BioWorld International Correspondent
PARIS - Researchers at France's National Institute for Health and Medical Research (INSERM) obtained "encouraging" results from a trial in mice of a gene therapy for spinal muscular atrophy.
The therapy entailed the transfer of the cardiotrophin-1 (CT-1) gene, a neurotrophic factor, into the muscle tissue of mice suffering from the disease.
Spinal muscular atrophy is a neuromuscular disease caused by the mutation of the Smn gene on chromosome 5 and is one of the most common recessive autosomal diseases. It is characterized by the degeneration of motoneurons in the spinal cord, resulting in paralysis and early atrophy of nearby muscles, especially those in the pelvis, trunk, shoulders, arms and legs. At present, there is no treatment for the condition, which affects one in 6,000 newborn babies.
The INSERM researchers began by studying a mouse model of the disease, which indicated that the majority of motoneurons were present in the organism but did not function properly, if at all. The model pointed the way to possible therapeutic avenues for the pathology, highlighting in particular the potential therapeutic properties of neurotrophic factors. The researchers discovered that those factors, which ensure neuron survival and growth, could be used to slow the degeneration of motoneurons.
In the trial, an adenoviral vector carrying the CT-1 gene was administered by intramuscular injection into mice suffering from spinal muscular atrophy. The therapy effectively slowed the progression of the disease, resulting in longer survival times and improved muscle movement in the treated mice.
The research was carried out by two INSERM units - the Department of Genetics and Molecular Pathology at the Institut Cochin in Paris and the Molecular Neurogenetics Laboratory at the Genopole in Evry.
According to the head of the latter, Judith Melki, "the method of transferring the gene into the muscle enabled the compound coded by this gene to be delivered into the blood circulation on a continuous basis." It was the "first step toward developing therapeutic strategies for spinal muscular atrophy in man," she said, adding that the "gene therapy approach complements the laboratory's recently published work on the potential regeneration of muscle through adult stem cells."
The INSERM researchers plan to continue their work to determine the optimal dose of CT-1 to be administered, to look for ways of delivering the gene without using a viral vector, and to test the therapy in association with other neuroprotective drugs in order to amplify the therapeutic effect.