March 12, 2007

The ALS Association Expands Stem Cell Project to Characterize ALS Motor Neurons

[Quick Summary : New funding toward a project led by Harvard researcher Tom Maniatis, Ph.D., will support focused examination of gene differences for nervous system cells derived from mouse stem cells, apparently able to recreate the ALS disease process in lab dishes. Their approach should show exactly what molecular events are taking place with a precision not possible in other approaches.]

The ALS Association announced today new funding toward a project led by Harvard researcher Tom Maniatis, Ph.D., whose observations of motor neurons living in lab dishes could shed new light on what goes wrong in the human body with ALS (amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease). The studies are comparing the genetic, electrical and chemical properties of motor neurons derived from mouse stem cells. The new funding will support focused examination of gene differences for types of nervous system cells, derived from mouse stem cells, apparently able to recreate the ALS disease process in lab dishes.

Motor neurons growing in the lab with the genetic instructions from mice that simulate ALS (and in the future, human patients) may be showing the disease process more accurately than any other model of the disorder available today. Motor neurons are the cells that reach from the spinal cord to muscles and are the cells that die in the disease.

The first steps of investigation are taking place with stem cells from mice with and without the mutation that produces some inherited forms of ALS. The stem cells are prompted in the lab dish in which they are growing to form motor neurons or the supporting cells of the nervous system called glia. The derived motor neurons and glia have the genetic change that produces death of motor neurons in the mice and in some people with ALS.

With a motor neuron co-culture system successfully in place, the investigators are currently in a position to undertake systematic studies of the earliest events in ALS.  New studies with so called gene finder chips will hopefully serve to narrow the gap in understanding which genes differ in their activity during the development of ALS.

For genetic analysis, the gene chips, or microarrays, will survey which genes are working to make proteins within a cell hampered by the mutation.

The award is part of the granting program that The ALS Association uses to recruit and retain experts who will focus on finding effective therapies for the disease. The project brings together collective expertise in placing nuclei from adult cells into donated egg cells, as well as steering stem cells to become motor neurons and glia. Collaborators including the groups of Thomas Jessel, Ph.D., of Columbia University in New York, and Kevin Eggan, Ph.D., at Harvard. The teams will work with motor neurons generated from stem cells of mice with the so called SOD1 mutation. These mice express a change in the gene for the protein, copper-zinc superoxide dismutase, a mutation present in some of the ALS that runs in families.

This mouse model of the disease has provided a first step towards understanding the disease process but has not yet yielded a therapeutic solution. A more accurate and comprehensive laboratory model of the disease might dovetail with studies on the SOD1 mice to reveal a precise therapeutic target for ALS. The cell culture will allow the researchers to tell exactly which cells are responsible with a precision not possible in other approaches for watching gene expression in human disease.