U of A lab targets clinical trials for Parkinson’s disease vaccine

A lab in the University of Alberta’s department of biochemistry is considering human clinical trials for its Parkinson’s disease vaccine. Further testing in mice is currently underway to confirm suitability for human trials.

Parkinson’s disease is a neurodegenerative disease that primarily affects movement in patients. Patients may first recognize symptoms such as a tremor in their hands, stiffness, or slowing of movement.

Holger Wille, a professor in the department of biochemistry and director of the Centre for Prions and Protein Folding Diseases (CPPFD), is the lead investigator on this project. Wille’s lab has done extensive work on prion diseases, which involve mechanisms similar to those observed in Parkinson’s disease.

Although Parkinson’s has been linked to specific genetic mutations, the cause in most patients who lack the mutation remains elusive.

“We know that some patients do get Parkinson’s disease because of mutations in one of several specific proteins,” Wille explained. “However, this is at most 10 per cent of cases, meaning in 90 per cent of cases, we don’t fully understand how they arise.”

According to Wille, Parkinson’s disease is also thought to be a result of an accumulation of misfolded proteins. When proteins misfold, they adopt a ‘toxic shape’ different from their normal functional shape. In patients with Parkinson’s, the clearance mechanisms for misfolded proteins are deficient, allowing these proteins to accumulate and lead to the death of neurons.

The Parkinson’s vaccine developed by Wille’s lab mimics the surface of these misfolded proteins based on available structural information. 

“At some point, we could predict the precise surface of these misfolded states and mimic these surfaces in a totally unrelated protein that is safe to work with,” Wille said.

Promising results from vaccine testing in mice

This mimicked protein is the lab’s vaccine candidate for current testing in mice. Preliminary results from the vaccine testing in mice have shown promising outcomes.

Healthy mice that received the Parkinson’s vaccine produced antibodies in response. According to Wille, these antibodies obtained from the mice were able to distinguish between misfolded proteins from Parkinson’s patients and normal proteins from individuals without.

The team also tested the vaccine by inducing Parkinson’s in mice and vaccinating only some of them. 

“The mice that received our vaccine stayed healthy much longer, and survived much longer, up to 40 per cent of their lifespan,” Wille said.

This significant benefit observed in mice has generated interest in clinical trials for the vaccine. Wille expects a time frame of two years before clinical trials might begin in patients with Parkinson’s.

In the meantime, extensive work is being done to prepare for clinical trials. This includes further testing in various strains of lab mice, tests for vaccine safety, and fundraising.

Clinical trial outlook

Regarding the target population of the vaccine, Wille is “thinking of the vaccine as a prophylactic vaccine.” Prophylactic vaccines are given to prevent disease onset or to slow disease progression in patients with early signs.

According to Wille, “this will be given to patients who have shown very early signs, meaning they are on the way to developing Parkinson’s disease.” One common early sign of Parkinson’s disease is REM sleep behaviour disorder, in which individuals physically act out their dreams. The part of the brain that normally prevents motion when dreaming is dysfunctional in early Parkinson’s.

Wille is currently in contact with a clinician working with patients with Parkinson’s who may benefit from this study.

Recognizing that “bringing a vaccine to a market is a major undertaking,” Wille hopes to license it out to a pharmaceutical company if clinical trials succeed. Given the vigorous search for treatments for Parkinson’s, a successful clinical trial would likely draw strong demand.