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.

A clinical trial entitled “Phase I/II Trial of Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy Type I (CARNI-VAL Type I)” is currently recruiting type 1 SMA patients up to 9 months old. According to study description on ClinicalTrials.gov, investigators aim “to test safety and evaluate early treatment intervention with valproic acid and carnitine in moderating SMA symptoms of Type I infants.” The detailed description goes on to say:

Valproic acid (VPA) is a medicine that has been used for many years to treat patients with epilepsy. Recent research suggests that VPA may be able to upregulate expression of a backup copy of the SMN gene in SMA patient cell lines. In addition, some preliminary data suggests it may prolong survival in animal models of SMA. Because VPA can deplete carnitine in children with SMA Type I, carnitine is added to help prevent possible toxicity.

In this multi-center trial, we will evaluate the effects of VPA/carnitine on infants with SMA type I. A variety of outcome measures, including assessment of safety, will be performed at each study visit to follow the course of the disease. The protocol includes two baseline visits over a period of two weeks, two clinical assessments on medication at 3 and 6 months, and then 6 months additional followup via telephone. Total duration of the study will be approximately 12 months.

This is an international, multi-center trial with study sites at:

• Johns Hopkins University in Baltimore Maryland
• Children’s Hospital of Michigan in Detroit
• Ohio State University Medical Center in Columbus
• University of Utah/Primary Children’s Medical Center in Salt Lake City
• University of Wisconsin Children’s Hospital in Madison
• Hospital Sainte-Justine in Montreal, Quebec, Canada
• Klinikum der Universität zu Köln in Cologne, Germany

For more details about the clinical trial, including eligibility criteria and contact information, click here. For more information about clinical trials in general, click here.

There’s an article in the latest issue of Neurology Today that covers the recent SMA Drug Summit. The summit, held in Washington D.C. and sponsored by Fight SMA, Families of SMA, and SMA Foundation, was held to foster the development of spinal muscular atrophy drugs that could be tested in clinical trials facilitated by the International Coordinating Committee.

The article includes an update on some of the drugs currently being tested that might show promise in treating SMA.

Click here to read the story, in PDF format.

FightSMA is funding a new study called “Prospective Phase I/II Study to Evaluate Effects of Sodium Phenylbutyrate in Pre-symptomatic Infants with Spinal Muscular Atrophy” or “STOP SMA” being conducted by the laboratory of Dr. Kathy Swoboda at University of Utah School of Medicine. The study will assess the safety, tolerability and potential efficacy of sodium phenylbutyrate (NaPB) in presymptomatic infants genetically confirmed to have SMA.

Sodium phenylbutyrate (NaPB) is a medicine that has been used for many years to treat patients with urea cycle disorders. Recent research suggests that NaPB may be able to prolong survival in animal models of motor-neuron disease. In addition, pilot data in human infants have suggested a possible benefit of early administration of NaPB. Since significant motor-neuron loss occurs in the first few weeks to months of life in the most severely affected infants, the earlier that NaPB treatment can be started, the greater the potential benefit in delaying onset and lessening severity of SMA symptoms.

For more information about this study, including eligibility criteria, and for links to other clinical trials, please visit the FightSMA website.

The Utah chapter of Fight SMA, Dylan’s Friends, alerted us an interesting article that ran recently in the Salt Lake Tribune.  At least one parent whose child is participating in a clinical trial for a treatment for spinal muscular atrophy type 2 is reporting what she believes is some success.  The trial, conducted by Salt Lake City neurologist Kathryn Swoboda, is looking into using the drugs carnitine and valproic acid to treat kids with the intermediate form of SMA.  Slated to wrap up in November, the study will help determine whether the drugs help salvage the nerves of children who have Type 2 SMA.

The parent quoted in the article said her son was stronger and has better mobility than before starting the medication.

Here’s an excerpt from the article…

For the past six months, all 90 children participating in the study have been on the drugs. During the first six months, however, half were on placebos. Neither the patients and their families nor Swoboda know which children - at six sites around the country - received the drugs in the first six months.

Valproic acid, approved by the Food and Drug Administration to treat epilepsy, psychiatric disorders, migraine headaches and pain, has also been shown to increase the protein critical to the health of motor neurons, or nerve cells in the spinal cord. The carnitine - a nutrient that helps the body turn fat into fuel - replaces that which is depleted by the valproic acid.

