Michael Benatar, MBChB, DPhil, assistant professor of neurology at Emory University School of Medicine, has received the first clinical research award of its kind to study new therapeutic approaches for familial amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) through the ALS Association (ALSA) and the American Academy of Neurology (AAN). Funded by the two organizations through a new initiative called Translational REsearch Advancing Therapy for ALS, or TREAT ALS, the initiative aims to accelerate drug discovery and create clinical trials for ALS.
TREAT ALS was created in an effort to recruit talented and promising young clinicians to the ALS research field who propose innovative clinical research to test new therapies for the disease. The intent of this program is to foster the development and productivity of young clinician-scientists who have demonstrated the potential to make significant contributions to ALS clinical research. The award, totaling $155,000 over two years, will be granted to one clinical researcher each year.
Dr. Benatar, in collaboration with colleagues Jonathan Glass, MD, professor of neurology and Meraida Polak, RN, ALS research nurse, will use the funding to continue exploring the feasibility of a research study involving people with a strong family history of ALS and people who may carry one of the inherited genetic abnormalities known to cause ALS.
"If enough of these people can be identified, then we will be in a better position to design and implement a clinical trial in asymptomatic people at risk for developing the disease, with the end goal of determining whether it is possible to delay or prevent the onset of disease," explains Dr. Benatar.
ALS is a neurodegenerative disease that usually attacks both upper and lower motor neurons, producing progressive weakness of muscles critical for moving, speaking and eventually, breathing.ÊCognitive functions are usually left intact.
Familial or inherited ALS is very rare, with only 10 percent of those diagnosed inheriting the disease from a parent. Because the condition is so rare and the population of people is so small, testing therapies for familial ALS is extremely difficult.
The most common known cause of familial ALS is a mutation of the gene for SOD1 (superoxide dismutase). This mutation is believed to cause cells to make a defective SOD1 protein that is toxic to motor nerve cells. The SOD1 mutation, however, accounts for only 20 percent of inherited cases, or just 1 to 2 percent of all ALS cases.
"The best animal model for human ALS is the mouse model of SOD1-related familial ALS," explains Dr. Glass, an ALS researcher and the director of the ALS Center at Emory. "Many drugs have been tested in this model, with some showing significant success in improving disease outcomes. Unfortunately, however, none of these successes in ALS mice has worked to change the course of human ALS."
There has been no research, however, as to whether these treatments that seem to work in ALS mice carrying SOD1 mutations might also work in that rare subset of ALS patients that carry SOD1 mutations. According to Drs. Glass and Benatar, there is reason to suspect that people with familial ALS may respond differently to treatment than those with non-familial or sporadic ALS, hence the need for this important research study.
To date, all clinical trials have combined patients with both familial ALS and sporadic ALS (90 percent of all ALS cases are sporadic).
For over a year, the team has been advertising for people who think their family carries the disease, and the response has been overwhelming. So far, 147 families have come forward with derived pedigrees that cover 7,000 people.
"This effort helps us to identify the number of people at risk of developing familial ALS, and how many would be willing to take part in a trial to test treatment and reduce that risk," says Dr. Glass. "This research award, along with other funding, will help us move forward in our mission."
"It is an honor to have been selected to receive this award," says Dr. Benatar. "One of the major challenges one faces as a junior investigator is to find the necessary financial support and protected time to successfully launch a significant program of research. The AAN/ALSA fellowship offers just such an opportunity."