ALS: From Silence to Scientific Breakthroughs
- PULSE MedTech
- Apr 8
- 5 min read
In the summer of 2014, millions of people dumped buckets of freezing ice water over their heads, laughing as they challenged their friends to participate in the challenge across many social media platforms. Behind all these videos, however, is a disease that slowly takes away an individual's ability to walk, speak, and eventually breathe. Among the people who were affected were Anthony Senerchia, Pete Frates, and Pat Quinn, who started this “ALS Ice Bucket Challenge,” which became one of the largest awareness campaigns for a disease that most people still do not understand: Amyotrophic Lateral Sclerosis (ALS).
ALS is a progressive neurodegenerative disease that affects about 2 to 4 people per 100,000 worldwide. This disease starts subtly and progressively gets worse. It may start in the form of a hand struggling to hold a pen, a foot dragging when walking, words coming out slower than before, until it eventually takes away the ability to breathe. Over time, these changes accumulate as motor neurons in the brain and spinal cord get destroyed. ALS currently has no cure and is fatal, making it a very difficult disease to have. I wanted to understand how a devastating disease like ALS works and what type of medical technology exists today to support individuals with this disease. To understand how ALS research has evolved, I spoke with Dr. John Ravits, a neurologist at UC San Diego who has spent decades studying ALS in both clinical and research settings.
Dr. Ravits’ path to ALS research began unexpectedly. Although he studied literature, his fascination with the brain led him to pursue neurology in graduate school. More specifically, Dr. Ravits specialized in neuromuscular disease, where he encountered ALS patients and made the devastating discovery that these patients received little attention from the medical community. As Dr. Ravits puts it, “The ALS patients were a neglected population…nobody really cared for them. They were overwhelmed, as you can imagine, frightened.” ALS is not just a disease, but a community of patients left behind.
As Dr. Ravits began seeing more and more patients, he noticed something puzzling: ALS didn’t look the same from person to person. Some patients lost the ability to speak first, and others experienced weakness in their foot or hand. Patients had varying initial symptoms. Noticing this, Dr. Ravits didn’t just want to study where ALS begins, but also how ALS spreads throughout the body, which is a vital part of our understanding of ALS today. Despite different starting points, Dr. Ravits was able to pinpoint the underlying biological pattern that governed the progression of ALS.
Shift in the ALS Field
A major turning point in the field of ALS came in the 1990s with the discovery of a mutation in the SOD1 gene, which is one of the first genetic links to ALS. This finding helped researchers distinguish between sporadic ALS cases (no genetic linkage) and familial ALS cases (family-inherited).
Dr. Ravits explains the genetics of familial ALS saying, “Anybody in a family has a 50% chance of passing it on to an offspring. So if you take a look at 100 patients with ALS, about 85% or so are sporadic. No family history out of the blue. All of a sudden, they get it. And then 10 or 15% were familial. So it was a pattern in the family, an autosomal dominant pattern. And of that 15%, about 20% have a mutation in SOD1. Turns out there are 60 genes that can cause it. But the SOD1 is one of the more common ones.”
At the same time, technology was also advancing. In 2003, Dr. Ravits began using the new laser capture technique in which a laser was able to extract a neuron from the spinal cord, and then the neuron could be investigated directly. Instead of using a model organism like a mouse, he could use this laser capture technique to study the neuron itself. These discoveries marked the beginning of a new era: one in which ALS research was no longer limited to describing what the disease looked like, but was now beginning to uncover why it happens.
Biological Player in ALS
Dr. Ravits’ research was able to contribute to the broader understanding of common biological mechanisms underlying neurodegenerative diseases. That key feature is the aggregation of abnormal proteins within neurons.
In ALS, particularly, a huge breakthrough came with the identification of TDP-43 as a major pathological hallmark, a protein that is associated with disease progression. Previous research has shown that TDP-43, which is located in the nucleus of a neuron, can end up in the cytoplasm, get chemically altered, and begin clumping together, causing the aggregation of proteins and neuron damage. To counteract the changes to TDP-43, Dr. Ravits looked towards a multitude of enzymes in this pathway as they may play a key role in preventing the clumping of proteins. Similar processes also occur in other neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases, suggesting that these conditions may share similar underlying mechanisms of disease development despite affecting different parts of the nervous system.
The Future of ALS Research
Looking ahead, Dr. Ravits foresees real progress in the form of promising gene-based therapies that aim to silence disease-causing genes or even viruses that can be engineered to deliver therapeutic genes to motor neurons in the brain and spinal cord. Rather than simply treating the symptoms of ALS, these new technologies serve as a beacon of hope to intervene at the root of the disease process. Although a cure to ALS is unclear currently, Dr. Ravits believes that what is possible in the near future is finding ways to halt the spread of degradation before it reaches critical functions like breathing. Another focus is to aid the nervous system’s natural repair system, potentially repairing some loss of function over time. “In the last 30 years, 40 years, all these treatments for immunologic disease, cancer, heart disease, GI disease have been developed, but neurology has not been able to develop much for therapeutics, and so we're entering into a time when there's really big heroic efforts to try to develop a therapy. So that's what the future, I think, is gonna be,” Dr. Ravits predicts.
When the Ice Bucket Challenge spread across the internet in 2014, it brought unprecedented attention to ALS. Since then, the efforts to combat ALS have been brought to the forefront. A lot of new technologies like gene therapy and viral-based therapies were developed from studying the potential causes of ALS, which are mutations in the SOD1 gene and TDP-43 protein abnormalities. Dr. Ravits hopes that his research into the biological causes and spread of ALS will aid in the development of therapies and ultimately halt the progression of ALS to control what was a previously unmanageable and devastating disease. †
Written by Editor and Staff Writer Lana Chuang (lachuang@ucsd.edu)
Work Cited
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Feb. 2026, pubmed.ncbi.nlm.nih.gov/41691309/.
Bryce-Smith, Sam. “TDP-43 Loss Induces Cryptic Polyadenylation in ALS/FTD.” National
Center for Biotechnology Information, U.S. National Library of Medicine, 21 Oct. 2025,
National Institute of Neurological Disorders and stroke. “Amyotrophic Lateral Sclerosis
(ALS).” National Institute of Neurological Disorders and Stroke,
Accessed 8 Apr. 2026.
Ravits, John. “Research Projects - Ravits Lab.” Ravits Lab, 9 Jan. 2026,
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