MDA-Funded Team Tests Gene Therapy Against SMA

TUCSON, Ariz. Jan. 19, 2003 — In experiments on human cells, scientists funded by the Muscular Dystrophy Association have used gene therapy to replace the defective gene behind spinal muscular atrophy (SMA).

Each year, some 35,000 Americans are discovered to have the disease, which attacks muscle-controlling nerve cells (motor neurons) in the spinal cord. Infants born with the disease usually succumb to paralysis and respiratory failure within their first two years of life. Children and adults develop less severe forms of the disease, often losing the ability to walk and to breathe on their own.

All three types of SMA are caused by mutations in a gene that makes a protein called survival motor neuron (SMN).

Christine DiDonato, an MDA grantee and senior research associate at the Ottawa Health Research Institute (OHRI) in Ottawa, Ontario, was part of a team that used a virus to ferry the SMN gene into skin cells derived from people with SMA.

Although motor neurons are the ultimate target for the therapy, skin cells were ideal for testing it because they’re easy to obtain and grow in the lab, and they exhibit “one of the hallmarks of SMA,” said DiDonato.

Normal human cells, she explained, contain “gems” — areas rich in SMN and associated proteins — but the cells of SMA patients contain a reduced number of gems or none at all.

Working with virologist Robin Parks and molecular biologist Rashmi Kothary, scientists at the OHRI and professors at the University of Ottawa, DiDonato found that viral delivery of the SMN gene restored gems to the cells taken from people with SMA. Their study appears in the Jan. 20 issue of Human Gene Therapy.

This is a first step toward clinical trials of gene therapy for SMA, DiDonato said. “The next step is to go into animal models of SMA and see if we can correct the pathological defects that result from low intracellular levels of SMN.”

MDA is the nonprofit health agency dedicated to curing muscular dystrophy, ALS and related diseases by funding worldwide research. The Association also provides comprehensive health care and support services, advocacy and education. The Association's programs are funded almost entirely by individual private contributors.