Potential Gene-Replacement Therapy for Rare Genetic Condition in Development

Gene-replacement therapy successful in mouse model with spinal muscular atrophy with respiratory distress.

Researchers have developed a gene-replacement therapy that can potentially be used to treat and control spinal muscular atrophy with respiratory distress type 1 (SMARD1).

SMARD1 is an extremely rare genetic condition with a high mortality rate that targets the spinal cord, which leads to atrophy of muscles and paralysis of the diaphragm. The disease is typically seen in children, according to a study published by Molecular Therapy.

The average life expectancy of a child diagnosed with SMARD1 is 13 months and there is currently no cure or treatment.

"Monogenic diseases like SMARD1, a disease that is caused by one gene, are ideal for gene therapy since the goal of the therapy is to replace the missing or defective gene," said researcher Chris Lorson, PhD. "Our goals for this study were to develop a vector that would improve the outcomes of the disease and for the vector to be effective in a single dose."

In the study, researchers developed a gene-replacement therapy and administered it to infant mice with SMARD1. The gene therapy is able to cross the blood-brain barrier and target neurons affected by SMARD1.

"One of the most remarkable aspects of this type of gene-replacement therapy is that it will last for an extended period of time," Dr Lorson said. "The ability of the therapy to cross the blood-brain barrier, a protective barrier that typically prevents toxins or microbes from entering the brain, opens the door for IV administration, allowing us to target motor neurons with a relatively non-invasive procedure."

Researchers found that in the SMARD1 mouse model, a low dose of this therapy improved muscle strength, protein expression in motor neurons, and life span.

Investigators are continuing to develop a suitable delivery system for the therapy, determining the exact dosing, when it would be most effective, and where it should be administered for the most effective outcome.