Working in coordination with the Cleveland Clinic Neurological Institute Center for Amyotrophic Lateral Sclerosis (ALS) and Related Disorders, Bright Side of the Road Foundation has identified the following avenues of research as ones we find both encouraging, and in need of financial support. (Please note: However encouraging some of these findings may be, at this time there exist no treatments for ALS that are proven, and there is no cure. Neither is the cause – or causes – understood. Our mission is one of great urgency.)

I.    BREAKTHROUGHS IN GENETIC RESEARCH

DNA study to identify human genes responsible for ALS

Given the mounting evidence that genetics, coupled with environmental triggers, could cause ALS, Dr. Pioro’s lab is extracting DNA from blood samples of ALS patients and conducting a gene array analysis to identify which genes cause or contribute to ALS.  The National Institute of Health is collaborating with Dr. Pioro and The Cleveland Clinic on this research.

DNA Study of Identical Twins

Taking this genetic pinpointing a step further, Dr. Pioro is also analyzing the genetic differences between two identical 45-year-old male twins, only one of whom has ALS.  The research here is to “fine map” their genetics and pinpoint differences that may have led to the development of ALS in one but not the other.

Genetic findings in Wobbler Mouse Model

In addition to the human studies, Dr. Pioro’s lab is using a unique mouse model — the “Wobbler” mouse — for studying the genetics of ALS, in contrast to many other labs, which have used a genetically engineered SOD1  mouse model.

Recent studies are showing that the SOD1 mouse model is not as effective, because certain genes that are pinpointed in human ALS are not present in the SOD1 mouse, whereas they are present in the Wobbler mouse.  Dr. Pioro’s Wobbler mouse research has identified certain “neuroprotective” effects of the Wlds  gene that may play a significant role in ALS.

This finding is of great interest to the ALS research community. Pinpointing this gene’s role in protecting motor neurons can lead to the development of treatments that can basically mimic this gene. Also, because the Wobbler mouse is so genetically similar to human beings, studies have identified other genes and mutations that play a role in human ALS.

Major Discovery of Possible Causal Link: “TDP-43” Gene

In 2008, neuroscience researchers found mutations of the TDP-43 protein in humans with ALS.

It is possible that this is not only present but is a cause of ALS. The abnormality of this protein is present in the Wobbler, but not the SOD1 or any other mouse model.

Coupled with this and other findings over the past several years, and by using this mouse model, the Cleveland Clinic’s genetic research is at the forefront of a breakthrough in understanding this deeply mysterious disease. As the causation puzzle unfolds, the Cleveland Clinic is well positioned to explore relevant treatments, and eventually, a cure, for ALS.

II.    NEUROIMAGING “CUTTING EDGE” TECHNOLOGY

In conjunction with the Cleveland Clinic’s Departments of Radiology, Neuroradiology, and Nuclear Medicine, Dr. Pioro’s clinical research lab has used the Clinic’s high- powered MRI imaging technology to identify and track brain regions where neurons begin to degenerate. This will enhance the Clinic’s ability to track the disease progression.  It not only enables researchers to detect ALS earlier, but to identify possible “pathways” from the brain to upper motor neurons that could be targeted for drugs to stop the dysfunction.  The evolving capabilities in neuroimaging, when combined with both genetic and drug research, place the Cleveland Clinic at the forefront of neurological research.

III.    CLINICAL DRUG TRIALS

Because of the Cleveland Clinic’s influence in the medical, research and pharmaceutical communities, and as a leading clinical research center, it has complete access to the most up-to-date drug trials and research for ALS, as well as other neurological diseases.  Of note this past year are the following drugs that are targeted for trials and are being used by patients under the FDA’s “compassionate use” policy:

• Arimoclomol – to be tested (Phase II-B) in the fall of 2008
• Ceftriaxone – an antibiotic that has been found to be neuroprotective
• Lithium – in conjunction with the only FDA approved drug for ALS (rilutec), a recent study in Italy of 44 ALS patients showed that it can reverse symptoms
• Baclofen – has shown to reverse symptoms when injected into spine

Note: Chelation is also being followed for certain patients that have sought treatment from other centers.  Chelation is a technique by which certain metals that are found to be elevated in ALS patients are reduced in the bloodstream through extraction.