A new powerful class of antioxidants may provide relief from Parkinson’s in the future.
The medication, called synthetic triterpenoids, blocked development of Parkinson’s disease in an animal model.
The trial is discussed in the journal Antioxidants & Redox Signaling , as authored by Dr. Bobby Thomas, a neuroscientist at the Medical College of Georgia.
Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.
Researchers know that stressors from a variety of sources, be it trauma, insect bites or the simple aging process increases oxidative stress causing the body to respond with inflammation — as a part of the natural healing process.
“This creates an environment in your brain that is not conducive for normal function,” Thomas said.
“You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”
Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.
“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”
Researchers looked at a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids to be the most effective on Nrf2.
Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.
Researchers found that in both human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids.
Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage.
The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.
Researchers are now studying the impact of synthetic triterpenoids in an animal model genetically programmed to acquire PD slowly, as humans do.
Source: Medical College of Georgia