Researchers claim to have found a common cause behind the mysterious and deadly affliction of amyotrophic lateral sclerosis, better known as Lou Gehrig’s disease. The discovery could pave the way to new treatments for the devastating disorder whose victims include top physicist Professor Stephen Hawking.
Dr. Teepu Siddique, a neuroscientist with Northwestern University’s Feinberg School of Medicine whose pioneering work on ALS over more than a quarter century fueled the research team’s work, said the key to the breakthrough is the discovery of an underlying disease process for all types of ALS. The discovery could also help in developing treatments for other, more common neurodegenerative diseases such as Alzheimer’s, dementia and Parkinson’s, Siddique said.
The Northwestern team found the breakdown of cellular recycling systems in the neurons of the spinal cord and brain of ALS patients that results in the nervous system slowly losing its ability to carry brain signals to the body’s muscular system. Without those signals, patients gradually are deprived of the ability to move, talk, swallow and breathe. ALS afflicts about 30,000 Americans. With no known treatment for the paralysis, 50 percent of all ALS patients die within three years.
Siddique explained, “This is the first time we could connect (ALS) to a clear-cut biomedical mechanism. It has really made the direction we have to take very clear and sharp. We can now test for drugs that would regulate this protein pathway or optimize it, so it functions as it should in a normal state.” The announcement of the breakthrough is in Monday’s issue of the research journal Nature. The paper lists 23 contributing scientists, including the lead authors, Northwestern neurological researchers Han-Xiang Deng and Wenjie Chen.
Amelie Gubitz, a research program director at the National Institute of Neurological Disorders and Stroke, said the Northwestern research is a big step forward in efforts worldwide to conquer ALS. He said, “You need to understand at the cellular level what is going wrong, then you can begin to design drugs. ALS is a complicated problem, and Dr. Siddique’s research adds a big piece to the puzzle that gives us important new insights.”
A variety of proteins are present and perform different functions within cells, and Deng and Chen led research that discovered a key protein, ubiquilin2, in the ALS mystery. Ubiquilin2 in spinal and brain system cells is supposed to repair or dispose of other proteins as they become damaged. The researchers discovered a breakdown of this function in ALS patients. When Ubiquilin2 is unable to remove or repair damaged proteins, the damaged proteins begin to pile up in the cells, eventually blocking normal transmission of brain signals in the spinal cord and brain, leading to paralysis.
There are three forms of ALS, “familial,” which is hereditary and passed through genes; non-hereditary, which is called “sporadic”; and ALS that targets the brain, called “ALS/dementia”. Siddique was part of a study that made a major breakthrough in ALS in the early 1990s, discovering the "familial" gene that causes the disease within some families. That breakthrough came after he began an ongoing study 25 years ago of an East Coast family that has lost more than 20 members to ALS.
Experts in the UK said that the findings were significant. ALS affects an estimated 350,000 people around the world, including children and adults, with about half of people dying within three years of its onset.
Dr Belinda Cupid, head of research development at the UK's Motor Neurone Disease Association, said, “This is a big news story for motor neuron disease research. We've known for some time that the waste and recycling system in motor neurons is damaged, but this is the first time that there has been direct proof. This discovery provides researchers with an exciting new avenue to explore as they search for an effective treatment.”
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