Exploring the Possibility of Disease-Modifying Therapies

Research aimed at exploring therapies that could possibly change the course of Parkinson’s disease. For now, Parkinson’s disease treatments focus on managing symptoms—like movement problems, sleep disruption, and fatigue. These therapies help people live better, but they don’t slow the disease itself. The underlying brain cells keep dying, and the disease continues to progress. But here’s the exciting bit: researchers are getting closer to something that could change the game entirely—disease-modifying therapies (DMTs). These aren’t just about managing symptoms—they’re about changing the course of the disease. In a recent Parkinson’s Foundation webinar, Dr. Lorraine Kalia, a neurologist and researcher from Toronto, walked us through what DMTs are, how close we are to finding them, and what research looks most promising right now. 🧠 What Is a Disease-Modifying Therapy? A DMT is a treatment that goes deeper than symptom control. It targets what’s actually causing the disease—in this case, the death of brain cells—and tries to slow it down or stop it. Think of it this way: Symptom treatments (like levodopa) = covering up symptoms, like putting a plaster on a cut. Disease-modifying therapies = stopping the cut from happening in the first place—or at least making it much smaller. Right now, there are no DMTs for Parkinson’s. But research is moving fast, and several promising therapies are in trials. 🧬 What’s Going Wrong in the Brain? Parkinson’s happens when specific brain cells—especially those that produce dopamine—start dying faster than normal. What causes this? It’s a mix of factors, but researchers have zoomed in on a few key troublemakers: Alpha-synuclein: a brain protein that clumps together into harmful blobs. GBA1 gene: when faulty, it disrupts how brain cells clean up waste. LRRK2 gene: when overactive, it causes brain cell chaos. These are the hot topics in research because they don’t just appear alongside PD—they may actually help cause it. So, if we can target these early troublemakers, we might be able to slow or stop the disease. 🔬 What Treatments Are in the Pipeline? Dr. Kalia highlighted three of the most promising areas researchers are focusing on right now: 1. Alpha-Synuclein: The Sticky Protein That Causes Trouble Alpha-synuclein is a normal brain protein—but in Parkinson’s, it misbehaves. It sticks together, forms clumps, and creates Lewy bodies, which damage brain cells. Scientists are trying to: Stop the clumping Break up the clumps Prevent alpha-synuclein from spreading between cells Examples of treatments in development: Prasinezumab: an antibody that “mops up” rogue alpha-synuclein outside cells. BIIB054 and cinpanemab: similar antibody-based treatments. MEDI1341: aims to prevent alpha-synuclein from misfolding in the first place. 👉 One therapy, minzasolmine, didn’t work in trials—but researchers learned from it and are improving the next round of drugs. 2. GBA1 / Glucocerebrosidase: The Cell's Clean-Up Crew The GBA1 gene tells your body how to make an enzyme called glucocerebrosidase (GCase). This enzyme helps brain cells clear away waste—including alpha-synuclein. If GBA1 is faulty, GCase doesn’t work properly. Waste piles up, brain cells get overwhelmed, and they die. Treatments in development: Ambroxol: a common cough syrup ingredient that might boost GCase function. Gene therapy: using a virus to deliver a working copy of the GBA1 gene directly to the brain. Small molecule drugs: designed to help GCase fold properly and do its job better. Some of these treatments are already in phase 2 and 3 clinical trials, meaning they’re being tested in real people to see if they’re safe and effective. 3. LRRK2: The Overactive Troublemaker LRRK2 is a gene that acts like a control panel in brain cells. In some people with Parkinson’s, it goes into overdrive and causes all sorts of problems—including inflammation and disrupted cell function. Interestingly, even people without a LRRK2 mutation may have overactive LRRK2 due to environmental triggers like pesticides. Treatments being studied: LRRK2 inhibitors: calm the gene down and reduce the damage. ASOs (antisense oligonucleotides): these are like gene “off switches” that tell cells to make less LRRK2 protein. Both approaches are already being tested in early human trials. 🧭 Challenges Ahead: Drug Delivery and Biomarkers Two big obstacles are still slowing things down: 🚧 1. Getting Drugs Into the Brain The blood-brain barrier is like airport security for your brain. It protects you from harmful stuff—but it also blocks helpful drugs. To get around this, researchers are: Using spinal injections to deliver drugs directly to brain fluid. Testing focused ultrasound with tiny bubbles to briefly open the barrier and let drugs in. One of Dr. Kalia’s own studies is testing whether this method can deliver GCase to the brain in people with GBA1 mutations. 🧪 2. Tracking Progress with Biomarkers To know if a DMT is working, we need biomarkers—measurable signs of what’s happening inside the brain. We now have: A test for alpha-synuclein clumps in brain fluid—huge progress! Genetic testing through the PD Generation programme to find out if someone has a GBA1 or LRRK2 mutation. More biomarkers are coming soon, including ones to measure enzyme activity. These tools will help match people to the right trials—and one day, the right treatments. 🔍 Want to Join a Clinical Trial? If you’re interested in being part of the future of Parkinson’s treatment: Visit the Michael J. Fox Foundation’s Trial Finder Ask your neurologist or care team Stay updated through PD Buddy (we’ll soon launch a “Join Trials” map feature!) Just remember: not every trial is available in every region, and not every person is eligible. But being informed puts you in the best position to get involved if you choose to. 🧘‍♀️ And What About Inflammation and Stress? Dr. Kalia also touched on inflammation—which is getting more attention in PD research—and stress, which many people with PD say makes symptoms worse. She believes stress likely worsens brain inflammation and could accelerate symptoms. More studies are needed, but finding ways to manage stress—through mindfulness, movement, or support groups—may protect your brain as well as your mood.