Target Investigator:	Wenlan Wang, M.D., Ph.D. Associate Research Scientist Nemours Biomedical Research
Collaborators:	Vicky Funanage, Ph.D., Nemours Biomedical Research Mena Scavina, D.O., Division of Neurology, Nemours
Mentors:	Robert Mason, Ph.D., Nemours Biomedical Research Jeffery Twiss, M.D., Ph.D., Nemours Biomedical Research

Spinal Muscular Atrophy (SMA) is a genetic disease caused by a missing or mutated gene called survival motor neuron gene 1 (SMN1). A hallmark of this disorder is death of motor neurons in the spinal cord and progressive paralysis. Approximately 1 in 40 people carry the diseased gene, and approximately 1 in 6000 babies are born with SMA each year, making SMA is one of the most common genetic causes of infant death. The SMN protein generated by SMN1 gene is critical for the survival of motor neurons. The focus of our research is to understand the how loss of SMN protein leads to death of motor neurons. Using cultured motor neurons and fibroblasts derived from patients with SMA, we are investigating the signaling molecules and pathways that lead to motor neuron death in SMA. Ultimately, these mechanistic studies will provide new treatment strategies to promote motor neuron health and survival and prevent muscle paralysis in patients with SMA.

Cellular model systems to study cell death in spinal muscular atrophy. Skin fibroblasts from SMA patients (left panel, stained for SMN protein) and motor neuron cultures (right panel, stained for a neuron marker protein neurofilament) are two kinds of cells that we use to understand how deficiency in SMN leads to increased cell death.

Related Publications:

Wang, W., Dimatteo, D., Funanage, V.L., Scavina, M. Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin-induced cell death. Mol Genet. Metabol., 85: 38-45, 2005.

Gomez-Curet, I., Robinson, K.G., Funanage, V.L., Crawford, T.O, Scavina, M., Wang, W. Robust quantification of the SMN Gene Copy Number by Real-time TaqMan PCR. Neurogenetics, 8:271-278, 2007.

Wang, W., van Niekerk, E., Willis, D.E., and Twiss, J.L. RNA transport and localized protein synthesis in neurological disorders and neural repair. Dev. Neurobiol. 67(9):1166-1182, 2007.

Wu CY, Gomez-Curet I, Funanage VL, Scavina M, and Wang W. Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin is p53-independent. BMC Cell Biol. 10:40, 2009.

Zhang HM, Robinson N, Gomez-Curet I, Wang W, and Harrington MA. Neuronal and network activity in networks of cultured spinal motor neurons. Neuroreport.20(9):849-54, 2009.