$1.4 Million MDA Grant Will Help Develop SMA Drug

Repligen Corp. is proceeding with development of an experimental compound to treat spinal muscular atrophy, with help from a new MDA grant

RG3039 belongs to a class of drugs called "quinazoline inhibitors." Pictured: The drug (blue) bound to its target protein. (Photo courtesy of Families of SMA)
by Amy Madsen on December 15, 2010 - 9:08am

MDA has awarded a $1.4 million grant to the biopharmaceutical company Repligen Corp. to help advance the company’s experimental drug for spinal muscular atrophy (SMA) to phase 1 human clinical trials.

The drug, RG3039, has demonstrated potential throughout its early development, and is Repligen's lead therapeutic candidate for treatment of SMA.

The grant was awarded through MDA’s translational research program, which funds the transition of promising experimental drugs from preclinical development through the testing required to obtain government approval for marketing.

"MDA is excited to see RG3039 advance to clinical trials in the human population," said MDA Medical Director Valerie Cwik. "There's a profound sense of satisfaction in being able to support Repligen in its efforts to take this drug through the final stages."

MDA has worked on other projects with Repligen, including a current project to develop a treatment for the neuromuscular disease Friedreich's ataxia.

About SMA

SMA is a genetic disease that causes the muscle-controlling nerve cells (motor neurons) in the spinal cord to die off, resulting in weakness and eventual paralysis of voluntary muscles, including those involved in breathing.

The molecular basis of the disease is a flawed or missing SMN1 gene, which leads to insufficient production of SMN protein. (SMN stands for "survival of motor neurons.")

One or more copies of a nearly identical gene, SMN2, are also located on chromosome 5. Due to slight differences in processing during the protein-making process, however, the SMN protein derived from SMN2 instructions is shortened, unstable, and only marginally functional. Usually, but not always, individuals who have more copies of the SMN2 gene, and by extension, greater levels of the truncated and partially functional SMN protein, have less severe forms of the disease. (See SMA Research: The Curious Case of a Backup Gene.)

In addition, instructions from the SMN2 gene occasionally err on the helpful side, resulting in production of a full-length, fully functional SMN protein.

Increased SMN protein production from either a flawed SMN1 gene or modified SMN2 gene is expected to provide therapeutic benefits in SMA. 

About RG3039

Repligen’s compound RG3039 is designed to increase the amount of fully functional SMN protein produced by the SMN2 gene. It was licensed by Repligen from the patient organization Families of SMA, which fully funded and directed its preclinical development.

Repligen is currently working on manufacturing sufficient clinical grade quantities of RG3039 for use in testing, after which it will file an investigational new drug application with the U.S. Food and Drug Administration (FDA). 

Following FDA approval, Repligen plans to conduct two phase 1 human clinical trials designed to test RG3039's safety, tolerability and pharmacokinetics (the way the drug behaves in the body).

In the first trial, the drug will be tested in healthy adult volunteers; the second trial will test the drug in participants with SMA. 

In tandem with the two phase 1 human trials, researchers will conduct parallel studies in research mice to further refine the characteristics of the drug.

One particular aim of the mouse studies is to identify the optimum effective dose of RG3039 for humans. The scientists also will attempt to identify one or more reliable biological indicators, or "biomarkers," that can be used to precisely and reliably indicate the effects of RG3039 in patients.

Meaning for people with SMA

If the planned studies show potential for RG3039 to provide benefit in SMA, the drug likely will progress to phase 2 and 3 human clinical trials. FDA approval is necessary for the drug to be marketed for treatment of SMA.

Ultimately,  if RG3039 safely and effectively increases cellular SMN protein levels, it could dramatically change the course of SMA, said James Rusche, senior vice president of research and development at Repligen.

“It’s a very exciting proposition.”

[Editor's note: This article was updated 12-20-10 to clarify the important role of Families of SMA in the preclinical development of RG3039.]

Your rating: None Average: 3.8 (27 votes)
MDA cannot respond to questions asked in the comments field. For help with questions, contact your local MDA office or clinic or email publications@mdausa.org. See comment policy