Targeting Parkinson Disease "Pathway Abnormalities" With GT-02287: Jonas Hannestad, MD, PhD

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"We know dopamine works really well, but beyond that, we don't really fully understand how Parkinson works. There are many, what I call 'pathway abnormalities'—things that are different in cells of somebody with Parkinson from somebody who doesn't have Parkinson. Those pathway abnormalities may be things that you can target [with disease-modifying therapies]."

At the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, interim data were presented by Jonas Hannestad, MD, PhD, which detail the open-label, phase 1b findings to-date of a small trial of 21 participants with Parkinson disease (PD) in Australia. The study's primary goal is to determine the therapy's safety and tolerability, but secondarily, it is seeking to assess results from mechanistic biomarker readings to confirm target engagement and efficacy signals.

The therapy, GT-02287, is an investigational small-molecule designed to attempt to act as a disease-modifier for PD. All told, it is showing promising early safety and tolerability results in the ongoing phase 1b trial. Although Hannestad, who is the the chief medical officer at Gain, expressed that the results must be taken with "a grain of salt" as they are early phase and the trial is not powered for efficacy, the positive signals on the MDS Unified Parkinson's Disease Rating Scale Parts I and II do offer some momentum for the treatment's future development.

While on-site at the congress, NeurologyLive spoke with Hannestad further to discuss the results, but also to glean his perspective on the state of therapuetic availability for patients with PD. He offered his thoughts on the current model of therapy, often beginning with dopeminergic targeting treatments—such as the gold standard in PD, levodopa—which offers great symptomatic relief to patients, particularly early on. However, long-term, these approaches have some limitations, with patients experiencing wearing off effects and lessened efficacy. Additionally, he noted, these treatments do not offer disease-modifying effects—simply put, they do not slow disease progression. Many therapies in the pipeline are being evaluated for their ability to potentially do this, and Hannestad provided some context on the targets that GT-02287 acts on in its attempt to modify disease progression in PD.

Click here to read more from MDS 2025.

REFERENCES
1. Pozzi R, Ignoni T, Bosetti M, et al. GT-02287 in Parkinson’s Disease: Interim Data from a Phase 1b Study. Presented at: International Congress of Parkinson’s Disease and Movement Disorders; October 5-9, 2025; Honolulu, HI.