Yellow Fever In Togo

The mass vaccination campaign is scheduled to begin today in Savanes and Kara regions where three cases of yellow fever were laboratory confirmed. Yellow fever reappeared in these regions after an absence of more than 20 years.

The campaign will target children more than 9 months old in 11 districts in these 2 regions. The vaccine (1 500 000 doses) has been provided by the The GAVI Alliance emergency stockpile, through the International Coordinating Group (ICG) on Vaccine Provision for Yellow Fever Control. ECHO has provided funding for the campaign.

An additional two cases of yellow fever were reported at the end of January, one in Kara region(Kozah district) and the other in Maritime region (Lacs district); both cases were laboratory confirmed by Institut Pasteur, Dakar, Senegal.

An investigation was carried out by the Ministry of Health, assisted by the WHO Regional Office for Africa and the WHO country office. Containment measures, including a vaccination campaign in Maritime region are currently being assessed.

For more information
– Yellow fever
Department of Epidemic and Pandemic Alert and Response

http://www.who.int

Metabasis Announces Completion Of Enrollment In The Phase 2b Clinical Trial For CS-917 In Patients With Type 2 Diabetes

Metabasis Therapeutics (Nasdaq: MBRX) today announced that enrollment was recently completed in the ongoing Phase 2b clinical trial for CS-917, a compound being developed for the treatment of type 2 diabetes by Daiichi Sankyo pursuant to a licensing agreement between the two companies. This proof-of-concept study is designed to evaluate safety and tolerability after three months of dosing of CS-917, as well as its effect on blood levels of the molecule HbA1c, an important measure of glucose control in patients with type 2 diabetes.

A total of 392 patients have been enrolled at over 100 sites in this randomized, double-blind, placebo controlled trial. Patients are evenly distributed among four groups consisting of two active dose groups of CS-917, an active comparator and placebo. If successful, the trial could support selection of a dose for a pivotal Phase 3 clinical trial.

In two successfully completed Phase 2a clinical trials (14-day and 28-day) in patients with type 2 diabetes, CS-917 was well tolerated and significantly reduced the elevated blood glucose levels that characterize the disease. The results from the 14-day Phase 2a clinical trial involving 39 patients were presented at the 2006 American Diabetes Association meeting and showed that oral administration of CS-917 in the morning resulted in significant lowering of post-dose fasting plasma glucose (FPG) compared to placebo. This study was followed by a 28-day study in 146 type 2 diabetic patients which indicated that CS-917 was most likely to be administered twice daily.

“The completion of patient enrollment in this trial is another step forward in the development of this novel compound, designed to inhibit gluconeogenesis, for patients suffering from type 2 diabetes,” stated Dr. Paul Laikind, president and chief executive officer of Metabasis. “With an estimated 180 million people worldwide with type 2 diabetes and with the incidence continuing to grow, new treatment options are urgently needed as current therapies often only achieve modest reduction in the production of glucose. We believe that CS-917 is the first of a new therapeutic class that has the potential to be an important distinctive approach for treating patients who suffer from type 2 diabetes.”

Dr. Mark Erion, executive vice president of research and development and chief scientific officer at Metabasis, commented. “CS-917 acts as a direct inhibitor of the pathway in the liver responsible for the production of glucose, the gluconeogenesis pathway. CS-917 is being evaluated to determine whether it may be used alone or in combination with certain other drugs designed to enhance removal of glucose from the bloodstream, and for the large number of patients who are unable to take metformin, a treatment currently used as first line therapy in patients with type 2 diabetes.”

About CS-917:

CS-917 is a compound for the treatment of type 2 diabetes that was discovered by using Metabasis’ proprietary NuMimetic(TM) technology, and is being developed by Daiichi Sankyo pursuant to a licensing agreement between Metabasis and Daiichi Sankyo. Metabasis retains co-promotion rights in North America. CS-917 is a prodrug of an orally active, potent and selective inhibitor of fructose-1, 6-bisphosphatase (FBPase), a regulatory enzyme in the pathway responsible for the production of glucose in the liver, known as the gluconeogenesis pathway. By specifically inhibiting this pathway, liver glucose production should be reduced and blood sugar levels decreased in patients with diabetes, independent of insulin levels, body weight and disease stage. Metabasis believes that CS-917 is the first product candidate to be studied in human clinical trials that is designed to directly block this pathway.

