Updates in therapeutics for Parkinsons disease

This summary is based on a webinar with Dr Gaurav Chattree, a movement disorder specialist at Stanford. He walked through what is truly new in Parkinson’s disease care, what is in the research pipeline, and what already helps in daily life. His headline was simple and important. Right now the only intervention with evidence of slowing the disease is exercise. Everything else you will read below is either for symptoms or still being tested. Dr Chattree splits treatments into two groups. Disease modifying therapies aim to slow or halt the biology that drives Parkinson’s. Symptomatic therapies aim to improve how you feel and function without changing the long term course. Both matter. One buys time, the other improves the time you have. A major target for disease modification is alpha synuclein, the protein that clumps in Parkinson’s. The idea is to stop misfolding, block spread, or help the brain clear these clumps. The furthest along is prasinezumab, an antibody that latches on to alpha synuclein. Early trials did not hit their main goals, but longer follow up and digital movement measures suggested slower decline in treated people. On the back of those signals a large phase 3 study is now starting. Other approaches are in play. One company is testing an antibody that crosses into the brain more efficiently using a Trojan horse style shuttle. A vaccine strategy that encourages your own immune system to make alpha synuclein antibodies showed promising antibody responses in mid stage data, with full results to come. Ambroxol, better known as an over the counter cough medicine in some countries, is being repurposed. It appears to boost the activity of a waste clearing enzyme called glucocerebrosidase, which is relevant because faults in that pathway raise Parkinson’s risk. A large phase 3 trial has begun and will track people for two years. Importantly the doses used in trials are far higher than shop bought syrups, so this is not one to self medicate. There is active work on LRRK2, a gene that can over fire in some people with Parkinson’s. Tablets that dial down LRRK2 activity are in phase 2, including studies that also enrol people without the mutation in case the pathway is broadly relevant. Anti inflammatory strategies are another theme. Several drugs that calm brain inflammation have cleared early safety tests and are moving into larger trials to see if function declines more slowly on treatment. Gene therapy has re entered the picture. The Regenerate PD study delivers a protective gene to a movement hub deep in the brain using a modified virus. The virus acts as a delivery van, dropping the gene into cells at the injection site and going no further. This is real brain surgery and the trial includes a sham arm so that only some participants receive the gene. The hope is to make dopamine cells more resilient. We have approvals for similar gene therapies in other conditions, so the platform is credible even if past Parkinson’s attempts have been mixed. Not everything pans out. A large phase 3 trial of exenatide, a drug from the GLP 1 family used in diabetes, did not show benefit despite earlier hints. That does not close the door on metabolism as a target, but it lowers expectations for that class. Another agent, buntanetap, has given unclear signals and appears to be moving focus away from Parkinson’s. On the symptomatic side there is real movement. Two continuous under the skin infusions are now available in some regions. One delivers a levodopa and carbidopa formulation. The other delivers apomorphine, which stimulates dopamine receptors. The aim is steadier control through the day with fewer peaks and dips. People wear a small pump connected to a patch. It can be effective for those with big swings or troublesome dyskinesia, though site care and daily set up are part of the deal. New oral drugs are also on the way. A once daily tablet that works on dopamine pathways in a different way to current options has positive phase 3 results and is under regulatory review. Another tablet that rebalances signalling in the motor circuits of the brain is in phase 3 after encouraging phase 2 data, and a separate medicine for levodopa induced dyskinesia reduced involuntary movements in phase 2 with drowsiness as the main side effect. If confirmed, these will widen the toolkit so care teams can match drugs to the person in front of them. Beyond tablets and pumps, procedures continue to evolve. Focused ultrasound uses converging sound waves to heat and destroy tiny targets in the deep brain that drive tremor, stiffness or dyskinesia. There is no implant, which some people prefer, but the change is permanent and fine tuning later is limited. Deep brain stimulation remains the most flexible surgical option and now includes adaptive systems that read brain signals and adjust stimulation in real time. Researchers are also testing stimulation of the nucleus basalis of Meynert, a region linked to thinking, to see if it may help cognitive symptoms in Parkinson’s. Stem cell therapy is back in controlled trials. The goal here is symptomatic. By placing new dopamine producing cells into movement circuits, the hope is to improve motor function. Early studies saw mixed results and sometimes too much dopamine activity. Newer trials use improved cell lines and delivery, including one off the shelf product now in phase 3 and another that turns a person’s own skin cells into dopamine neurons to reduce rejection. These are still experimental and do not stop the disease process, but they may offer another option in future for movement symptoms. Across all of this Dr Chattree kept pulling us back to what we can use today. Exercise is medicine. Aim for at least 30 minutes, three times a week, hard enough to raise heart rate and breathing. Good sleep, blood pressure control and an active life also help people live better with Parkinson’s. For those interested in trials, university centres, national Parkinson’s charities and ClinicalTrials.gov are the best places to check eligibility and locations. It is easy to feel pulled between hope and hype. The honest state of play is this. There is no approved drug yet that slows Parkinson’s. Several lines of attack have enough momentum to warrant large trials, especially the alpha synuclein approaches and ambroxol. Symptomatic care is improving with smarter pills, continuous infusions, and better brain targeting. If you remember only one line, make it the one Dr Chattree started with. Exercise remains the only proven disease modifier we have today, while the research world works hard to change that.