If you’re building a sports team, you can’t have everyone play the same position. You need offense and defense, athleticism and game knowledge. Coaches look for the unique contributions each player can make on their team.
When it comes to treating and ultimately eliminating Parkinson’s disease (PD), you’ll find a similarly diverse roster of therapeutic approaches. Given the complexity of PD and its varied causes and contributors, Parkinson’s researchers constantly search for different strategies and additional teammates.
The Michael J. Fox Foundation (MJFF) plays the role of head coach, always on the lookout for a new player that could make a valuable contribution.
Here we review different kinds of therapeutic approaches in testing to slow or stop Parkinson’s disease with some examples of each. After all, each offers a unique hope, and together, they represent our best efforts toward curing PD.
Small molecule therapeutics make up nearly 70 percent of therapies in clinical testing, so they’re a natural place to start understanding treatment approaches to PD. You would recognize many small molecule drugs in your own medicine cabinet, like aspirin and Benadryl, but the class accounts for a much wider array of treatments.
“Small molecule” refers to molecules that bind to targets in the body and alter their function or activity level. There are inhibitors (also called antagonists) that block activity and activators (or agonists) that enhance activity. These drugs stand out because they can often be taken orally as a pill or capsule.
- Biogen and Denali are testing a LRRK2 inhibitor (BIIB122/DNL-151) in human studies. This drug reduces activity level of the LRRK2 protein, which is higher in people with PD.
- From biotech Alkahest, AKST4290 blocks a key protein (eotaxin) that has been associated with diseases ranging from Alzheimer’s to Parkinson’s. Blocking the protein helps with inflammation, immune cell recruitment and the growth of new blood vessels, all of which are important factors in battling neurodegeneration.
Another way to block or activate targets is to intervene in their production. Gene therapies target the genes and their messengers that produce proteins and other cell parts. That could mean adding new copies of a broken gene or turning down the volume on an overactive one.
These treatments usually involve an injection into the area around the brain. Sometimes they require help to deliver a gene into a cell; the gene therapy may be packaged in a tool called a viral vector.
- Prevail Therapeutics is testing PR001, a potentially disease-modifying, single-dose gene therapy for people with Parkinson’s disease that have mutations on the GBA gene. Introducing a healthy gene gives instructions for creating an important enzyme that breaks down harmful protein accumulations in the brain.
- Biogen is developing another therapy targeting LRRK2. Its antisense oligonucleotide (BIIB094) links to LRRK2 messenger RNA (mRNA), which delivers instructions for how to make proteins. BIIB094 interferes in that process to reduce production of the LRRK2 protein.
Another therapeutic approach leverages how the body’s own defense system works to protect itself. Immunotherapies harness the power of the immune system against disease targets. There are two categories: passive immunotherapies, such as an antibody developed in a laboratory, and active immunotherapies, like vaccines that stimulate the body to produce its own response.
Scientists can create antibodies in a laboratory with the specific aim of fighting infection, or in the case of Parkinson’s disease, a dangerous protein in the brain. These treatments are given through an infusion into the bloodstream.
- AstraZeneca and partner Takeda are testing the antibody MEDI1341. This therapy and others in this class target alpha-synuclein, a protein that clumps together in PD and other neurodegenerative diseases, like dementia with Lewy bodies. MEDI1341 aims to lower alpha-synuclein levels and prevent more protein clumping in the brain.
- UCB is currently testing an antibody called UCB7853, which flags toxic alpha-synuclein for the body to remove. A Phase I study of the antibody is set to conclude in 2023.
Vaccines take a similar approach but rely on a person’s immune system to produce the antibody, as opposed to delivering it fully formed. Scientists introduce an inactive disease agent that induces the body to mount its own immune response.
- MJFF funded early work around the first vaccine for Parkinson’s in testing from biotech AFFiRiS. After acquiring that company, AC Immune will run a clinical trial on the vaccine, which trains the body how to produce an immune response to alpha-synuclein buildup.
Cell and Tissue Therapies
Cell and tissue therapies work on bolstering or repairing the body’s natural systems. These approaches can replace damaged cells or provide better “growing” conditions for cells to replace themselves.
- MJFF funded early efforts to engineer stem cells into dopamine neurons. Now a company called BlueRock Therapeutics is running a clinical trial implanting the engineered neurons, replacing the natural cells lost in Parkinson’s.
- Foundation-funded researchers at the University of Texas are looking at a cell therapy to ease brain inflammation. Mesenchymal stem cells are derived from a donor’s bone marrow. They can secrete anti-inflammatory molecules and may help create an environment that allows damaged brain cells to regenerate.
You may recognize the name peptide because these short strings of amino acids have uses ranging from anti-aging to musclebuilding. Amino acids are building blocks of proteins. Peptides speak the body’s language, so they may be able to convince the body to make changes that could help combat the effects of disease.
- With MJFF funding, Longevity Biotech is testing the peptide LBT-3627. This therapy hits a receptor in the body, which helps the immune system transform the environment in the brain from one causing damage to one promoting cell growth.
When you look at the “roster” of Parkinson’s disease therapies, you can see the potential. Each player on the team brings something to the field, and together, they can mount a diverse and robust response.
Still, The Michael J. Fox Foundation isn’t done searching for the next answer.
We’re always looking to recruit for our team.
This resource was made possible by Prevail Therapeutics. Partner support allows us to furnish high-quality educational content to the Parkinson’s community while maintaining our commitment to allocate donor dollars to high-impact research. The Michael J. Fox Foundation is solely responsible for the content on this page.