Forward-Looking Statements:

Statements in this press release that are not strictly historical in nature constitute “forward-looking statements.” Such statements include, but are not limited to, references to the potential success of the Phase 2b clinical trial for CS-917 as well as the potential use and efficacy of CS-917. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause Metabasis’ actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, the progress and timing of clinical trials for Metabasis’ product candidates; the fact that positive results from clinical trials does not necessarily mean later clinical trials will succeed; difficulties or delays in development, testing, obtaining regulatory approval, producing and marketing Metabasis’ product candidates; the potential and progress of preclinical compounds and programs; and risks and uncertainties discussed in the “Risk Factors” section of Metabasis’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2006 and in Metabasis’ other filings with the Securities and Exchange Commission. All forward-looking statements are qualified in their entirety by this cautionary statement. Metabasis is providing this information as of this date of this release and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

About Metabasis

Metabasis Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs to address some of the world’s most widespread and costly chronic diseases. The Company has established a pipeline that includes clinical stage and preclinical product candidates targeting major diseases with significant unmet medical needs. Targeted diseases include major metabolic diseases such as diabetes, hyperlipidemia and obesity as well as liver diseases such as hepatitis and primary liver cancer. Metabasis has developed several proprietary technologies for use in discovering and optimizing drugs, including the NuMimetic(TM) and HepDirect(R) technologies. Metabasis is continuing to identify and develop new product candidates using its proprietary technologies and expertise.

Metabasis Therapeutics, Inc.
http://www.mbasis.com

Potential New Therapeutic Target For Asthma, Allergies And Cancer

Virginia Commonwealth University researchers have identified how a bioactive molecule involved with allergy, inflammation and cancer is transported out of mast cells, according to findings published online this week in the Proceedings of the National Academy of Sciences.

Mast cells are specialized cells that react to allergy-causing agents by releasing substances that trigger the body’s allergic response, leading to conditions like asthma and hives. Among the molecules released by mast cells that participate in the allergic response is sphingosine-1-phosphate. This molecule is also implicated in cancer.

The work by the VCU investigators opens up a new approach to treating asthma, which affects about 15 million Americans and is increasing in incidence and mortality, especially among African-Americans. It also has implications for other allergic disorders and for cancer in terms of developing drugs that inhibit the transport of SIP out of cells.

Sarah Spiegel, Ph.D., professor and chair, VCU Department of Biochemistry, and colleagues reported how S1P, which also regulates many important physiological functions in cells, is transported out of mast cells. S1P is produced by all cells and secreted by some cells into the circulation where it can bind to specific S1P receptors. Until now, researchers have not known the mechanism by which S1P is transported out of cells.

“Our study shows that mast cells can use a special kind of transporter that has long been known to be used by cancer cells to push anti-cancer drugs out and help them survive the treatment,” said Spiegel. “Our study is the first to establish a mechanism by which S1P can be exported out of mast cells and perhaps by cancer cells as well.”

In previous research, Spiegel’s team found that S1P levels are significantly elevated in fluid collected from the lungs of asthmatic patients after exposure to an allergen. Those findings led Spiegel’s team to believe that mast cells could be a source of S1P. Mast cells are found in all body tissues and rapidly produce and secrete a number of inflammatory substances such as histamine and S1P when activated by an inflammatory stimulus. Spiegel said that S1P in turn amplifies allergic and inflammatory responses. Therefore, S1P secreted from mast cells can orchestrate many allergic responses, including asthma.

This work was supported by a grant from the National Institutes of Health.
The team included researchers Poulami Mitra, a Ph.D. candidate, Carole A. Oskeritzian, Ph.D., Shawn G. Payne, Ph.D., from the VCU Department of Biochemistry; Michael A. Beaven, Ph.D., a researcher with the National Heart, Lung, and Blood Institute; and Sheldon Milstien, Ph.D., a neuroscientist with the National Institute of Mental Health.

About VCU and the VCU Medical Center:
Located on two downtown campuses in Richmond, Va., Virginia Commonwealth University ranks among the top 100 universities in the country in sponsored research and enrolls 30,000 students in more than 180 certificate, undergraduate, graduate, professional and doctoral programs in the arts, sciences and humanities in 15 schools and one college. Sixty of the university’s programs are unique in Virginia, and 20 graduate and professional programs have been ranked by U.S. News & World Report as among the best of their kind. MCV Hospitals, clinics and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the leading academic medical centers in the country. For more, see http://www.vcu.edu/.

