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Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is characterized by a progressive degeneration of upper and lower motoneurons (MNs) with resulting motor and respiratory dysfunction. ALS has a prevalence of 2-3 per 100,000 people and is generally fatal within 1-5 years of onset. The cause of almost all occurences of the disease remains unknown. In ~90% of cases there is no apparent genetic linkage (referred to as sporadic ALS) but in the remaining 10% of the cases, the disease is inherited in a dominant manner (referred to as familial ALS; FALS), with mutations in the enzyme superoxide dismutase 1 (SOD1) comprising 15-20% of FALS cases. The hallmark of both forms is progressive muscle weakness, atrophy and spasticity, each which reflect the degeneration and death of upper and lower motoneurons in the brain and spinal cord. Additionally, 30% of the small interneurons (INs) in the motor cortex and spinal cord also degenerate. Currently many different agents are being tested in the ALS animal models to evaluate their possible neuroprotective properties and usefulness in treatment of ALS in humans. Unfortunately, few of these agents result in more than a modest change in survival. It was recently shown that ES cell can be differentiated into MNs in vitro, extend axons into the periphery and form connections with muscle targets in vivo. This heralds an opportunity for cell replacement as a future therapy for ALS. An optimal scenario might be transplantation of healthy ES cell derived MNs as well as INs to patients with ALS in combination with neuroprotective agents to increase survival of both the transplanted cells as well as the endogenous cells remaining in the patient. We are currently evaluating the integration and effect of ES-cell derived MNs and INs as well as primary embryonic spinal cord precursors after transplantation into the SOD1G93A rat model of ALS. Grants ALS Association Grant Award: Gene Expression Profiling of Motorneuron Nuclei Displaying Differential Vulnerability to Neurodegeneration in the SOD1G93A Rat
Links ALSA Journal update: ALS related science and medicine (July 2005)
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