From the National Institutes of Health press release:

NINDS Names Dr. Petra Kaufmann Director of the Office of Clinical Research

The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, has named Petra Kaufmann, M.D., M.Sc., as director of its Office of Clinical Research.

Dr. Kaufmann is among the foremost experts in the design and management of clinical trials for neuromuscular disorders, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and mitochondrial diseases. In her new role, Dr. Kaufmann will lead the Institute’s efforts to increase the effectiveness of clinical studies by addressing issues such as optimal trial design, ethical safe conduct of trials, and challenges in patient enrollment.

“Dr. Kaufmann has experience in all phases of clinical research, from conducting laboratory investigation and studies on disease mechanism to serving in key leadership positions on several major multicenter trials,” said Story C. Landis, Ph.D., director of NINDS. “Dr. Kaufman’s outstanding skills and expertise will allow us to make the most of the scientific opportunities ahead and to have a significant impact on clinical neuroscience.”

Dr. Kaufmann said, “I look forward to supporting excellence in clinical research at NINDS so that the advances in neuroscience can be translated into better treatments for patients.”

To read the full press release, click here.

The National Institutes of Health (NIH) announced that Dr. Elias Zerhouni will be stepping down as NIH’s Director at the end of October. In an email to members of NIH’s extramural community, Dr. Zerhouni said, “I have had the unparalleled privilege of leading one of the great institutions in history,” and he included that he was leaving “to explore new opportunities and to devote much of my attention to writing.” Dr. Zerhouni has held the position at NIH since May of 2002.

“During his tenure, Zerhouni worked to lower barriers between disciplines of science and encourage trans-NIH collaborations,” said NIH’s press release announcing his departure. It went on to say “Zerhouni also led a major reform of the translational and clinical research system in the United States.”

To read the NIH press release and learn about Dr. Zerhouni’s accomplishments, click here.

The National Institutes of Health “is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.” It is composed of 27 Institutes and Centers, including The National Institute of Neurological Disorders and Stroke (NINDS) which established the SMA Project, “a model translational research program to accelerate the process of developing a safe and effective treatment for spinal muscular atrophy.”

A new website has been launched to, in the words of NINDS’s Dr. John Porter, “help parents understand the how-when-where-why of clinical studies and clinical trials in their children.” While not a spinal muscular atrophy (SMA) specific site, the videos and articles address many of the concerns that parents have when considering enrolling their child in a clinical trial, including SMA trials. Topics include “Importance of Research In Kids,” “Safety and Protections,” “Questions You Should Consider Asking,” and “Effects on the Family.”

The site was developed and made possible by the support of: National Heart Lung and Blood Institute (NHLBI), NIH, National Institute of Child Health and Human Development (NICHD), Best Pharmaceuticals for Children Act (BPCA), National Marfan Foundation (NMF), National Center for Research Resources (NCRR), NIH, and Gerber Foundation.

Check out the website by visiting: www.ChildrenAndClinicalStudies.nhlbi.nih.gov.

From the SMA Project:

Dear Colleague,

We have now posted the Supporting Documentation (including the Subcontract Agreement) for the SMA Project (http://www.smaproject.org) Request for Proposals (RFP) LD-090707. This RFP seeks to identify facilities to conduct preclinical testing of chemical compounds with the ultimate goal of submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA). We have also posted an updated version of the RFP (Attachment B in the RFP has been updated).

The RFP and Supporting Documentation can be accessed through the Solicitations page of the SMA Project website at http://www.smaproject.org/solicitations.html. Proposals are due by 3 p.m. Eastern Time on October 5, 2007.

Studies to be conducted under the resulting contract will include preclinical safety, toxicology, pharmacokinetic/dynamic, and biodistribution studies with candidate small molecule compounds that act as therapeutic agents for spinal muscular atrophy (SMA). While a broad range of Good Laboratory Practice (GLP) and non-GLP studies is anticipated, capability to conduct studies according to GLP is required. Science Applications International Corporation (SAIC), on behalf of the Government, shall supply the Offeror with a small amount of each candidate therapeutic compound. For certain compounds provided to the Contractor, SAIC may request a comprehensive Product Development Plan for services to be provided by the Contractor. Facilities will be evaluated on their past experience in preclinical, IND-directed small molecule development, as well as the proposed schedule and cost of studies required.

