Metformin is a drug treatment for patients with type 2 diabetes that regulates sugar levels released by the liver. In a breakthrough discovery, the diabetes drug proves to be effecting in treating Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease.
Approved by the U.S. Food and Drug Administration (FDA), a recent study on metformin inhibiting the neurological disease was published in the journal Proceedings of the National Academy of Sciences. Dr. Laura Ranum wrote how she's been looking for a treatment to stop ALS.
ALS progressively attacks the neurons in the brain and spinal cord, resulting in a gradual decline in motor skills. Some notable cases include the New York Yankees baseball player Lou Gehrig and Stephen Hawking. Currently, there are over 30,000 Americans with ALS where life expectancy after the time of diagnosis is only up to five years.
Genetic Mutation
The disease is a result of the gene chromosome 9 open reading frame 72 (C9orf72) mutating. This genetic mutation causes frontotemporal dementia, resulting in the deterioration of cognitive functions such as emotional control and increasing apathy.
Sometimes, ALS patients develop a combination of C9orf72 mutation and frontotemporal dementia, called C9-ALS/FTD. Genetically, the mutation creates rogue proteins called proteins repeat-associated non-AUG (RAN) proteins.
These rogue proteins accumulate in brain cells, causing the severe damage that is associated with ALS. In their research, they discovered how to switch off the rogue proteins. In mice models infected with C9-ALS, they found that destroying RAN proteins with antibodies resulted in the survival of motor neurons and improving their lifespan.
In a previous study, Nahum Sonenberg had discovered that metformin was effective against a disease with a missing protein called Fragile X syndrome. Sonenberg said in 2017, 'Traditionally, this disorder has been considered to be a developmental disorder, and that's always kind of closed everyone's mind to thinking that anything can be done once the kid is born. These sorts of findings change that thinking.'
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Metformin Treatment
By inhibiting a particular protein kinase R pathway, it was possible to stop the multiplication of genetic code which results in the decline of other cells. Dr. Tao Zu tested if metformin would lower RAN production.
Their experiments showed that the diabetes drug was effective against C9-ALS/FTD that produce RAN proteins. However, it is important to note that not all forms of ALS produce RAN proteins and that metformin would not be effective drug treatment for such cases.
Since metformin has become a common drug and has minimal side effects, human trials followed immediately. Dr. Ranum and a team from the University of Florida are currently in Phase 2 of metformin trials with C9-ALS patients.
All patients in the open-label trial will be receiving metformin as drug treatment. The team will then monitor RAN protein levels in their cerebrospinal fluid.
The next step would be to test the drug on a larger scale in comparison with a placebo treatment. 'We are especially excited about metformin as a potential treatment for C9-ALS/FTD and other repeat expansion disorders because by reducing RAN proteins, it could address a fundamental problem common to many of these diseases,' wrote Dr. Ranum.
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