Gene Replacement Therapy Possible Treatment for Certain Spinal Muscular Atrophy

University of Missouri researchers have developed a gene replacement therapy for spinal muscular atrophy with respiratory distress type 1 (SMARD1). The therapy is able to cross the protective blood-brain barrier and target affected motor neurons in a non-invasive manner.

The research paper describing the remarkable development, “Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent”, was published in Molecular Therapy.

SMARD1, a rare genetic disease, characterized by muscle weakness and respiratory failure that usually begins in infancy, is caused by mutations in a single gene called  IGHMBP2.  The defective protein mainly affects alpha-motor neurons, cells localized in the brainstem and spinal cord that are responsible for muscle control movement. The average life expectancy of a child diagnosed with SMARD1 is 13 months. There is currently no cure or effective treatment.

Because it is caused by one gene, SMARD1 is an ideal target for treatment via gene therapy. After developing a vector to administer the one dose gene replacement therapy, researchers gave it to infantile mice with the SMARD1 diagnosis. Upon observation, they saw that the therapy successfully crossed the blood-brain barrier and targeted motor neurons affected by the condition. Furthermore, the low dose therapy resulted in significant improvements in muscle strength, protein expression in motor neurons and a life span extension in the SMARD1 mouse group.

“One of the most remarkable aspects of this type of gene-replacement therapy is that it will last for an extended period of time,” senior author Dr. Christian L. Lorson, said in a news release. “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.”

The team now hopes to study which stage of the disease should receive the therapy,  the exact dose of the vector used to transmit the drug, and the most appropriate body location to administer the drug.