Aug. 14, 2015
By Medical Discovery News
When the groundbreaking theoretical physicist Stephen Hawking was diagnosed with amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease at 21, he was given two years to live. Now he is 73 years old. How has he managed to survive this invariably fatal disease for so long? We may not have all the answers when it comes to ALS, but one study has brought us closer to understanding its cause.
ALS is a devastating, progressive neurodegenerative disorder characterized by gradual degeneration and death of motor neurons responsible for controlling voluntary muscles, resulting in the loss of all voluntary movement including the face, arms, and legs. The disease becomes life-threatening when the muscles in the diaphragm and the chest wall fail and the patient requires a ventilator to breathe. Most people with ALS die from respiratory failure three to five years after the onset of symptoms. Only 10 percent survive 10 years or longer.
One tragic aspect of ALS is patients usually retain their awareness, intelligence, taste, sense of smell, hearing, and touch recognition, making them acutely aware of their deteriorating condition. ALS is one of the most common neuromuscular diseases, afflicting 12,000 people in the United States. Some 90-95 percent of all ALS cases are sporadic, so they have no family history. The remaining cases, called familial ALS, have a genetic component.
While its cause has long been sought after, recently scientists conducted the largest genetic sequencing study of ALS patients thus far. The genetic information of nearly 3,000 ALS patients and over 6,400 control subjects were sequenced, leading to the identification of a new gene associated with ALS. It took a study of this size to detect such a rare gene variant, as it is only mutated in about 2 percent of sporadic ALS cases.
The gene, TANK-Binding Kinase 1 (TBK1), is involved in a cell system that degrades and recycles waste. Scientists are trying to link mutations in the gene with the accumulation of protein aggregates that are killing motor neurons. TBK1 is also important to the immune response. Scientists have long thought inflammation in the brain plays a role in ALS. Since TBK1 tamps down inflammation, a mutation in the gene could interfere with that function.
Researchers are also studying a gene, OPTN, that interacts with TBK1. Together they regulate cell waste disposal and inflammation. Scientists are experimenting on mice engineered with mutations in both genes to determine how they contribute to ALS. These models will also be used to develop future therapies. However, genetic profiling of ALS patients will be necessary to determine which therapy is appropriate depending on the gene that is mutated.
Since ALS can be caused by dozens of gene mutations, the more we can identify, the better scientists can understand their influence on the pathways that lead to this disease.
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Pamela K. Bond 