Technologies

Summary

Amyotrophic lateral sclerosis (ALS) is a debilitating progressive neurological disease with very few medical options, most of which are only palliative. This imbalance in treatment options is due in part to a paucity of model systems that recapitulate the complex progression of ALS, therefore allowing the screening and evaluation of potential therapeutic agents against this disease. This technology is a method for co-culturing stem cell derived motor neurons with astrocytes. Further, this technology is able to model the neuronal death seen in ALS caused by a mutation in the SOD1 enzyme. As such this technology provides a robust platform for the evaluation of molecules with therapeutic potential for treating ALS.

Robust cellular growth and monitoring allows for rapid drug development

This technology overcomes much of the difficulty associated with neuronal cell culture by generating the neurons from stem cells. Thus, these cells can be readily expanded and seeded. Furthermore, neuronal viability can be monitored via fluorescence of GFP stably integrated into the stem cell's genome. To model the neural environment of ALS, stem cell derived neurons are grown on a monolayer of astrocytes expressing a mutant SOD1 protein which is specifically lethal to motor neurons. As such this technology is a robust cellular model of ALS. Implementation of this technology may result in a rigorous and robust system for the discovery of therapeutic molecules that prevent the death of motor neurons, potentially aiding in the development of curative therapies for ALS.

A working prototype of this technology has been developed and validated by comparison to primary neuron morphology and behavior.

Tech Ventures Reference: IR 2156

Publications

• Nagai M., Re D.B., Nagata T., Chalazonitis A., Jessell T.M., Wichterle H., Przedborski S. "Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons" Nature Neuroscience. 15 April 2007; 10 (5) 615-622.

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