1874               

• French neurologist Jean Martin Charcot establishes amyotrophic lateral sclerosis as a distinct disease

1900s - 1940s             

• Cluster of ALS cases identified on Western Pacific
island of Guam

• High incidence of ALS noted on Kii Peninsula off
Japanese island of Honshu

• Yankees first baseman Lou Gehrig retires because of ALS in 1939

• Lou Gehrig dies of ALS in 1941

• ALS becomes widely known as Lou Gehrig’s disease

Lou Gehrig made all Americans aware of the devastation of ALS.

1950s               

Eleanor Gehrig, Lou’s widow, worked with MDA in its early years.

• Eleanor Gehrig, widow of Lou Gehrig, becomes MDA National Campaign Chairman

• MDA begins funding ALS research, mainly in basic nervous system physiology

1960s                    

• Biochemical studies of metabolism and nerve-to-muscle signal transmission begin

• Studies of microscopic structures of nerve and muscle cells continue

			By the 1960s, MDA-supported scientists were becoming highly knowledgeable about the microscopic structures of nerve and muscle tissues.

1970s               

• Studies of distribution of ALS cases on Guam and on United States mainland raise questions about environment and ALS

• Attempts to isolate viruses from ALS-affected tissue are unrevealing

• Studies of muscle and nerve structure and physiology in ALS continue

The 1970s led to further understanding of how nerve and muscle fibers interact.

1980s               

MDA research grantee W. King Engel at the University of Southern California in Los Angeles tested thyrotropin-releasing hormone in ALS.

• Clinical trials of thyrotropin-releasing hormone, a substance secreted by the hypothalamus that stimulates the pituitary gland, in people with ALS (not effective)

• Attempts to isolate viruses in ALS continue

• Possible role of polio virus infection in ALS reveals no role

• Clinical trial of virus-fighting chemicals called interferons (not effective)

• Studies of immune system proteins called antibodies and of the possible role of autoimmunity (an immune response to the body’s own tissues) begin

• Clinical trial of irradiation of lymph nodes, part of the immune system (not effective)

• Clinical trial of immunosuppressant cyclosporine (not effective)

• Studies of families with more than one case of ALS start

• Isolation of genes related to ALS attempted

• Clinical trial of growth hormone (not effective)

• Clinical trial of branched chain amino acids (not effective)

• ALS clusters investigated

• ALS genetics studied

1990s                            

• Clinical trial of immunosuppressant cyclophosphamide (not effective)

• Studies of the nervous system chemical glutamate begin

MDA-supported Stanley Appel  was among the first to suspect a major role for the immune system in ALS.

• Building on glutamate data, riluzole (Rilutek), a glutamate inhibitor, is approved for use in ALS

• Clinical trial of gabapentin (Neurontin), a glutamate inhibitor (not effective)
 
• Database for cases of familial ALS established

• Computer system for collecting genetic data in ALS established

• Factors in nerve cells that make them susceptible to ALS-related damage investigated

• Cellular waste disposal system studied

• Neurotrophic (nerve-nourishing) natural chemicals and spinal motor neurons examined

• Effect of immune system proteins taken from blood of ALS patients studied

• Superoxide dismutase 1 (SOD1) gene on chromosome 21 identified as the cause of an inherited form of ALS

• Mouse with mutated SOD1 genes developed as a model of ALS

• Building on knowledge that SOD1 has antioxidant properties, many studies of free radical activity
(which SOD1 combats) begin

• Clinical trial of SOD1 delivered into spinal fluid (not effective)

• Scientific working group established to evaluate proposed therapies for familial (inherited) ALS

• Genetic regulation of programmed cell death, a type of degeneration, investigated

• Study to identify ALS risk genes begins

• Magnetic resonance spectroscopy, an imaging technique, in the ALS-affected brain, investigated

• Experiments transfer neuroprotective genes into mice with ALS

• Investigations of the roles of insulin-like growth factor 1 (IGF1), ciliary neurotrophic factor (CNTF),
glial-derived neurotrophic factor (GNDF) and brain-derived neurotrophic factor (BDNF) lead to industry-sponsored clinical trials of each of these; results from two IGF1 studies were conflicting; none of the other drugs was effective

• Role of neurons (nerve cells) versus glia (supportive cells in nervous system) in ALS studied

2000s                            

Peter Carmeliet, working with MDA support at Flanders Interuniversity Institute for Biotechnology in Leuven, Belgium, probed the role of the VEGF gene in ALS.

• Scientists find that als in gene, when flawed, can cause a childhood form
of ALS

• Clinical trial of celecoxib (Celebrex), an anti-inflammatory drug (no benefit)

• Human stem cells aid rats with ALS

• Clinical trial of coenzyme Q10, an antioxidant that acts in cellular energy centers called mitochondria, begins

• Third clinical trial of IGF1 (Myotrophin) launched, with funding from National Institutes of Health

• Gene therapy with GDNF gene or IGF1 gene helps mice after muscle injection

• Clinical trials of minocycline begin

• Findings suggest people with ALS make a variant form of glutamate transport protein

MDA’s ALS translational research program contiues to help scientists move their promising findings from laboratories to clinics.

• Search for enhancers of glutamate transport identifies 22 chemicals

• Sodium phenylbutyrate and AEOL 10150 together extend life of ALS-affected mice longer than either drug alone

• Creatine and minocycline together extend survival in mice with ALS

• MDA hosts conference to mark 100th birthday of Lou Gehrig and speed clinical research

• Flaws in VEGF gene implicated as disease factor in some ALS populations

• Senataxin gene, when flawed, identified as a cause of juvenile ALS

• Industry-sponsored clinical trial of arimoclomol, studied earlier with MDA funding, shows drug is safe and well tolerated

• MDA-supported ALS registry goes online at www.alsconnection.com

• MDA launches ALS translational research program

Augie Nieto, a fitness industry pioneer who developed ALS in 2005, helped launch MDA's Augie's Quest research initiative in 2006.

• With Augie Nieto MDA launches Augie’s Quest, an ALS research fund-raising initiative

• MDA, through MDA’s Augie’s Quest, funds large-scale gene screening project; differences in DNA from ALS-affected and unaffected people found

• MDA’s Augie’s Quest research initiative and the ALS Therapy Development Institute of Cambridge, Mass., join forces to fund a $36 million ALS drug search

• National Institutes of Health funds clinical trial of ceftriaxone, putative glutamate transport enhancer, based on years of MDA-funded research

• Clinical trial of thalidomide, previously shown by MDA researchers to extend survival in ALS-affected mice, launched by pharmaceutical company

• Variations in enzymes that help detoxify nerve gas and pesticides linked to ALS

• Compound that blocks SOD1 gene instructions extends survival in ALS-affected rats; MDA funds toxicity studies needed prior to human clinical trials