New Diagnostic Marker can Detect Parkinson's Disease Early

Highlights:

• A cellular defect occurring almost in all Parkinson's patients contributes to injury and death of nerve cells (neurons) in the brain
• Identification of raised levels of Miro molecule, a biomarker in patients enables early detection of Parkinson's disease
• The biomarker helps test the capacity of specific drug molecules to reverse the defect and prevent the progression of disease

Scientists have zeroed in on a molecular defect present in almost all patients with Parkinson's disease (PD) and those at increased risk of developing the disease. The finding could enable early detection as well as testing of treatments that could prevent or retard the progression of the disease, according to the research team at Stanford University. "We've identified a molecular marker that could allow doctors to diagnose Parkinson's accurately, early and in a clinically practical way," said Xinnan Wang, MD, PhD, associate professor of neurosurgery. "This marker could be used to assess drug candidates' capacity to counter the defect and stall the disease's progression."

The findings of the study appear in the journal Cell Metabolism.

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Detection of Biomarker In Patients

• The study team obtained skin biopsy samples from 83 patients with Parkinson's disease, five close relatives considered to be at increased risk but asymptomatic at the time of the study, 22 persons diagnosed with various movement disorders and 52 healthy controls
• The team isolated fibroblasts, connective tissue cells found in skin and grew them in the lab in petri dishes.
• These fibroblasts were subjected to harsh test conditions with the generation of toxic metabolites that would make their mitochondria damaged and fatigued
• In normal persons, these damaged mitochondrial are removed by physiological cellular clearance mechanisms, before which the injured mitochondria have to be detached from their attachment to cellular proteins. This attachment is mediated by molecules called Miro molecules. Therefore, before removing the damaged mitochondria, the cellular mechanisms clear the Miro molecules
• In the test subjects, the team found that there was defective removal of Miro molecules in 78 of the 83 Parkinson's fibroblasts (94%) as well as all the "high-risk" samples.
• The clearance of fibroblasts from the normal controls and patients with other movement-disorders was normal

These findings indicate that levels of Miro molecule is elevated in patients with Parkinson's disease and can be a useful biomarker.

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Testing Specific Drug Molecules on Fruit Flies

• The team analyzed the efficacy of 6,835,320 small drug molecules, obtained from an existing database along with a biotech firm Atomwise Inc
• The software of the biotech company's at least predicted that 11 of these molecules could bind to Miro molecules to enable the separation from the mitochondria
• Additionally, these molecules were deemed to be nontoxic, available as an oral preparation and can cross the blood-brain barrier
• These compounds were fed to fruit flies for seven days, and found that four of them had significantly reduced Miro levels without any adverse effects
• One compound, which bound to the Miro molecule most exclusively was tested on fibroblasts from a person diagnosed with sporadic Parkinson's disease. There was a significant increase in Miro clearance in these cells after subjecting them to stress
• The compound was given to three different fruit-fly strains that were genetically altered to develop Parkinson's-like climbing difficulty.
• Giving the compound to those flies during their entire lifespan of 90 days preserved their climbing ability and protected their dopaminergic neurons, with no evident toxicity or adverse effects.

The findings of the study suggest that the biomarker may be able to detect Parkinson's disease early and can help to test out newer treatments that appear to be safe and effective.

Dr Wang feels that clinical trials of the promising drug/s can happen within a few years. He said: "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."

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About Parkinson's Disease in Brief

Parkinson's is a common neurodegenerative disorder affecting approximately 35 million people worldwide. Most are sporadic and 5%-10% are familial, running in families and inherited due to known genetic mutations. The cause of the disease is unclear and currently, there is no cure.

Symptoms of the disease include movement difficulties, issues with balance and posture, tremor, change in speech and rigidity of muscles. Treatments are available that check the symptoms but the condition is progressive. Several new treatments are being developed in the hope of a cure for this crippling condition.

Scope of the Study

• Early detection of Parkinson's disease
• Testing new treatments that are safe and effective

Stanford's Office of Licensing Technology has filed a provisional patent to use the main compound in this study in Parkinson's and similar neurodegenerative disorders. In fact, Dr. Wang has formed a company, CuraX to hasten the production of the drug.

References:

1. Scientists Discover Biomarker and Potential Treatment for Parkinson's - (http://med.stanford.edu/news.html)

Source-Medindia