Parkinson’s Disease is the second most common neurodegenerative condition, affecting 35 million people globally. Currently without a cure, researchers from Stanford University have identified a molecular defect common to all people with the condition that may help pave the way for early diagnosis and new treatment options.
In a study published in Cell Metabolism, researchers collected skin samples from 83 people with Parkinson’s, five asymptomatic close relatives thought to be at high risk of developing the condition, 22 people with other movement disorders and 52 healthy control subjects. Extracting the fibroblasts from the skin samples, they then cultured them in petri dishes and put them under stress to damage their mitochondria. Under normal circumstances, this process leads to the removal of Miro, an adaptor molecule, from damaged mitochondria, so they may then be repaired by the body (Hsieh: 2019).
Although Miro was successfully removed from damaged mitochondria in the control group and those with other movement disorders, for those with Parkinson’s and their high risk relatives, the Miro remained. A clear indicator of how the early stages of Parkinson’s begin- by disabling the body from repairing damaged mitochondria, the researchers recognised that simple tests like this may help with early diagnosis of Parkinsons. Yet, they didn’t stop with this conclusion (ibid.).
Screening 6,835,320 molecules, they used software from Atomwise to identify 11 molecules possibly capable of binding to Miro to facilitate its separation from mitochondria, that were nontoxic, orally available and able to cross the blood-brain barrier. Testing these compounds on fruit flies for seven days, the researchers found that four of them significantly reduced their Miro levels without negative side effects. Furthermore, the researchers also tested one compound on fibroblasts from a patient with sporadic Parkinson’s disease, noting substantial improvements on Miro clearance in their cells after their mitochondria was damaged.
Although further research is needed to confirm the results, Xinnan Wang, the study’s senior author, “Our hope is that if this compound or a similar one proves nontoxic and efficacious and we can give it, like a statin drug, to people who’ve tested positive for the Miro-removal defect but don’t yet have Parkinson’s symptoms, they’ll never get it. (Stanford Medicine: 2019)”
Hsieh, Chung-Han et al: Cell Metabolism