Michelle Hastings, PhD, Assistant Professor in the Department of Cell Biology and Anatomy, in the Chicago Medical School of Rosalind Franklin University of Medicine and Science, has been awarded a five-year $1.68 million grant from the National Institutes of Health to support her research aimed at investigating treatments for the fatal children's disease, Spinal Muscular Atrophy (SMA).
Dr. Hastings is the lead author of a paper recently published in the journal Science Translational Medicine that reports the identification of a chemical compound with promise as a treatment for SMA. SMA, a leading cause of genetic infant mortality, is caused by a defect in a gene, SMN1, that encodes a protein called SMN, that is crucial for survival of spinal motor neurons.
SMA is one of the leading genetic causes of infant death. The disease affects as many as 1 per 6000 live births.
Those born with a mutation in SMN1 progressively lose the ability to move, swallow and breathe - the effects of which lead to eventual mortality, often before the age of two.
Humans have a backup gene, SMN2, that also makes SMN protein, but it is largely nonfunctional due to what molecular biologists term an "RNA splicing defect."
Dr. Hastings and her colleagues reasoned that if they could correct this defect, the backup gene might produce enough SMN protein to enable motor neuron survival.
Working in collaboration, Dr. Hastings, Dr. Adrian Krainer at Cold Spring Harbor Laboratory and Paratek Pharmaceuticals, with key pilot funding from the Families of SMA and later from the National Institutes of Health (NIH), discovered that a tetracycline-like molecule developed at Paratek, is able to correct the SMN2 splicing defect and improve production of SMN protein.
The novel compound they are investigating as a treatment for this devastating genetic disease so far improves splicing and human SMN protein levels in cells isolated from an SMA patient as well as in mice that carry the human SMN2 gene.
"The tetracycline derivative we have identified is an attractive candidate for therapeutic development as a potential treatment for the disease because it specifically targets SMN2 RNA splicing," said Dr. Hastings.
Dr. Hastings' NIH grant supports studies aimed at determining how the tetracycline-like molecule corrects the SMN2 splicing defect. These studies complement a multi-million dollar cooperative agreement from the National Institute of Neurological Disorders and Stroke (NINDS) awarded to Paratek, with Dr. Hastings as a key collaborator, that encompasses pre-clinical drug-development. Long-term goals of both projects are to develop the tetracycline-like splicing modulators as a therapeutic for children afflicted with SMA.
Dr. Hastings' research at RFUMS focuses on aberrant RNA processing that causes human disease and approaches to correct such disease-causing defects. In addition to her work on SMA she also has funding from the Deafness Research Foundation to study an RNA splicing defect that causes Usher syndrome in children, the leading genetic cause of combined deafness and blindness.
SOURCE Rosalind Franklin University of Medicine and Science