Scientists at the Stanford University School of Medicine in the US have identified a molecular marker that could enable doctors to diagnose Parkinson’s accurately, early and in a clinically practical manner.
The discovery points to the possibility of stopping the progression of Parkinson’s, the second most common neurodegenerative disease, which affects 35 million people globally.
Stanford University School of Medicine associate professor of neurosurgery Xinnan Wang said: “This marker could be used to assess drug candidates’ capacity to counter the defect and stall the disease’s progression.”
The scientists also identified a compound that appears to reverse the defect in cells taken from Parkinson’s patients. In animal models, the compound avoided the death of the neurons whose loss underlies the disease.
Wang’s group found a mitochondrial-clearance defect in Parkinson’s patients’ cells. The defect was the inability in removing Miro from damaged mitochondria.
In the new study, scientists secured skin samples from 83 Parkinson’s patients, five asymptomatic close relatives considered to be at heightened risk, 22 patients diagnosed with other movement disorders and 52 healthy control subjects.
Fibroblasts, cells that are common in skin tissue, were extracted from the samples. The cells were stored in petri dishes for undertaking a stressful process that messes up mitochondria.
The investigators identified the Miro-removal defect in 78 of the 83 Parkinson’s fibroblasts and in all five of the high-risk samples. However, the defect was not found in fibroblasts from the control group or from patients with other movement-disorders.
The scientists then partnered with biotechnology firm Atomwise to screen 6,835,320 small molecules, whose structures reside in a commercially available database.
Atomwise’s software predicted that 11 of those molecules would bind to Miro in a manner that would ease its separation from mitochondria and will also be nontoxic, orally available and able to cross the blood-brain barrier.
The researchers found that after feeding compounds to fruit flies for seven days, four of the molecules reduced the flies’ Miro levels without toxicity.
One compound, which appeared to target Miro most exclusively, was tested on fibroblasts from a patient with sporadic Parkinson’s disease, which led to enhanced Miro clearance in these cells after their exposure to mitochondria-damaging stress.
The compound was also fed to three different fruit-fly strains bioengineered to develop Parkinson’s-like climbing difficulty.
According to the scientists, administering the compound to the flies throughout their 90-day life spans produced no evident toxicity and avoided dopaminergic neurons’ death in all three strains and, in two, preserved their climbing ability.
https://www.medicaldevice-network.com/news/diagnostic-tool-parkinsons-diagnosis/
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