Is a vaccine for Parkinson’s disease possible?

As the world awaits an effective vaccine for SARS-CoV2 (the virus that causes COVID-19), vaccines and vaccination are at the front and center of the news and in our minds.
A vaccine is a substance that is introduced into the body in order to stimulate the immune system to provide protection against a particular disease.
Did you know that many pharmaceutical companies are working on vaccinations as a treatment for Parkinson’s disease (PD)?  It is important to note that while a vaccine is not imminent, each clinical trial and study that is underway is teaching us something new and important that will hopefully get us closer to a successful outcome. Even the projects that fail offer us substantial learnings that can be applied to future research efforts in this area.
People with PD have protein deposits in their brain (Lewy bodies) which are composed of accumulated α-synuclein. Preventing alpha-synuclein aggregation and dissolving pre-formed aggregates (or clumps) may be an effective strategy for treating PD.
Two related strategies have been devised in order to protect against this accumulation:

Introduction of antibodies to alpha-synuclein into the body, also known as passive immunity
Introduction of a molecule that induces the body to produce its own antibodies against alpha-synuclein, also known as active immunity

The theory is that in both scenarios, the antibodies to alpha-synuclein (either introduced directly or created by the body) would bind to clumped alpha-synuclein and aid in their removal. Let’s look at these scenarios in more depth.
Alpha-synuclein antibodies (passive immunity)
There are multiple research efforts underway to create and test antibodies against alpha-synuclein.
The prasinezumab antibody
This antibody was studied in a Phase 2 trial called PASADENA, with 316 participants, all with newly diagnosed PD who had mild symptoms and were not on any medication for PD. The trial was double-blinded and placebo controlled which means some people received the drug and some did not, and neither the participants nor the researchers knew which group anyone was in.
This trial has been completed and the data has been analyzed. As happens sometimes in research, it unfortunately did not meet its primary endpoint (the original goal which was stated at the outset as the definition of success of the trial). The primary end point for the trial was an improvement over the course of the year in the total Movement Disorder Society-United Parkinson’s Disease Rating Scale (MDS-UPDRS). This scale has four parts. The first two are filled in by the patient or care partner and assess the motor and non-motor symptoms of PD from the patient’s perspective. The third part is a scale that reflects the motor examination performed by the clinician during the office visit. Part four captures historical and objective information about motor fluctuations and dyskinesias. The trial did not show any difference in the total MDS-UPDRS after one year between those receiving the antibody and those who did not.
It did, however, succeed in meeting some of its secondary endpoints (outcomes that were also determined at the start of the trial, but thought to be of lesser significance than the

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