Imma Perfetto
Cosmos science journalist
Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder that affects motor neurons – the nerve cells which govern voluntary movement.
Though exceedingly rare, some people undergo an “ALS reversal” in which they initially meet the diagnostic criteria for the disease but then experience a partial or full clinical recovery.
Now, researchers have identified the genetic factors influencing this unusual disease reversal. Patients with a single mutation were 12 times more likely to have experienced an ALS recovery than those without it.
The finding may help ongoing efforts to develop a treatment for ALS.
“With other neurological diseases, there are now effective treatments,” says Richard Bedlack, professor in the Department of Neurology at Duke University in the US and senior author of the new study published in the journal Neurology.
“But we still don’t have great options for these patients, and we desperately need to find things. This work provides a starting point to explore how biological reversals of ALS occur and how we might be able to harness that effect therapeutically.”
To understand the potential genes involved in these miraculous recoveries, researchers compared the genomes of 22 people who experienced ALS reversal with 2 independent groups of patients who experienced more typically progressive ALS.
They identified a single nucleotide variant (SNV) – a change in a single rung of the DNA ladder – in a gene called IGFBP7.
The mutation reduces levels of the IGFBP7 protein, which usually works to block the IGF-1 signalling pathway. IGF-1, insulin-like growth factor 1, is a hormone that has long been a target of interest in ALS research because of its role in protecting motor neurons.
Patients with fast ALS progression have lower levels of IGF-1, but clinical trials attempting to raise these levels therapeutically have been unsuccessful.
“This suggests that the IGF-1 pathway should be further studied as a potential target for future ALS treatments,” says co-lead author Jesse Crayle, from the Department of Neurology at Washington University in the US.
“While it may not be effective to simply give people IGF-1, our study indicates we might have a way to go about it differently by reducing the levels of this inhibiting protein.
“It is also possible that the prior studies with IGF-1 were just not adequately dosed or need to be dosed in a different way.”
