A small genetic change can sometimes make a huge difference. In fact, switching just one DNA “letter” out of the 3 billion complementary pairs that make up the human genome may explain at least some ALS reversals, based on new research published in the journal Neurology.
ALS reversals, where someone with a confirmed ALS diagnosis recovers significant lost motor function, are rare. In fact, only about 50 have been documented since the 1960s. But the reasons why these people recover when so many others do not could hold a key to unlocking new ways to halt or even reverse the relentless progression of ALS.
“Cases of recovery from ALS have been reported, but no one before me and my team has ever tried to study them,” said Dr. Richard Bedlack, the Stewart, Hughes, and Wendt Professor in the Department of Neurology at Duke University School of Medicine and senior author of the study.
This approach is not without precedent. A study of people infected with the HIV virus who never got sick showed that many of them had the same genetic alteration, which explained their resistance and helped researchers create a new drug that worked for everyone with HIV.
To find out if any similar genetic variations occur in people who recover from ALS, Dr. Bedlack collaborated with several other researchers at Duke Health and St. Jude’s Research Hospital to conduct a genome-wide association study (GWAS) that was supported in part by funding from the ALS Association.
The team compared the DNA of 22 people who had been diagnosed with either ALS or progressive muscular atrophy and then recovered to people of similar race and ethnicity whose disease progressed as expected (taken from the CReATe Consortium's Phenotype-Genotype-Biomarker study and Target ALS database).
What they discovered was a one-letter change in participants’ DNA that made them 12 times more likely to experience a reversal than those without the change. This small alteration is located in a gene called IGFBP7.
“No one ever thought this exact gene had anything to do with ALS, but it is involved in a pathway that has long been of interest in ALS called the insulin-like growth factor (IGF-1) pathway,” explained Dr. Bedlack.
Researchers have found that people with ALS who experience a faster progression have lower levels of the IGF-1 protein. Clinical trials aimed at raising IGF-1 levels have, so far, produced disappointing results, but this discovery provides a potential new approach.
“We already have a follow up study underway, and if that supports what we found, then we plan to launch a clinical trial targeting IGFBP7,” Dr. Bedlack said. “Time will tell, but my hope is that knocking down IGFBP7 might someday slow, stop, or reverse ALS.”
“These results are extremely interesting and are the direct result of our years’ of support of ALS genome sequencing and research,” said Dr. Kuldip Dave, senior vice president of research at the ALS Association. “By better understanding the genetics and underlying biology of this extremely variable disease, we can continue to accelerate the identification of new targets, the development of new treatments, and make ALS a livable disease.”
More information about ALS genes and mutations can be found HERE.
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Hello Claudia,
Research is happening now to see what may explain some ALS reversals.
Both my mother and father have been diagnosed with ALS. My mother is atypical, so her progression is very slow. My father’s is genetic, he was diagnosed 2 years ago and is now on hospice. My sisters and I are all carriers of the gene my dad has. Studies like these make a world of difference! Thank you for all you do!
We are so sorry to hear about what your family is going through! We hope that these studies do make a difference for your family and others.
My doctor told me that ALS is not generic.
Now I am reading that it is. Can you clarify this for me?
Hello Mary Ellen,
Approximately 5% to 10% of people living with ALS in the U.S. have family members who have also been diagnosed with the disease, making it probable that a genetic mutation has been inherited. About two-thirds of people with familial ALS have mutations in known ALS genes, indicating that more genes likely remain to be discovered.
To learn more about familial ALS, go to https://www.als.org/understanding-als/who-gets-als/familial.
Cool! Researchers are really diversifying their areas of attack. In terms of hope, stuff like this can go a long way for people with ALS.
Sister in law has ALS, and not doing well. Right now they trying to make her comfortable. She’s a DNR, and the family had hospice come talk with them.
Hello Stephen,
We are sorry to hear about your sister-in-law.
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