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In vitro models and method of treatment for amyotrophic lateral sclerosis (ALS)

It has been impossible to isolate viable human motor neurons from patients or from postmortem samples to investigate the mechanisms leading to neural degeneration in ALS. A potential solution is to use embryonic stem cells (ESC) as a renewable source of cells carrying the disease genes for the study of disease processes. The Eggan laboratory of Harvard University has successfully developed in vitro models of ALS by differentiating mouse and human ESCs into motor neurons (Di Giorgio et al, 2007; Di Giorgio et al, 2008). These cells show pathogenic properties similar to those observed in ALS patients and in transgenic animals. Both systems will provide an inexhaustible supply of ALS-affected motor neurons for research. Also, they can be developed into high-throughput cell-based assays to screen for small molecules that promote survival of mutant SOD1 motor neurons in motor neuron diseases, such as ALS and spinal muscular atrophy (SMA).

Using the human ESC-based ALS model, the Eggan’s group has discovered that inhibition of signaling through the classic prostaglandin D2 receptor DP1 suppresses the toxic effect of SOD1 glia on motor neurons, hence providing a target for developing new methods of treatment for ALS.

Intellectual Property Status: Patent(s) Pending

Applications

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons of patients. Approximately 5,600 people in the U.S. are diagnosed with ALS each year. The incidence of ALS is two per 100,000 people, and it is estimated that as many as 30,000 Americans may have the disease at any given time. 80% of patients die within five years following diagnosis, where normally death is due to respiratory failure. To this day, there is no effective treatment for the ALS; the only drug currently approved by the FDA is a NMDA receptor antagonist (riluzole) that increases the rate of survival by 6 months. It is imperative to find new drugs for this disease and try to better understand the causes and mechanism of action, which are still largely unknown.

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