A chemical cousin of the common antibiotic tetracycline might be useful in treating spinal muscular atrophy (SMA), a currently incurable disease that is the leading genetic cause of death in infants. This is the finding of a research collaboration involving Adrian Krainer, Ph.D., of Cold Spring Harbor Laboratory (CSHL) and scientists from Paratek Pharmaceuticals and Rosalind Franklin University of Medicine and Science.
SMA is caused by mutations in a gene called Survival of Motor Neuron 1 (SMN1), resulting in a decrease in the levels of SMN protein in the motor neurons of the spinal cord - the cells that control muscle activity. Without the protein, these neurons degenerate, and infants born with the mutations progressively lose the ability to move, swallow, and breathe. There are no approved therapies for the treatment of SMA, which affects approximately 1 in 6,000 babies born in the United States.
The new molecule boosts the levels of SMN protein in cells by fixing a mistake in a cellular processing mechanism called RNA splicing. In a study that appears in the journal Science Translational Medicine on November 4th, the scientists report this fix in both mouse models of SMA, as well as in cells isolated from SMA patients.
Unlike previously identified molecules that stimulate SMN production, the tetracycline-like compound is a unique therapeutic candidate in that it is a small molecule that specifically alters RNA splicing by directly targeting the splicing reaction.
Further collaborative research will focus on pre-clinical drug development, and is being supported by a five-year, multi-million dollar cooperative agreement from the National Institute of Neurological Disorders and Stroke (NINDS) and by the Families of SMA funding program.