Slovak Republic
URL: www.nextlevelpharma.com
Phone: +421 232 662 621
Fax:     +421 232 662 622

This conference is focusing on the constant challenge of identifying, attracting, motivating and retaining talent in research and clinical development in order to accelerate R&D in a globalised market.

With fewer scientific and medical graduates annually in Europe & the USA and increasing global labour mobility, life sciences R&D is under increasing pressure to recruit, engage and develop the best R&D talent available and minimize turnover rates.

This meeting focuses on how pharma and biotechs can leverage their career development and training programs, exciting R&D projects, corporate branding, and compensation & benefits programs to enhance recruitment and retention rates in R&D and therefore increase R&D productivity.
Key topics:

Learn how to recognise and develop the more “technically focused” talent and how to motivate and engage scientists and medical professionals in rewarding and exciting, long-term careers.

Learn how to proactively build your R&D talent pipeline by evaluating and optimising your sourcing strategies.

Benchmark your compensation & benefits programs to maximize your global talent attraction and retention in R&D.

Learn where the future geographical talent pools are emerging for R&D and how to gain access to them.

Discover how biotechs can compete with big pharma, diagnostics and medical device companies for the suitable R&D Talent

May 16, 2007

Related Fragment Screening: Swift and Easy Elucidation of Drug Metabolites

Filed under: North America, ChemInformatics, New Products, Press Releases — admin @ 8:14 pm

Software assigns, interprets and organizes LC/MS data, making it easier to visualize structural relationships between parent drugs and metabolites. Related fragment screening will be highlighted at an ACD/Labs MS Seminar (register) held in advance of the 55th ASMS Conference on Mass Spectrometry on Sunday, June 3rd, from 1:30-4:30 p.m. in Indianapolis, IN.

Toronto, Canada (PRWEB) May 4, 2007 — Researchers in the field of drug metabolism take note of a new method for quickly and easily identifying and elucidating the structures of related compounds by LC/MS with related fragment screening and ACD/IntelliXtract.

Related fragment screening takes advantage of the fact that related compounds, such as drug metabolites or degradants, will have some chemical structure similarities to the parent drug. The mass spectra will therefore be similar, as common substructures will yield common fragment ions. Mass spectral relationships can then be used to identify potential metabolites. Furthermore, the relationship between chemical structure and mass spectrum may be used to elucidate the structure of potential metabolites by identifying the sites of modification on the parent drug. Conceptually, this seems simple; however, in practice, interpreting complex LC/MS data can be very challenging.

Software can interpret, label and organize mass spectral data, making it easier to extract common and related fragment information. Mass spectrum interpretation tools help chemists visualize the relationships between the parent drug and related compounds. ACD/IntelliXtract has the capability to extract chromatographic components, and interpret the pure-component spectrum for each, automatically assigning MH+ or MH- adducts, multimers and fragment ions. This helps mass spectrometrists quickly glean the relevant information from LC/MS data sets, easing the burden of spectrum interpretation, so that analysts spend less time on routine identification and confirmation, and can focus on solving more challenging problems.

An illustration of how to use ACD/IntelliXtract for related fragment screening in an example of forced degradation was recently presented in a talk at Pittcon 2007 entitled ‘Identification of Impurities Using Liquid Chromatography Hyphenated with Tandem Mass Spectrometry’.

“IntelliXtract can now combine mass spectral identifiers such as 12C, 13C, and MH+, with knowledge of the parent structure, the differences in mass between parent and some unknown, and the inherent shifts in the fragments of these related compounds,” commented Mark Bayliss, Director of Analytical Informatics, ACD/Labs. “This is an important step towards automated structure building from mass spectra. The future is certainly looking to be very exciting in this field.”

More information about related fragment screening can be obtained by downloading the application note Extraction and Elucidation of Metabolites using Related Fragment Screening from the ACD/Labs website. The note illustrates the use of related fragment screening using ACD/IntelliXtract to help identify and determine the structure of metabolites of the antiarrhythmic drug verapamil.