You can read the entire article on the Salt Lake Tribune website.

From today’s press release:

June 22, 2007, Libertyville, IL–Families of Spinal Muscular Atrophy (FSMA) is pleased to announce the selection of a Clinical Candidate for Spinal Muscular Atrophy through its program being conducted at deCODE chemistry. At the same time FSMA is now extending its contract with deCODE to continue work towards an Investigational New Drug (IND) application with the Food and Drug Administration. If successful, this would be the first novel drug designed specifically to treat Spinal Muscular Atrophy (SMA).

SMA is a genetic disorder with no current treatment that is the leading killer of children under two years of age. SMA is typically marked by the degeneration of voluntary muscle movement including the muscles that control crawling, walking, swallowing or breathing. This is an important step in the development of a small molecule therapeutic for this debilitating and normally fatal disease.

The lead compounds have shown the ability to extend survival in a mouse model of SMA. Due to this successful result the organizations have now been able to select a Clinical Candidate. This is the first time a novel compound specifically designed to treat SMA has reached this stage in drug development. Families of SMA has been funding and directing this particular program for the last 7 years. The total investment to date in this program alone is over $10M.

“Selecting a Clinical Candidate means that we are now preparing to run the safety tests required to apply to the FDA to begin clinical trials. This work will require funding of $2.5M and take almost 12 months to complete,” said Kenneth Hobby, Executive Director of Families of SMA. “If we are successful in this stage we would then look to start phase I clinical trials.”

“Excitingly, the program has identified drug-like compounds that act on SMA patient cells in culture to increase SMN2 gene activity and thereby the amount of functional SMN protein. The same compounds also have therapeutic benefit in a mouse model of a severe form of SMA. We are very pleased to see the project come this far,” said Mark Gurney, Senior Vice President, deCODE genetics and deCODE chemistry.

To read the full press release, click here.

The Charlotte Observer on May 6, 2007 ran an article about the Bolton Family who started FightSMA’s North Carolina chapter, Eleanor and Jack’s Buddies, in honor of their two children who have spinal muscular atrophy. John and Holly Bolton attended the FightSMA Annual Conference in Washington D.C. in April where they visited the offices of their representatives on Capitol Hill, including North Carolina’s Representative Sue Myrick.

From the article:

Their mission: Help kids in broken bodies
Couple back from Washington, where they sought U.S. funding to treat neuromuscular disorder
JOE MARUSAK

HUNTERSVILLE — Everyone told John and Holly Bolton not to worry, toddler Eleanor would walk soon enough. She didn’t.Eleanor, now 4, has spinal muscular atrophy, the Boltons learned.

The incurable disorder kills more infants than any other genetic disease. Son, Jack, 2, also inherited the responsible mutated gene. Many kids can still live a long life, but many don’t. “Fifty percent don’t live past age 2,” John Bolton said.

The disease affects kids’ ability to walk; only a few can stand up. It impairs their breathing, forcing them onto breathing machines. In more severe forms, lungs quit or fatal pneumonia invades.

The Boltons returned from Washington last week, where they and other parents lobbied for the proposed SMA Treatment Acceleration Act.

The legislation would establish a national clinical trials network to develop safe and effective treatments for SMA patients and possibly lead to a cure for the disorder that strikes as many as one in 6,000 infants.

“It’s so close,” John Bolton said. “If we had parity in funding from government, it would be a done deal.”

To read the full article, click here.

On Thursday, March 8, 2007, American Society For Experimental Neurotherapeutics (ASENT) devoted a section of their 9th Annual Meeting to the Fundamentals of Clinical Trials in Neurotherapeutics. Chaired by Wilson Bryan of the FDA and Bernard Ravina of University of Rochester, this day-long session included topics such as trial design, stages of therapeutics development, clinical trial statistics, and ethics of clinical trials.

FightSMA sponsored Dr. Jean Teasley’s attendance of the Fundamentals of Clinical Trials in Neurotherapeutics session. Dr. Teasley is a pediatric neurologist specializing in neuromuscular diseases and operative monitoring for neurosurgical procedures. She serves as Associate Professor in Virginia Commonwealth University’s School of Medicine’s Department of Neurology, Division of Pediatric Neurology and practices at Children’s Hospital in Richmond, Virginia where she treats spinal muscular atrophy patients.

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.