The National Institute for Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov/) launched The SMA Project: A Collaborative Program to Accelerate Therapeutics Development for Spinal Muscular Atrophy in September 2003. This program funds milestone-driven research aimed at identifying and rapidly developing a treatment for SMA, a paralyzing neurodegenerative disease of childhood.

From the SMA Project email service (June 8, 2007):

Dear Colleague,

I am pleased to announce the following funding opportunity for researchers in the field of spinal muscular atrophy (SMA):

The SMA Project (http://www.smaproject.org) expects to release a Request for Proposals (RFP) within the next 14 days to identify and fund facilities capable of providing the necessary research and development support for an Investigational New Drug (IND) submission in a format acceptable to the U.S. Food and Drug Administration (FDA).

The intention is to award a subcontract to a facility capable of conducting safety, toxicology, pharmacokinetic/dynamic, and biodistribution studies with candidate small molecule compounds that act as therapeutic agents for SMA. These studies will be done in partial fulfillment of the requirements for submitting an IND application to the FDA. Science Applications International Corporation (SAIC), on behalf of the Government, shall supply the Offeror with a small amount of each candidate therapeutic compound.

The Offeror will be required to prepare and deliver, for each selected therapeutic compound provided by SAIC for testing, a specific Test Implementation Plan including a proposed budget for the specific testing activities. Activities within the facility shall be highly coordinated with efficacy testing activities outside the facility by SAIC. SAIC shall require from the Offeror preclinical development data that are required by the FDA for filing successful IND applications.

Offers will be due approximately 28 days from the release of the RFP. Relevant documents will be available through the Solicitations page of the SMA Project website at http://www.smaproject.org/solicitations.html.

The National Institute for Neurological Disorders and Stroke (NINDS) (http://www.ninds.nih.gov/) launched The SMA Project: A Collaborative Program to Accelerate Therapeutics Development for Spinal Muscular Atrophy in September 2003. This program funds milestone-driven research aimed at identifying and rapidly developing a treatment for SMA, a paralyzing neurodegenerative disease of childhood.

Some comments on spinal muscular atrophy (SMA) this week from the National Institute of Neurological Disorders and Stroke (NINDS), which is part of the National Institutes of Health (NIH). SMA Foundation excerpted the below remarks made by NINDS Director Story C. Landis, Ph.D. while she was testifying in front of the Senate Subcommittee on Labor-HHS-Education Appropriations hearings this week:

A decade ago, spinal muscular atrophy (SMA) was one of hundreds of poorly understood inherited disorders that affect the nervous system, and the outlook for developing treatments was bleak. The discovery of the gene defect that causes SMA revealed a rational strategy for developing drug therapy. In just a few years, the NINDS SMA Project developed a detailed drug development plan and tested hundreds of new compounds in laboratory tests. Most recently, some of these potential drugs increased the amount of the critical missing protein to normal levels in cultured cells from patients who have SMA. The SMA Project is testing the effectiveness of these compounds in animals with SMA and assessing their safety to bring these potential drugs to clinical trials, offering significant promise for helping people who have SMA.

Research on SMA illustrates the path from gene to understanding to treatment. Researchers have now characterized well over 200 mutations that cause neurological disorders. For inherited ataxias, Batten disease, Down syndrome, Huntington’s disease, muscular dystrophy, Rett Syndrome, neurofibromatosis, and many other previously baffling disorders, researchers have genetically engineered animals that mimic the human disorder and then replaced genes, turned harmful genes off, turned up compensatory genes, or counteracted gene defects with drugs that target the affected cellular functions. In the future, application of these strategies to patients could preempt or even reverse the damage caused by gene defects. NINDS is aggressively pursuing opportunities to translate science advances such as these to treatments.

