August 29, 2006

The ALS Association Funds Studies to Clarify the Role of Inflammation in ALS

[QUICK SUMMARY: The ALS Association is funding a continued line of investigation that will build on new evidence that an aspect of inflammation may actually help rather than harm in the progression of ALS.]

The ALS Association is funding research that will follow up on unexpected findings that a player in nerve cell communication and in the tissue response to damage, a molecule called nitric oxide, may actually prolong life in mice that have many aspects of the human disease, amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease).

This project is funded through The ALS Association’s program to recruit and retain experts in critical areas relevant to ALS. Cold Spring Harbor Laboratories researcher Grigory Enikolopov, Ph.D., will expand on his findings on the action of nitric oxide by increasing or decreasing its production in the SOD1 mutant mouse model of ALS using available compounds that act on nitric oxide production.

The planned studies could help solve a key controversy over the role of nitric oxide in ALS. Clarity on the role of nitric oxide would contribute to the search for an effective ALS treatment.

Nitric oxide is basic to several nerve cell processes, such as cell to cell communication, response to damage, and the orderly removal of damaged cells called programmed cell death (apoptosis). Work to date by Enikolopov, funded by The Greater New York Chapter of The Association, has followed the logic that nitric oxide would be harmful to people with ALS, a notion supplied by findings in some but not all labs working with this molecule. But Enikolopov has instead found that removing nitric oxide from the picture does not help lab mice that model ALS.

Mice expressing the mutation associated with some forms of ALS crossed with mice lacking nitric oxide (a genetic knockout of nitric oxide production in nerve cells) did not survive longer in contrast to some earlier studies in other labs. Instead, Enikolopov’s team has now gathered evidence that this breeding strategy in fact produces accelerated death and that nitric oxide may be beneficial in mice with the ALS-linked mutation to copper-zinc superoxide dismutase (SOD1).

New studies will now seek to confirm if increasing nitric oxide production extends lifespan in the SOD1 mice. The investigators will see at which stage in the disease nitric oxide production will help most and which way of changing supplies of nitric oxide will work best. Drugs that are approved by the FDA for other conditions can change nitric oxide production or availability. So any evidence that one of these might work in ALS can be quickly translated into clinical trials in this disease.

The researchers have found an interaction of nitric oxide with the glutamate messenger system in the nervous system. Glutamate is also implicated in ALS, and this converging picture may help in designing new therapeutics that will help in the disease. For further information about the roles of inflammation and glutamate in ALS, click here and here.

To refer to the earlier Association studies funded on this topic, click here.