Contact: Sathya Achia-Abraham
Virginia Commonwealth University

Medical Marijuana Might Reduce Nerve Pain Among People Living With HIV/AIDS, Study Says

Medical marijuana might reduce the pain of peripheral neuropathy, a type of nerve damage, among people living with HIV/AIDS, according to a study published in the Feb. 13 issue of the journal Neurology, the Washington Post reports (Weiss, Washington Post, 2/13). Donald Abrams of the University of California-San Francisco and colleagues examined the effects of smoking medicinal marijuana among people living with HIV/AIDS during a two-year period beginning in May 2003, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 2/13). Researchers enrolled 50 HIV-positive participants who reported severe foot pain caused either by HIV/AIDS or their medications, according to the Post (Washington Post, 2/13). The participants each spent a week at a secure laboratory at San Francisco General Hospital and were required to stop marijuana use before the start of the study (San Francisco Chronicle, 2/13). The researchers measured baseline pain among the participants by asking them to rank their pain on a scale of one to 100 and by administering two standardized tests involving a small hot iron applied to the skin and hot chili pepper cream (Washington Post, 2/13). Twenty-five participants were randomly chosen to receive active marijuana cigarettes with 3.5% THC, the drug’s active ingredient, and 25 received a placebo (San Francisco Chronicle, 2/13). The participants smoked three times daily — at 8 a.m., 2 p.m. and 8 p.m. — for five days (Washington Post, 2/13). The study found that after the first cigarette on the first day, at least 50% of participants who received active marijuana reported a 72% reduction in pain (San Francisco Chronicle, 2/13). The researchers recorded a 15% reduction in pain among those who received the placebo cigarette (Vesely, Oakland Tribune, 2/12). Over five days, the median reduction in pain reported by the active marijuana smokers was 34%, compared with 17% in the placebo group, the study found (San Francisco Chronicle, 2/13). The researchers took steps to ensure that the marijuana in the study — which was grown on the government’s official marijuana farm in Mississippi and stored in a locked freezer — was not used for recreational purposes, according to the Post (Washington Post, 2/13).

Comments, Reaction
The results are “evidence, using the gold standard for clinical research, that cannabis has some medical benefits for a condition that can be severely debilitating,” Abrams said (San Francisco Chronicle, 2/13). He added, “I think that there are people out there who say there is no evidence that marijuana is medicine, that this is all just a smoke screen.” David Murray, chief scientist for the White House Office of National Drug Control Policy, said the physical pain of people living with HIV/AIDS is an issue of great concern. However, “this particular study is not terribly convincing” because of methodological problems, Murray said (Dunham, Reuters, 2/12). He added, “People who smoke marijuana are subject to bacterial infections in the lungs. Is this really what a physician who is treating someone with a compromised immune system wants to prescribe?” (Elias, AP/Casper Star-Tribune, 2/13). Barbara Roberts — former interim associate deputy director in the Office of National Drug Control Policy and now with Americans for Safe Access — said, “This should be a wake-up call for Congress to hold hearings to investigate the therapeutic use of cannabis and to encourage more research” (Washington Post, 2/13). Igor Grant — director of the University of California Center for Medicinal Cannabis Research, which funded the study — said that although the study’s finding are “very promising,” they are not definitive (San Francisco Chronicle, 2/13).

The study is available online.

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Chromium Picolinate Shows Greater Clinical Benefits In Diabetes Management Than Other Forms Of Chromium Supplements

Nutrition 21, Inc. (Nasdaq: NXXI) reported today that a peer-reviewed analysis on chromium picolinate was published in the current edition of Diabetes Technology & Therapeutics. The analysis confirms that chromium picolinate is effective in improving glycemic control and normalizing lipid levels in people with type 2 diabetes. (1) The review, which analyzed research on chromium picolinate, supports the consistent beneficial effects of chromium picolinate and refutes a previous review that analyzed efficacy after combining results from all types of supplemental chromium. (2)

“The main messages are that all forms of chromium are not equivalent, and that higher doses of chromium picolinate are required for people with type 2 diabetes,” said C. Leigh Broadhurst, PhD, Research Chemist, the lead author of the publication. “Previous chromium reviews examined all types of chromium at widely varying doses. But separating out chromium picolinate, which yields highly consistent results in research studies, compared to other chromium supplements shows that at doses between 200-1000 mcg it is a superior nutritional adjunct to diabetes treatments.”

