August 9, 2006

Research Update — from ALSA’s National Office

The Milton Safenowitz Post-Doctoral Fellowships for ALS Research - Two Grants Awarded in August 2006

Roberta Friedman, Ph.D., ALSA Research Department Information Coordinator

Two young investigators are joining the field of ALS research under The ALS Association’s innovative program funded by The Milton Safenowitz Post-Doctoral Fellowship for ALS Research. This grant program recognizes and recruits gifted young scientists to the study of ALS.

One grant is to study a way to understand the dynamics within the long fibers of nerve cells, called the axons, as well as the process of orchestrated removal of damaged cells, called apoptosis, and will be investigated by Jinseo Rhee, Ph.D., who is working with Louis Reichardt, Ph.D., of the University of California, San Francisco, and the Howard Hughes Medical Institute. Rhee will investigate the function of a protein, abbreviated as p190RhoGEF, involved in the formation of new nerve cells during development.

This protein is at work in the process of apoptosis that prunes the developing nervous system to maintain and refine the proper network of nerve cells. Also, it helps in production of the structural proteins called neurofilaments that maintain the long fibers of motor neurons throughout life.  Mice that specifically lack the gene coding for production of p190RhoGEF in their motor neurons might show disrupted neurofilaments. Such mice could serve as a useful model of the disease process of ALS.

In the battle against ALS, repairing the damage with stem cell therapies is one of many promising treatment strategies. Pursuing this line of investigation, Monica Carrasco, Ph.D., has also been selected for The Milton Safenowitz Post-Doctoral Fellowship for ALS Research. Together with mentor Tom Maniatis, Ph.D., and collaborating experts in stem cell and motor neuron biology at Harvard in Cambridge, Mass., and elsewhere, Carrasco will establish lab cultures of stem cells derived from normal and SOD1 mutant mice. Studies to observe which genes are active or silent, and the electrical properties of the resulting cells, should provide insight into what characteristics of the motor neurons cause or reflect the disease state.

Following this mouse project, the investigators also plan to use available human embryonic stem cells that will be manipulated to contain the nucleus of cells taken from ALS patients. The latter technique, called nuclear transfer, will produce human motor neurons that can live in lab dishes. These cells should reflect whatever characteristics are present in ALS patients who provided the genetic material. This lab system should yield living human motor neurons that exhibit aspects of ALS not yet available for study.

These young investigators recruited to the study of ALS should produce useful new insights into the disease with suggestions for workable therapeutic interventions.