Families of Spinal Muscular Atrophy Collaboration with Nationwide Children's for Gene Therapy Development.

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Program Update 2010 Families of Spinal Muscular Atrophy (FSMA) recently awarded a grant to the Nationwide Children’s Hospital at Ohio State University toward their Gene Therapy Development Program. This program works toward replacement of the entire SMN1 gene, and has the potential to be groundbreaking in the treatment of SMA patients.

Families of Spinal Muscular Atrophy (FSMA) recently awarded a grant to the Nationwide Children’s Hospital at Ohio State University toward their Gene Therapy Development Program. This program works toward replacement of the entire SMN1 gene, and has the potential to be groundbreaking in the treatment of SMA patients.

Previously, in the journal publication Nature Biotechnology. the Ohio State University group reported that their preliminary research had shown that a gene therapy can fully rescue SMA mice for normal function and lifespan by delivering the SMN gene to motor neurons through injection into the blood stream when administered within 5 days of birth in mice.
Importance of this Project

Dr. Brian Kaspar, Ph.D., explains the evolution of this exciting program, “Families of SMA funded a translational research project in The Kaspar Laboratory at Nationwide Children's Hospital and The Ohio State University to help answer an important question in our SMA gene therapy program. The project is a logical extension of our mouse studies. Briefly, we discovered that a gene therapy could cross the blood brain barrier and efficiently target motor neurons residing in the spinal cord at high efficiency.

“In the course of the mouse studies, we found a narrow window of therapeutic efficacy. Therefore, we designed a set of experiments in non-human primates to test the window of opportunity to target motor neurons. The goal is to test injections in various ages and determine the extent of motor neuron targeting.

“Continued studies over the next year on this FSMA funded project will help guide our abilities to increase SMN levels in older SMA patients.” In addition, the Kaspar laboratory is testing pre-clinical safety of SMN delivery in both mouse and non-human primates.

Families of SMA is collaborating with the Kaspar Laboratory to specifically target understanding biodistribution and the development of effective delivery of this therapy in primates. This step toward an IND application is important to move the program into clinical trials in humans. This project fits the funding goals of FSMA in unraveling the biology of SMA and moving quickly toward developing a therapy for SMA.

Progress
These studies are providing the framework for initiating the regulatory studies required for filing an Investigational New Drug Application, in our efforts to initiate human clinical trials for SMA patients. Progress in the OSU Gene Therapy Program has:

  • Shown that Viral Vecor AAV9 delivers SMN1 gene to motor neurons effectively.
  • Demonstrated that when given within 5 days after birth provides significant benefit to severe SMA mice.
  • Defined the important steps toward an IND application:
  • Understanding biodistribution and developmental timing of effective delivery in primates
  • Formal GLP toxicity studies
  • Further exploration of efficacy in mice and other larger animals
  • FDA-compliant, large-scale manufacturing process for clinical grade material

Background
Gene Therapy is an approach to treating diseases by either modifying the expressions of an individual's genes or by correction of abnormal genes. Gene Therapy works by administration of DNA rather than a drug. In the case of SMA, gene therapy could take several approaches. The most likely approach would be to replace the lost SMN1 gene in cells. A second approach could be to use small pieces of genetic material, called oligonucleotides, to improve the functioning of the back-up SMN2 gene.

Funding Key Discovery Programs
FSMA’s critical role in research is investing in the discovery of safe and effective therapies for SMA. Our objective is to dedicate targeted funds towards programs such as this, which show great promise toward creating a treatment and cure for SMA. The Scientific Advisory Board of FSMA chose the OSU Gene Therapy Project for this reason.

"Families of SMA is very pleased to fund studies to help advance this very promising new therapy towards the clinic," said Jill Jarecki, Ph.D., Families of SMA Research Director. “A primary goal for FSMA is to help build a pipeline of diverse approaches for SMA therapeutics. This groundbreaking new Gene Therapy for SMA is a critical step in this process."

About Families of Spinal Muscular Atrophy
FSMA is dedicated to creating a treatment and cure for SMA by: Funding and advancing a comprehensive research program; Supporting SMA families through networking, information and services; Improving care for all SMA patients; Educating health professionals and the public about SMA; Enlisting government support a; Embracing all touched by SMA in a caring community. http://www.curesma.org.

At FSMA, expert and independent prioritization and oversight of research projects is critical. This approach ensures that FSMA funds only the most promising research, and that the funded projects are run in a professional and efficient manner under the guidance of world-class experts.

About the Kaspar Laboratory, Nationwide Children’s Hospital, Ohio State University
The Kaspar Laboratory remains committed towards finding a treatment and cure for SMA. The Kaspar Laboratory is working in collaboration with Dr. Arthur Burghes, Dr. John Kissel, Dr. Steven Kolb, and Dr. Jerry Mendell to advance this translational project.

Contact Information
Families of SMA
925 Busse Road
Elk Grove Village, IL 60007
Phone 800-886-1762
Fax 847-367-7623
http://www.curesma.org

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Laura Franzen

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