The review analyzed 15 clinical studies of people with diabetes. All studies showed chromium picolinate produced benefits in one or more standard measures of diabetes management, with no adverse events reported. The studies examined people with type 2, type 1, gestational and corticosteroid-induced diabetes. Although glycemic control varied by trial, all 15 trials showed improvements in one or more measurements of glycemic control, including fasting glucose, postprandial glucose, fasting insulin, postprandial insulin, glycated hemoglobin, or insulin sensitivity. The authors concluded the greater bioavailability of chromium picolinate compared to other forms of chromium may explain its comparatively significant superior effects on glycemic and lipidemic control. Supplemental chromium is available in several forms, including chromium picolinate, chromium chloride, and chromium nicotinate. (3) Research indicates that chromium picolinate, the most studied form of chromium, has enhanced absorption and efficacy. A human clinical study conducted by Ohio State University Department of Nutrition and presented at the 2005 Federation of American Societies for Experimental Biology (FASEB) annual meeting showed that chromium picolinate is better absorbed than other commercially available forms of chromium. (4) Additionally, an animal study conducted at the U.S. Department of Agriculture and published in the Journal of the American College of Nutrition found that chromium picolinate was better absorbed by the tissues (e.g., liver and muscle) than chromium nicotinate and chromium chloride. (5) Absorption into the tissue is important because for a mineral to be beneficial, it must survive the digestive tract and reach the bloodstream. Otherwise, minerals pass through the body, leaving it void of necessary nutrients. (6)

About the Scientific Review

The studies reviewed in this paper were identified from a number of sources, such as PubMed, Science Direct, and a past review of chromium effects on glycemic control. A total of 1,690 subjects, including 1,505 receiving chromium picolinate, participated in these trials. Twelve of the 15 studies were randomized, controlled trials and three were open-label trials. Chromium picolinate dosages ranged from 200-1000 mcg chromium per day, and the duration of the supplementation ranged from one week to 10 months.

Chromium Picolinate for Diabetes

Chromium picolinate, which is sold in combination with the B-vitamin biotin under the brand name of Diachrome(R) for people with diabetes, is an essential trace mineral that helps to regulate insulin function. The chromium picolinate in Diachrome has been recognized as safe by many of the world’s leading government and academic research institutions, including the U.S. Food and Drug Administration, the Institute of Medicine and the UK’s Food Standards Agency. In addition, biotin has been deemed safe by the U.S. Food and Drug Administration and is also Generally Recognized as Safe (GRAS) for use in foods and supplements.

About Nutrition 21

Nutrition 21 is a nutritional bioscience company and the maker of chromium picolinate-based, selenium and omega-3 fish oil-based supplements with health benefits substantiated by clinical research. Nutrition 21 holds 33 patents for nutrition products and uses. The company markets Chromax(R) chromium picolinate, which is the most-studied form of the essential mineral chromium. Chromax, a supplement for healthy and pre-diabetic people that promotes insulin health and helps improve blood sugar metabolism, cardiovascular disease, control cravings and fight weight gain, is now available through food, drug and mass retailers nationwide. Another chromium picolinate-based supplement developed and marketed by Nutrition 21 is Diachrome(R), a proprietary, non-prescription, insulin sensitizer for people with type 2 diabetes. It is sold in select drug retailers nationwide. Nutrition 21 also markets Selenomax(R), a high selenium yeast supplement that stimulates and protects the immune system by supporting antibody production and preventing free-radical damage. Selenomax is available at CVS/pharmacy in all its 6,200 retail stores across the country, including PharmaCare Specialty Pharmacy locations, and on http://www.cvs.com. The Company is the exclusive importer of Icelandic fish oils, including omega-3 fatty acids, which are manufactured to pharmaceutical standards and sold under the Iceland Health(R) brand. More information is available at http://www.nutrition21.com/.

