Evaluation of a Small Molecule HGF Mimetic as an ALS Therapeutic


To test the efficacy of a novel neuroregenerative/neuroprotective compound in a small animal model of amyotrophic lateral sclerosis (ALS)

Anticipated Impact: 

A potential treatment for a devastating, fatal disease


Amyotrophic lateral sclerosis (ALS, also called Lou Gehrig’s Disease) is a neurodegenerative and ultimately fatal disease that has only minimally effective treatments. A small molecule compound, MM-201, with valuable characteristics, such as retaining its effectiveness when taken orally and the ability to cross the blood-brain barrier, has been isolated and will be tested in a small animal model. The animal model reproduces many of the characteristics of ALS, and MM-201’s effectiveness in preventing neurodegeneration and restoring neural function, as measured by, e.g., muscle function and restoration of neurons, will be tested. Positive results will ultimately lead to trials in humans.

Collaborating organization:  M3 Biotechnology, Inc.

Amyotrophic Lateral Sclerosis (ALS) Treatment

Grant Update

Principal Investigator:
Joseph Harding
Grantee Organization:
Washington State University
Grant Title:
Evaluation of a small molecule HGF mimetic as an ALS therapeutic
Grant Cohort and Year:
2013 Proof of Concept (03)
Grant Period:
05/01/2014 - 04/30/2016 (Completed)
Grant Amount:
The goal of this project was to test the ability of a new Alzheimer's disease/ Parkinson's disease drug to impact the progression of disease in a mouse ALS model. Multiple endpoints were examined in the project to gauge the drug's potential. Although several of the endpoints, including survival time and overall motor function, revealed no positive effect of the drug, the drug did protect nerve cells in the spinal cord, which are responsible for movement, from death when examined midway thought the study. Moreover, we demonstrated that these same nerve cells that were saved were responding to the drug in a process called drug target engagement.Finally there was trend toward increased muscle strength in drug treated mice again at the earlier stages of the disease. There are many explanations for the overall lack of effectiveness in this mouse model-the simplest being that it just doesn't work. While this may be the correct conclusion the positive results suggest other possibilities. Perhaps the drug doses that were used in the study were wrong or the method of drug application was not appropriate to achieve therapeutic levels of the drug. The drug was given orally in this study. Recent research shows that although the drug does get into the body when delivered orally it does it poorly, especially in mice. Giving the drug subcutaneously (like insulin) or by vascular injection (like chemotherapeutic agents) may have been more effective. A separate potential problem relates to the limitations of the mouse model, which is unable to accurately mirror the human disease. Although the LSDF funded project has ended work is continuing to address the experimental limitations that may have negatively impacted the outcome of the study. Thus a final conclusion as to the therapeutic potential of this drug for ALS is still not resolved.

Impact in Washington

Location of LSDF Grantee
Locations of Collaborations/Areas of Impact

Legislative Districts:

Health Impacts

Amyotrophic Lateral Sclerosis (ALS) Treatment