Researchers found that the supplement prevents strokes in patients with rare genetic disease

Researchers at Children’s Hospital of Philadelphia (CHOP) found that a widely used nutritional supplement can significantly reduce the risk of fatal strokes caused by a rare genetic disease. In addition, the findings suggest that the supplement can be used to block precipitation and stop the formation of amyloid plaque deposits, a common feature found in severe forms of dementia. The results were published online today by the magazine. Nature Communications.

The findings revolve around a genetic disorder known as hereditary cystatin C amyloid angiopathy (HCCAA). HCCAA is part of a group of diseases in which amyloid proteins accumulate and deposit on the walls of blood vessels in the central nervous system. Most people with the leucine variant hCC glutamine (L68Q-hCC) that causes this disorder suffer strokes and hemorrhages in their 20s, leading to paralysis, dementia and death as these strokes become more frequent. Amyloid deposits seen in HCCAA cases are implicated in a wide range of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, Creutzfeldt-Jacob and Huntington.

“Although this is a rare disease, most patients diagnosed with HCCAA die within five years of their first stroke, so there is an incredible need to study this genetic disease and find effective treatment options,” said Hakon Hakonarson, MD, Ph .D., Director of the Center for Applied Genomics at CHOP and lead author of the study.

Since the formation of amyloid-producing proteins is already implicated in HCCAA and other diseases, the researchers studied whether drugs that reduce the aggregation of these proteins have the potential to reduce toxic oligomers, or polymers composed of a few different molecules. To properly study this strategy in HCCAA, the research team created cell lines that express wild-type and mutant L68Q hCC and then tried to non-toxicly interfere with the aggregation of amyloid-producing proteins. The researchers also studied a supplement called N-acetyl-cysteine ​​(NAC), which is sometimes prescribed to break up lung mucus and has also been shown to protect against toxic liver damage caused by an overdose of paracetamol, to determine if there was an effect on hCC amyloid protein deposits on skin biopsies of patients with a known diagnosis of HCCAA.

The researchers found that treating these cell lines with NAC breaks the oligomers into monomers, or molecules that have been separated from the chain that joins them. This, in turn, helps to prevent the formation of amyloid-producing proteins that lead to amyloid deposits involved in strokes and other deficiencies. The researchers also performed skin biopsies on six patients with the L68Q-hCC variant taking NAC to determine levels of amyloid-hCC protein deposits after treatment. Five of the six patients observed a 50% to 90% reduction in L68Q-hCC levels, suggesting that this variant is a clinical target for reducing agents such as NAC. This proof-of-concept study led to a clinical trial to see if these results are seen in a larger cohort of patients.

“Amyloids cannot precipitate without aggregating, so if we can prevent this aggregation with a drug that is already available, then we can make an incredible difference in the lives of these patients,” said Hakonarson. “In addition, since we already have genetic tests available to identify these patients, we could conceivably give this treatment early in life and potentially prevent the first stroke from occurring.”