Antioxidant delivery research aims to improve quality of life for patients

WSU collaboration on a pilot study using magnetic resonance spectroscopy produces first evidence that intranasal administration of the antioxidant glutathione can increase brain antioxidant levels in Parkinson’s disease.

Jeannie Padowski is a researcher at WSU Health Sciences in Spokane. She holds appointments in both the Colleges of Medicine and Pharmacy, and her main area of expertise is mathematical modeling of drug disposition in the central nervous system. This means Padowski studies and has extensive knowledge of pharmacokinetics and pharmacodynamics in relation to the central nervous system.

Glutathione deficiency has been documented in a variety of central nervous system disorders, including Parkinson’s disease. There is anecdotal evidence that supplementing glutathione can help alleviate symptoms, says Padowski.

Padowski recently teamed up with researchers at the University of Washington and Bastyr University Research Institute in Seattle, and looked at the effects of intranasal delivery of the antioxidant glutathione in patients with Parkinson’s disease. The intranasal delivery aspect of the project was particularly important because orally-administered glutathione is not well-absorbed. Intranasal delivery can sometimes be useful for targeting drugs to the brain.

The research team compounded a glutathione concentrate into a nasal spray and had study participants give themselves a single dose while undergoing MRI scanning. Using the brain scans of participants before the dose and at intervals in the following hour, the team was able to observe how well the treatment method delivered the antioxidant across the blood brain barrier. Padowski assisted with the data interpretation and analysis of the study.

“When you’re doing MRI, you’re using magnetic and radio pulses to generate an image of the body. That’s what people usually use MRI machines for—looking for tumors, injuries and such,” said Padowski. “But you can also program that same machine to apply the magnetic and radio pulses in a slightly different way, so that instead of generating an image, you generate a spectrum (a series of peaks along an axis), where each peak corresponds to an amount of a certain chemical in that tissue. This is usually only done for research purposes, it’s not a routine clinical procedure at this point.”

Part of Padowski’s previous research was implementation of this method for measuring glutathione levels in the brain, something that is challenging, she says.

“The use of magnetic resonance spectroscopy to observe changes in chemical composition of the brain over time is novel, and glutathione happens to be one of the few antioxidants you can detect with this approach,” said Padowski.

Their “proof-of-concept” study was the first of its kind to demonstrate a noninvasive, self-administered therapy that has potential for boosting glutathione levels in the brain. The investigators reported a 240% increase in brain glutathione within one hour of administration, and their results were published in the journal NPJ Parkinson’s Disease in February.

There were 15 people in the study, all with mid-stage Parkinson’s disease. Funding for the project came from the Michael J. Fox Foundation. Additional collaborators on the study included the Michael J. Crescenz VA Medical Center and the University of Pennsylvania School of Medicine in Philadelphia.

“Studies like this provide important information regarding how brain chemistry may change in response to disease and to therapeutic intervention. When successful, they can provide us with clues that could lead to the next treatment breakthrough,” said Padowski.

While increasing antioxidant levels alone will not stop Parkinson’s disease, glutathione administration has been reported to reduce Parkinson’s symptoms. This could provide Parkinson’s patients with a supplement to their standard drug therapy regimen that has the potential to improve their quality of life.

For Padowski and her team, the work is far from over.

The research group has a new batch of volunteers who are completing a longer-term study. Study participants self-administer nasal glutathione three times daily, and undergo MR spectroscopy before and after three months of glutathione therapy. These measurements will allow the research team to compare changes in glutathione levels with reported symptoms.

Other central nervous system disorders for which glutathione deficiency and glutathione-related enzyme deficits have been documented include multiple sclerosis, autism, Alzheimer’s disease, schizophrenia, and bipolar disease. Further studies will be required to evaluate if glutathione augmentation could be a beneficial therapeutic or neuroprotective approach for these conditions as well.

Research at the WSU College of Pharmacy supports the university’s land-grant mission to address some of society’s most complex issues, specifically WSU’s efforts surrounding developing practical solutions to challenging problems in health care delivery, health care access and disease prevention.

[July 1, 2016] By: Lori J. Maricle