New Northwestern Medicine® research has provided another building block in the treatment of one of the leading causes of infant and early childhood mortality in the developed world, spinal muscular atrophy (SMA).
Although the genetic cause of SMA is well understood, there exists no cure for the hereditary disease, which affects the spinal cord and causes muscle weakness and breathing problems. Published in Human Molecular Genetics in coordination with a paper from Charlotte Sumner, MD, at Johns Hopkins University, the research by Christine DiDonato, PhD, assistant professor in pediatrics-human molecular genetics, has helped set the stage for future clinical approaches.
“Collectively, our work represents another step forward in the development of therapeutic candidates for the treatment of SMA, which have now reached testing in human subjects,” said DiDonato, a member of the Human Molecular Genetics Program of the Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center. “These findings are exciting, as our publications provide strong pre-clinical efficacy of the drug RG3039 across three SMA models of varying disease severity.”
SMA is caused by insufficient levels of the survival motor neuron protein. The goal of early SMA drug discovery programs has been to identify small molecules that will encourage the production of sufficient levels of the protein, thereby improving motor neuron function. The molecule RG3039 has proven to be a promising candidate, and the studies led by DiDonato provided dose selection and exposure estimates for the first studies of RG3039 in humans.
“Our results also showed increased survival as well as functional benefits in mouse models,” DiDonato said. “The functional benefits included muscle strength and endurance, which are greatly reduced in SMA patients.”
Starting her research more than two decades ago, before the gene responsible for the disease was known, DiDonato is especially excited that a major pharmaceutical company has licensed RG3039 for further clinical development.
“We’re very happy that our research was able to assist in the development of the molecule and contribute to dosage estimates,” she said. “It is reassuring that our results mirrored independent findings as we move closer to developing therapies for SMA patients.”
DiDonato’s work was supported by the Families of SMA, Repligen Corporation, and the National Institutes of Health.
Families of SMA funded and directed the preclinical development of RG3039, providing the investment for the first drug discovery program ever conducted specifically for the disease. In January, Pfizer licensed the program to develop potential treatments.