said Xinnan Wang, MD, PhD, associate professor of neurosurgery.
The findings of the study appear
in the journal Cell Metabolism
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
Testing Specific Drug Molecules on
- 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
- 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."
About Parkinson's Disease in Brief
Parkinson's is a common neurodegenerative disorder
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
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
- 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.
- Scientists Discover Biomarker and Potential Treatment for Parkinson's - (http://med.stanford.edu/news.html)