Read the full text of Dr. Landis’ testimony in PDF format here.

From the Department of Health & Human Services:

We are pleased to let you know that the National Institute of Neurological Disorders and Stroke (NINDS), through the NINDS Pilot Therapeutics Network (NPTUNE) program, is sponsoring two research studies to evaluate the safety and tolerability of sodium phenylbutyrate (NaPB) in subjects with Type I or Type II/III Spinal Muscular Atrophy (SMA). Both studies are Phase I dosage escalation studies that will assess safety, maximum tolerated dosage, pharmacokinetics, and bioactivity. It is anticipated that enrollment will begin soon.

Each study will be conducted in two stages. Stage 1 is the dosage escalation stage where maximum tolerated dosage will be defined. Safety, tolerability, and pharmacokinetics will be evaluated in this stage. Stage 2 will enroll different subjects who will receive NaPB at the maximum tolerated dosage identified in Stage 1. Safety, tolerability, and pharmacokinetics, as well as levels of SMN mRNA and protein, will be evaluated in Stage 2.

For additional information about these NPTUNE SMA studies, including eligibility criteria and contact information, please refer to our posting on www.ClinicalTrials.gov. The link for the Type I study is http://www.clinicaltrials.gov/ct/show/NCT00439218?order=3. The link to the Type II/III study is http://www.clinicaltrials.gov/ct/show/NCT00439569?order=4. Each participating clinical site was selected by competitive application process and will be listed on this website once ready to begin enrollment.

Science Daily published an article today about a promising new study at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) on mice that might one day lead to a treatment for spinal muscular atrophy in humans. Here’s an excerpt:

“This study shows that treatment can be effective when started after the disease appears,” says Kenneth H. Fischbeck, M.D., of the NINDS, who helped lead the new study. The finding is important because most children with SMA are diagnosed after symptoms of the disease become obvious, he adds. The report appears in the February 22, 2007, advance online publication of The Journal of Clinical Investigation.

The new study, directed by Dr. Fischbeck’s colleague Charlotte J. Sumner, M.D., at NINDS, tested a drug called trichostatin A (TSA) that is in a class of drugs called histone deacetylase (HDAC) inhibitors. These drugs increase the activity of certain genes in the body.

Previous studies have shown that HDAC inhibitors can increase the amount of SMN2 expression in cultured cells and that treating pregnant mice with an HDAC inhibitor can increase the survival of their babies with SMA. Preliminary clinical trials are now underway to test several HDAC inhibitors in children who have SMA. However, the drugs in those clinical trials are weak HDAC inhibitors with other biological effects that may limit their usefulness for treating this disease. More importantly, none of the previous studies has demonstrated that HDAC inhibitors can extend survival when delivered after symptoms appeared. In the new study, the investigators tested TSA, which is a potent HDAC inhibitor, in cells from SMA patients and in a mouse model of SMA. They found that the drug increased the amount of SMN2 gene activity in both the cultured cells and the mouse model.

Next, the researchers gave daily injections of TSA to the SMA mice, starting when the mice were 5 days old. By that time, the mice showed clear symptoms of disease: they were significantly underweight and they had a markedly impaired righting reflex, or ability to get on their feet after being placed on their backs. The treated mice lived 19 percent longer, on average, than mice that did not receive TSA. About three-fourths of the treated mice had improved survival compared to control mice. The other fourth showed no improvement.

The treated mice had less weight loss and better righting reflexes, walking ability, and forelimb grip strength than mice that did not receive TSA. Examination showed that the TSA-treated mice also had larger neurons in the spinal cord, thicker muscle fibers, and more muscle mass than untreated mice. “This is a proof-of-concept experiment,” says Dr. Sumner. “It clearly demonstrates that this treatment can ameliorate the disease in mice.” While the results are exciting, there are still no studies that have proven the effectiveness of HDAC inhibitors in humans, she cautions.

To read the entire article, click here.

To read the entire study report, click here.