The GLP1 weight loss drugs offering new hope for Parkinson’s treatment

Beyond diabetes: Exploring lixisenatide’s neuroprotective effects; some thoughts on why evolution has not finely tuned our GLP 1 system

Longtime readers of this newsletter will know I have been paying close attention to the new GLP-1 weight loss drugs which seem to positively affect all sorts of conditions far beyond overweight. I've been especially interested in their effects in the brain, where it appears they may have very profound effects on a wide variety of brain systems beyond those involved in the control of appetite - they seem to positively affect anxiety, substance use disorders, cravings, brain plasticity, and a whole lot more. I remain convinced there is a medical revolution in prospect offered by these drugs - the broad spectrum of positive effects of various of these drugs is remarkable. I've summarised many of these findings in the following pieces:

• Altered states: Navigating the hunger game (Part one) - Semaglutide's role in appetite regulation

• Altered States: Rewiring cravings (Part two) - Semaglutide's potential impact on substance use disorders and brain plasticity

• Altered States: transformative potential of the new weight-loss drugs - twenty-two empirical predictions (part three) - The new weight-loss drugs have the potential to be personally, socially, and economically transformative

• A new medication effective for weight loss

Along comes another amazing finding - slowing the progression of Parkinson’s disease

Parkinson's disease is a neurodegenerative disorder characterised by motor symptoms such as tremors, rigidity, and slow movements, and it is a very significant public health concern.

From wiki:

As of 2024, Parkinson's is the second most common neurodegenerative disease and the fastest-growing in total number of cases. As of 2023, global prevalence was estimated to be 1.51 per 1000. Although it is around 40% more common in men, age is the dominant predeterminant of Parkinson's. Consequently, as global life expectancy has increased, Parkinson's disease prevalence has also risen, with an estimated increase in cases by 74% from 1990 to 2016. The total number is predicted to rise to over 12 million patients by 2040.

Parkinson’s disease was first formally described in 1817 by the English physician, James Parkinson, in “An Essay on the Shaking Palsy (Paralysis Agitans)”, who described describing it as involving:

‘Involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured.’

Despite some advances in treatment, there remains a pressing need for novel therapeutic approaches that can effectively slow the progression of the disease.

William Gowers; retouched by User:Dustfreeworld, Public domain, via Wikimedia Commons

Here, I examine the exciting potential of lixisenatide (a glucagon-like peptide-1 (GLP-1) drug as a potential treatment for Parkinson's disease. This medication, originally developed for diabetes, has shown unexpectedly promising results at slowing the progression of Parkinson’s disease in a recent study.

I also recommend reading my previous pieces on metabolism and on exercise:

• Burn, baby, burn: Metabolism Matters - Eating, Exercise, and Evolution Impact Our Energy Burn

• 'Eat less, exercise more' is useless advice; Our activity levels are up -'Toy models' of metabolism and exercise don't work... Something else is going on...

• Too hot to handle: Thermal strain - are you cool-headed or warm-hearted?

• Hypersleep in Aliens, torpor in animals: Slowing your metabolism, energy conservation, and other metabolic marvels

• In Praise of Walking: Chapter 2

The Role of GLP-1 Drugs in Parkinson's Disease

A recent phase 2 trial published in the New England Journal of Medicine investigated participants with and early-stage Parkinson's disease treated with lixisenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, more usually used to treat type 2 diabetes.

👋 Here in the BrainPizza Newsletter, I take a fresh look at life through an informed, empirical, neuroscience and psychology lens. I do regular in-depth treatments of topics such as our very human metabolism, George Orwell, AI hype, brain implants, memory, hunger, NIMBYism, thinking, how to write books, and much, much more, as well as occasional listicles, readings, book reviews, and commentaries. You can browse the archives here; if you’d like to get these regular in-depth emails in your inbox, you can subscribe here.

Understanding Phase 2 Trials

Phase 2 trials are a critical step in the development of new drugs. These trials typically involve many tens to perhaps at most a few hundred participants, and are designed to assess both the efficacy and safety of a drug after its initial safety has been confirmed in Phase 1 trials. Unlike the larger-scale Phase 3 trials, which often involve thousands of participants across multiple locations, Phase 2 trials are smaller and more focused.

The results of this trial were very striking and unexpected. Although Phase 2 trials are not definitive and don't involve the large-scale randomization and controls seen in Phase 3 trials, the findings from this study are quite remarkable and largely unexpected.