(1) Broadhurst. CL, Domenico P Clinical Studies on Chromium Picolinate Supplementation in Diabetes Mellitus – A Review. Diabetes Technol Ther. 2006 Dec; 8(6):677-87

(2) Althuis MD, Jordan NE, Ludington EA, Wittes JT. Glucose and insulin responses to dietary chromium supplements: a meta-analysis. Am J Clin Nutr. 2002 Jul;76(1):148-55

(3) Dietary Supplements Fact Sheet: Chromium. Accessed November 2, 2005 from http://dietary-supplements.info.nih.gov/factsheets/chromium.asp.

(4) DiSilvestro, R, et al. Acute Absorption of Various Types of Chromium Supplement Complexes. Accepted for presentation at the Federation of American Societies for Experimental Biology (FASEB) annual meeting, San Diego, CA, April 4, 2005.

(5) Anderson, RA, et al. Lack of Toxicity of Chromium Chloride and chromium Picolinate in Rats. J Amer Coll Nut Vol. 16, No. 3 1997; 273- 279.

(6) Q&A. Accessed October 26, 2005 from http://www.traceminerals.com/questions.html.

Nutrition 21
http://www.nutrition21.com

Emergency Department Visits Necessary For Large Number Of Adverse Drug Events

Each year, an estimated 700,000 persons experience adverse drug events that lead to emergency department visits, according to a study in the October 18 issue of JAMA.

Outpatient use of drug therapies in the United States is common. In 2004, 82 percent of the U.S. population reported using at least 1 prescription medication, over-the-counter medication, or dietary supplement in the previous week and 30 percent reported using 5 or more of these drugs, according to background information in the article. While these medications may offer substantial benefits, there also may be risks. Information on outpatient adverse drug events (ADEs) has been difficult to collect, but the problem is large and can be expected to increase.

Daniel S. Budnitz, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues analyzed data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (NEISS-CADES) to determine the frequency and characteristics of ADEs in the U.S. that have led to emergency department visits. The study included data from Jan. 2004 through Dec. 2005.

Over the 2-year study period, 21,298 adverse drug event cases were reported. “Based on data from a nationally representative surveillance system, we estimate that more than 700,000 patients were treated for ADEs in U.S. emergency departments annually in 2004 and 2005, and 1 of every 6 required subsequent hospital admission, transfer to another health care facility, or emergency department observation admission. Individuals aged 65 years or older were more than twice as likely to be treated in emergency departments for an ADE and nearly 7 times as likely to require hospitalization as individuals younger than 65 years. Among all patients who were hospitalized, most ADEs were due to unintentional overdoses and two-thirds of these were due to toxicity from a relatively small set of drugs for which regular monitoring is commonly required to prevent acute toxicity. Sixteen of the 18 drugs most commonly causing ADEs have been in clinical use for more than 20 years,” the authors write.

Adverse drug events accounted for 2.5 percent of estimated emergency department visits for all unintentional injuries and 6.7 percent of those leading to hospitalization, and also accounted for 0.6 percent of estimated emergency department visits for all causes.

Insulins or warfarin, drugs that typically require ongoing monitoring to prevent overdose or toxicity, were implicated in 1 in every 7 estimated ADEs treated in emergency departments.

“The finding that individuals aged 65 years or older (12 percent of the U.S. population) accounted for one-quarter of ADEs overall and half of adverse events requiring hospitalization highlights the importance of directing ADE prevention efforts to this vulnerable population. Emergency department visits for ADEs in this age group were nearly as common as those for motor vehicle occupant injuries,” the authors write.

“Efforts to reduce the burden of outpatient ADEs have been hampered by sparse data, except in selected health care systems or settings. Ongoing data collection in NEISS-CADES will enable more detailed examination of the epidemiology of emergency department-treated outpatient ADEs, focusing on specific patient populations, drug classes, conditions, and circumstances. Identifying appropriate measures of drug exposure and evaluating drug risks in relation to drug benefits remain important challenges in improving the quality of outpatient drug therapy,” the researchers write.

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(JAMA. 2006;296:1858-1866.)

Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Contact: Jennifer Morcone
JAMA and Archives Journals

Brazil To Distribute 10M Condoms Ahead Of Carnival As Part Of HIV Prevention Campaign

The Brazilian Ministry of Health plans to distribute 10 million condoms at no cost ahead of the 2007 Carnival festivities as part of its effort to prevent the spread of HIV and other sexually transmitted infections, ministry officials said on Sunday, the AP/International Herald Tribune reports. According to a 2005 survey released by the health ministry earlier this month, almost one-third of young Brazilians responded that they did not use a condom the last time they had sex because one was not available or they could not afford one. Health Minister Agenor Alvares at a news conference in Rio de Janeiro said, “The idea of this campaign is to show that the joy that comes with Carnival must be accompanied by some precautionary measures.” The HIV prevention campaign also will include several nationally broadcast radio and TV advertisements, the official Agencia Brasil news service said. About 15 million condoms have been distributed this year, according to the health ministry. Cardinal Geraldo Majella, president of Brazil’s Roman Catholic Bishops Conference, said that he does not believe condom distribution efforts will help curb the spread of HIV in the country. This year’s Carnival festivities are scheduled to take place from Feb. 17 to Feb. 20 (Azzoni, AP/International Herald Tribune, 2/11).

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

Simple Classification Can Help Define And Predict Limb-Threatening Diabetic Infections

Research groups from Texas, Chicago, Washington State and the Netherlands partnered to publish a landmark study validating the Infectious Disease Society of America’s guidelines for the clinical classification of diabetic foot infections.

“We’re all very pleased to see this study in print,” noted co-author David G. Armstrong, DPM, PhD, Professor of Surgery at Scholl’s Center for Lower Extremity Ambulatory Research (CLEAR) at Rosalind Franklin University. “What this provides us now is confirmation that a simple system that labels infections as mild, moderate or severe can have a dramatic impact on predicting hospitalization and amputation. This will go a long way toward helping us to most effectively guide therapy and communicate with our patients.”

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The study is published in the February issue of the journal Clinical Infectious Diseases. The classification system itself is freely available at http://www.diabetic-foot.net/.

Rosalind Franklin University of Medicine and Science educates medical doctors, health professionals and biomedical scientists in a personalized atmosphere. The University is located at 3333 Green Bay Road, North Chicago, IL 60064, and encompasses Chicago Medical School, College of Health Professions, Dr. William M. Scholl College of Podiatric Medicine, and School of Graduate and Postdoctoral Studies. Visit at http://www.rosalindfranklin.edu/ and http://www.lifeindiscovery.com/.

Contact: Kathy Peterson
Rosalind Franklin University of Medicine and Science

Faster, Low Cost Sequencing Technologies Needed To Drive Era Of Personalized Medicine

DNA testing is transforming health care and medicine, but current technologies only give a snapshot of an individual’s genetic makeup. Any patient wanting a complete picture of their inherited DNA, or genome, would drop their jaw at the sight of the bill — to the current tune of $10 million or more charged for every human or mammalian-sized genome sequenced.

Now, with a grant award from the National Human Genome Research Institute (NHGRI), scientists at the Biodesign Institute at Arizona State University are expanding efforts to dramatically lower the cost of DNA sequencing.

The NHGRI, part of the National Institutes of Health (NIH), has set an ambitious target of $1,000 or less – a cost 10,000 times lower than current technology – to make genome sequencing a routine diagnostic tool in medical care. The reduced cost may allow doctors to tailor medical treatments to an individual’s genetic profile for diagnosing, treating, and ultimately preventing many common diseases such as cancer, heart disease, diabetes and obesity.

ASU chemist Peiming Zhang and his collaborator Jian Gu have been awarded a $897,000 grant under this program for an ambitious DNA sequencing project that combines physics, chemistry and nanotechnology with engineering. The researchers have been charged with the daunting task of shrinking down the 13 year, $2.7 billion Human Genome Project to days.

“If you want to develop a technology to sequence an individual genome for $1,000, you have to think about using nanotechnology,” said Zhang, associate research professor in the Center for Single Molecule Biophysics at the Biodesign Institute. “The technology is available now to pioneer a new approach to sequencing.”

Much like the computer industry, DNA sequencing technology is driven by the mantra of faster, cheaper and more reliable. In the past generation, sequencing costs have fallen 100-fold, from roughly a dollar a DNA base to a penny, but are still far out of reach for the public.

Zhang’s technological vision would enable scientists to sequence billions of base pairs of DNA in a single day. This is the size of an average mammalian genome and is approximately 10,000 times more bases per day than can be sequenced using current technologies. By increasing the speed of sequencing and reducing its cost, genetic research may develop a more significant role in everyday medical practice.

