Grant: Catalyst Grant: Invention and High-Risk, High-Benefit Research

Spinal muscular atrophy (SMA) is a devastating autosomal recessive disorder affecting newborns and young children. It is caused by reduced levels of the survival motor neuron (SMN) protein. Although normally expressed in all cells of the body, reduced expression of SMN results in degeneration of motor neurons, leading to muscle weakness and, in the case of severe disease, death. Currently, there is no effective treatment or cure. The goal of our research is to develop a novel treatment for SMA involving delivery of the SMN protein to deficient cells. To enhance uptake of the SMN protein by cells, we will generate a therapeutic protein containing the SMN protein attached to a protein transduction domain (PTD). Many studies have shown that PTD can efficiently "ferry" a variety of proteins across the cell membrane and into the cell. We will produce the PTD-SMN fusion protein using bacterial and mammalian expression systems, and purify large quantities of the protein using standard methods. We will verify the functionality of PTD-SMN protein therapy in tissue culture models of SMN-deficiency. Finally, we will deliver PTD-SMN to a mouse model of SMA and evaluate several measures for disease correction. Achieving our research goals will provide the first effective therapy for patients afflicted with SMA.