I was assigned to read Tuesdays with Morrie for my English class this year, and I sat down and devoured the entire book in a few hours. This article isn’t a review of the book (that’s a story for a different time), but is based upon a central topic from that book, amyotrophic lateral sclerosis (ALS).
ALS is a progressive disease of the nervous system that affects nerve cells in the brain and spinal cord. ALS causes the loss of muscle control as the nerve cells, specifically motor neurons, that control muscles progressively degenerate. This makes the brain lose the ability to control muscle movement, which in turn causes muscles to atrophy, or waste away. ALS often begins with small symptoms like muscle twitches, weakness in the limbs, trouble swallowing or slurred speech. Eventually as the disease progresses and more neurons die, ALS sufferers lose control of the muscles needed for voluntary actions and may lose the ability to move, speak, eat, and breathe. While muscle movement declines, pain increases throughout the rest of the patient’s life. ALS risk increases with age, with a majority of patients being between sixty and eighty-five years old. Once diagnosed, the mean survival time for ALS patients is two to five years, but given the disease’s variability, this time frame can differ from only a few months to decades.
ALS was first discovered in 1869 by French neurologist Jean-Martin Charcot. ALS is also known as Lou Gehrig’s disease, after the professional baseball player, Lou Gehrig, who suffered from the disease. The late astrophysicist Stephen Hawking also had ALS and defied all odds to live fifty-five years after his diagnosis.
There is no cure for ALS. The first step to developing a cure for any disease is an understanding of the causes of the disease, and scientists and doctors do not yet understand the causes of ALS. Around ninety percent of all ALS patients have no family history or genetic mutations that are known to be associated with the disease. Additionally, veterans have a higher chance of developing ALS when compared to normal citizens, which further complicates the search for a cause. Currently, available treatments approved by the FDA can treat the symptoms of ALS and improve patients’ quality of life, but they are not cures.
Nevertheless, mutations in several genes have been found to be the cause of a small number of cases where there is a known family history of ALS. One of the mutated genes, copper-zinc superoxide dismutase (SOD1), is an enzyme whose role is to keep our cells healthy by breaking down toxic products. The defective SOD1 protein in ALS patients appears to be toxic to cells, damaging patients’ nervous system. The most recent drug to treat symptoms of ALS is Tofersen, which was approved in April 2023. Tofersen is an antisense oligonucleotide therapy, which means that it is a small string of DNA that will only bind with specific RNA molecules. These RNA molecules, if left alone, would produce harmful proteins. Tofersen targets RNA produced by a mutated version of the SOD1, preventing the mutant SOD1 protein from being made. Studies done on Tofersen in March 2024, showed that it resulted in slowed progression of ALS symptoms and no major symptoms. However, there appears to be an increased potential of a future autoimmune reaction from patients on this medication.
Another key component of the search for an ALS cure is the work being done on regenerative medicine. In 2022, Cedars Sinai’s ALS clinic conducted a clinical trial to test the safety of stem cell and gene therapy to treat neuron death. This trial was performed with eighteen patients, who each underwent a five-hour spine operation and other extensive tests. The research showed that the implantation of specialized stem cells called neural progenitors into the spinal cord can result in the release of a protective growth factor and protect neurons from death. The findings were published in September 2022, opening the door for more research into this type of therapy, to continually refine the method. Cedar Sinai is conducting additional trials that involve transplanting stem cells into patients’ brains, with the goal that patients can see positive results but with only a minor scar. These technologies are still new and risky, and it will take several more years before we can see the effects of stem cell transplant in treating ALS or other neurological diseases that are hallmarked by neuron death. However, they offer hope among the ALS community that a cure may be near.