Abstract 2016

Motor neuron diseases such as spinal muscular atrophies (SMA) and amyotrophic lateral sclerosis (ALS) are among the most prevalent neuromuscular disorders. The main clinical presentations of SMA and ALS are progressive muscle weakness and atrophy. These symptoms are secondary to the degeneration of anterior horn cells in these diseases. A genetic basis has been proposed for SMA and familial ALS because there are genes that appear to segregate with each disease. However, the pathogenesis is not well understood and there is currently no effective therapy.

Our goal was to investigate the neuroprotective effects of growth factors such as glial-cell line derived neurotrophic factor (GDNF) om human spinal cord motor neurons by transferring growth factor cDNA into cells of the spinal cord. The gene transfer technique was used using replication defective adenovirus (ARV) containing the β-galactosidase (LacZ) or green fluorescent protein (GFP) reporter genes. Normal fetal human spinal cord was cut into 800µm transverse sections and maintained in a serum-free medium. Spinal cord slices were infected with 109-1010 PFU or ARVLacZ, ARVGFP, or AVRGDNF. One week after infection, robust gene expression was detected in cells with various morphologies. The infected cells include glia in the developing white matter and endothelial cells in the gray matter. β-galactosidase and GFP expression was also observed in cellular processes in the area of motor neurons. GDNF was detected using ELISA in the culture supernatant one week after cultures were infected with an adenovirus containing cDNA for that growth factor. This culture system has the potential to be a valuable model to study neurotrophic gene therapy for spinal cord diseases.

Funded by the Children's Research Center of Michigan and MH46815