In Zhang’s sequencing project, billions of base pairs of genomic DNA could be sequenced on a single, cookie crumb-sized one centimeter by one centimeter chip. The technique uses hybridization, a process of joining two complementary strands of DNA, to sequence DNA by applying a sample to single stranded DNA probes attached to a chip.

An atomic force microscope (AFM), like a caffeinated speed reader, can then rapidly scan the surface of the chip to see where DNA from the sample has hybridized to the probes. Wherever sample DNA binds to the probes, the sequence is registered.

“Traditional approaches to sequencing by hybridization are limited by the number of probes that can be placed on a chip,” said Jian Gu, a research staff member in the Center for Applied NanoBioscience at the Biodesign Institute and co-leader of the project.

By using nanoprinting techniques developed by Gu, the researchers hope to increase the number probes they can fit on a chip. “Right now, we have a mechanical printing technology that could put down billions of probes on a chip surface at very low cost,” said Gu.

It is estimated that a single base pair can be sequenced for every DNA probe, which means that optimizing the nanoprinting process is critical to the goal of a $1,000 genome, according to Zhang.

The researchers’ first goal is a proof of principal for their approach. They plan to synthesize a universal DNA nanoarray on a 100 micrometer by 100 micrometer chip, about the size of a dust mite, by 2009.

The award to Zhang and his team was one of nine grants given by the NIH to achieve the $1,000 genome goal. Zhang’s effort also joins two other ASU research teams, led by Stuart Lindsay and Peter Williams, who have more than $2 million in other DNA sequencing projects funded at ASU.

“There are currently only 36 grants in the entire NHGRI sequencing program, so it’s quite remarkable that ASU has three of them, which is almost 10 percent of the program,” Williams said.

Williams, professor of chemistry and biochemistry, is working on a $100,000 genome project, part of the five-year goal of the NHGRI to drop the current price to a hundredth of the cost. His goal is to selectively sequence genes known to be involved in disease in a matter of hours, and for a few hundred dollars.

Lindsay, who is director of the Biodesign Institute’s Center for Single Molecule Biophysics, is engaged in a different separately funded $1,000 genome project. Lindsay is threading DNA through a molecular ring, in this case a sugar called cyclodextrin, that can read the DNA sequence by measuring the differences in friction as the molecule is pulled through the ring.

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The Biodesign Institute at ASU combines research in biology, engineering, information technology, and cognitive science to accelerate discoveries into beneficial uses. The institute currently is pursuing innovations in healthcare, national security and environmental sustainability. For information, visit http://www.biodesign.asu.edu/.

Contact: Joe Caspermeyer
Arizona State University

Malaysia Could Face Increasing Number Of HIV Cases Without Amplified Control Efforts, Health Official Says

Nearly 300,000 Malaysia residents could become HIV-positive by 2015 unless increased efforts are made to reduce the spread of the virus, Ramlee Rahmat, deputy director-general for Malaysia’s Ministry of Health, said on Sunday, the AP/San Jose Mercury News reports. According to the AP/Mercury News, there are about 73,000 HIV-positive people living in Malaysia, 75% of whom are injection drug users and 7% of whom are women. Rahmat said the virus is spreading quickly among IDUs, women, fishermen, truck drivers and factory workers in the country (AP/San Jose Mercury News, 2/11). In addition, the government said that transmission through heterosexual sex is increasing and noted a “worrying trend” of increasing HIV incidence among women in the country (AFP/Yahoo! News, 2/11). According to Rahmat, the government last year launched a five-year national strategic plan to reduce HIV transmission. “We are taking this very seriously,” Rahmat said, adding, “If we carry out our plans effectively and the public cooperates with us, we will be successful in curbing the spread of the disease.” Rahmat added that the government has increased access to drug substitution therapy and needle-exchange programs among IDUs and has provided no-cost antiretrovirals for women and children at government clinics. UNAIDS in 2006 said that Malaysia was one of several countries in the Asia-Pacific region that risked an escalating number of HIV/AIDS cases among IDUs unless efforts were made to reduce the spread of the disease. According the health ministry, three people die daily from AIDS-related illnesses. The ministry last year warned that the spread of HIV could reverse the country’s development during the last 50 years, the AP/Mercury News reports (AP/San Jose Mercury News, 2/11).

“Reprinted with permission from http://www.kaisernetwork.org. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at http://www.kaisernetwork.org/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork.org, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.