Cure SMA, the leading organization dedicated to the treatment and cure of spinal muscular atrophy (SMA), recently provided an additional $445,000 grant toward a gene therapy for SMA at Nationwide Children’s Hospital.

Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy at Nationwide Children’s, and his team have made promising strides toward therapies to treat SMA. This new award brings Cure SMA’s total funding for this program to $845,000: $745,000 for the CSF program and $100,000 for the systemic gene therapy program.

The number one genetic cause of death for infants, SMA is caused by a mutation in the survival motor neuron 1 gene (SMN1). Because of this mutation, the individual does not produce enough survival motor neuron (SMN) protein.

Advancing Therapeutic Approaches

Gene transfer may increase SMN levels by using a viral vector to deliver the SMN1 gene to affected cells. Dr. Kaspar’s laboratory discovered that adeno-associated virus serotype 9 (AAV9) had the unique ability to cross the blood brain barrier and the blood-cerebrospinal fluid barrier (CSF).

Dr. Kaspar and his team have studied two approaches for SMA therapy: an injection into a vein, a process known as systemic delivery which is currently in clinical trials, and delivery directly into the cerebrospinal spinal fluid (CSF), a process known as CSF-delivered gene therapy. The CSF-delivery project in SMA is a translational funding initiative to the Kaspar Lab at Nationwide Children’s Hospital provided by a collaborative funding initiative by The National Institutes of Health-National Institute of Neurological Disorders and Stroke and Cure SMA.

“We are excited about the milestones that have been reached thus far with Cure SMA funding, and look forward to seeing progression of the gene therapeutic program with our new round of funding to Dr. Kaspar. There is great potential for CSF-delivered gene therapy to be further advanced for patients with SMA,” said Jill Jarecki, PhD, research director, Cure SMA.

The new funding will now support regulatory filings with the FDA to begin a new clinical trial, studies to define dosing levels for a clinical trial focused on CSF-delivered gene therapy, and support screening potential patients for the trial and evaluating their responses to the therapy.

“We are excited about our progress to advance a CSF route of delivery to human clinical trials for SMA and we are grateful for the continued support from Cure SMA,” said Dr. Kaspar. “We were able to demonstrate remarkable survival rates with normal motor functions in our SMA animal models, and found significant targeting of motor neurons throughout the brain and spinal cord,” Dr. Kaspar explained. These results were published in a November 2014 article in Molecular Therapy, prompting the additional funding support from Cure SMA.

Advancing Treatment for the Entire Community

“A critical long-term goal of the Cure SMA drug discovery approach is to help identify treatments for SMA patients of every age, disease type, and stage. One of the most compelling aspects of CSF-delivered gene therapy is the promise it shows for reducing the amount of drug required for larger and older patients. This could eventually make the treatment accessible to a wider population,” said Dr. Jarecki.

The technology for both systemic and CSF-delivered gene therapy has been licensed to AveXis, a clinical stage biotechnology company.

Beginning in 2010, Cure SMA made a series of grants to Dr. Kaspar to study gene therapy, also called gene transfer. Using the data generated with Cure SMA funding on the CSF-delivery of the drug, Dr. Kaspar and his team were able to secure a $4 million grant from NINDS in 2013, to develop this delivery approach for human clinical trials in SMA.

Cure SMA would like to thank all those who have contributed funding for this particular program, including special gifts from The Michael and Chandra Rudd Foundation, The Miller McNeil Woodruff Foundation, and The Jacob Isaac Rappoport Foundation.