Rare mutation that halves risk of Parkinson’s disease discovered

Parkinson’s disease researchers say they have discovered a genetic mutation in a small protein that could produce new treatments for the degenerative brain disorder. The relatively rare variant is primarily found in people of European descent — those who have it are half as likely to develop the disease.

“Our data highlights the biological effects of a particular gene variant and the potential molecular mechanisms by which this mutation may reduce the risk for Parkinson’s disease,” said first study author Su Jeong Kim , an adjunct research assistant professor of gerontology at the University of Southern California.

The study findings were published last week in the journal Molecular Psychiatry . Nearly 1 million Americans have Parkinson’s disease — a number that is expected to grow to 1.2 million by 2030, according to the Parkinson’s Foundation . Ozzy Osbourne , Michael J. Fox , and Neil Diamond are among the celebrities who have shared their Parkinson’s diagnoses.

The disease affects how people control their bodies, with symptoms including slow movement, tremors, stiffness, and difficulty walking. While studying the progressive disorder, a USC researcher in 2016 discovered SHLP2, a mitochondrial derived peptide (MDP). Mitochondria produce the energy needed to power the body’s cells — aging is associated with a decline in mitochondrial function.

MDPs have been shown to play a role in maintaining mitochondrial activity under pressure. Scientists have noted that levels of SHLP2, specifically, rise with the onset of Parkinson’s. But, as the disease progresses, most patients cannot produce more SHLP2. While screening thousands of people, researchers identified a highly protective SHLP2 variant found in 1% of Europeans that cuts the risk of developing Parkinson’s disease in half.

The SHLP2 variant is said to provide better protection against mitochondrial dysfunction. Senior study author Pinchas Cohen said the discovery “underscores the relevance of exploring mitochondrial derived microproteins as a new approach to the prevention and treatment of diseases of aging.” The benefits of the mutant form of SHLP2 were observed in human tissue samples and lab mice.

“These findings may guide the development of therapies and provide a roadmap for understanding other mutations found in mitochondrial microproteins,” Kim said..