Related fragment screening will be highlighted at an ACD/Labs MS Seminar (register) held in advance of the 55th ASMS Conference on Mass Spectrometry on Sunday, June 3rd, from 1:30-4:30 p.m. in Indianapolis, IN. View the seminar agenda.

For more information on ACD/IntelliXtract and ACD/MS Manager visit our website www.acdlabs.com

About Advanced Chemistry Development, Inc.
Advanced Chemistry Development, Inc., (ACD/Labs) is a chemistry software company offering solutions that truly integrate chemical structures with analytical chemistry information to produce ChemAnalytics®. ACD/Labs creates innovative software packages that aid chemical research scientists worldwide with spectroscopic validation of structures, elucidation of unknown substances, chromatographic separation, medicinal chemistry, preformulation of novel drug agents, systematic nomenclature generation, and chemical patenting and publication. Combined, ACD/Labs’ solutions create an analytical informatics system that provides dramatic feed-forward effects on the chemical and pharmaceutical research process. Founded in 1994, and headquartered in Toronto, Canada, ACD/Labs employs a team of over 145 dedicated individuals whose continual efforts carry ACD/Labs’ innovative technologies into pharmaceutical, biotech, chemical, and materials companies throughout the world. Information about Advanced Chemistry Development and its products is available at www.acdlabs.com.

New compounds promising candidates for neurodegenerative disease drug development

Scientists have developed a novel strategy for tackling neurodegenerative diseases such as Huntington’s disease: encouraging an individual’s own cells to “eat” the malformed proteins that lead to the disease.

Huntington’s disease is one of a number of degenerative diseases marked by clumps of malformed protein in brain cells. Symptoms include abnormal movements, psychiatric disturbances like depression and a form of dementia. The gene responsible for the disease was discovered in 1993, leading to a better understanding of the condition and to improved predictive genetic testing, but it has yet to lead to any treatments that slow the neurodegeneration in Huntington’s patients.

Professor David Rubinsztein, a Wellcome Trust Senior Clinical Fellow at the University of Cambridge, has been studying the molecular biology underlying Huntington’s and other neurodegenerative diseases. Huntington’s occurs when a protein known as huntingtin builds up in the brain cells of patients, mainly in neurons in the basal ganglia and in the cerebral cortex. Normally, cells dispose of or recycle their waste material, including unwanted or mis-folded proteins, through a process known as autophagy, or “self-eating”.

“We have shown that stimulating autophagy in the cells , in other words, encouraging the cells to eat the malformed huntingtin proteins , can be an effective way of preventing them from building up,” says Professor Rubinsztein. “This appears to stall the onset of Huntington’s-like symptoms in fruit fly and mice, and we hope it will do the same in humans.”

Autophagy can be induced in mouse and fly models by administering the drug rapamycin, an antibiotic used as an immunosuppressant for transplant patients. However, administered over the long term, the drug has some side effects and Rubinsztein and colleagues are aiming to find safer ways of inducing autophagy long term.

Now, Professor Rubinsztein, together with Professor Stuart Schreiber’s lab at the Broad Institute of Harvard/MIT, Boston in the US, and Dr Cahir O’Kane’s group in the Department of Genetics at the University of Cambridge have found a way of identifying novel “small molecules” capable of inducing autophagy. The research is published today in the journal Nature Chemical Biology.

The screening process involves identifying small molecules that enhance or suppress the ability of rapamycin to slow the growth of yeast, though the selected molecules have no effects on yeast growth by themselves. Yeast is a single-celled organism and therefore less complex to study for initial screening purposes.

Three of the molecules that enhanced the growth-suppressing effects of rapamycin in yeast were also found to induce autophagy by themselves in mammalian cells independent of the action of rapamycin. These molecules enhanced the ability of the cells to dispose of mutant huntingtin in cell and fruit fly models and protect against its toxic effects.

“These compounds appear to be promising candidates for drug development,” says Professor Rubinsztein. “However, even if one of the candidates does prove to be successful, it will be a number of years off becoming available as a treatment. In order for such drugs to be useful candidates in humans, we will need to be able to get them into right places in the right concentrations, and with minimal toxicity. These are some of the issues we need to look at now.”

http://www.wellcome.ac.uk
Source: Medical Research News

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