In recent developments in Parkinson’s disease research, several investigational therapies are showing potential to change the treatment landscape. Last month, AC Immune announced that its active immunotherapy slowed disease progression in a mid-stage trial, marking a first for this approach in Parkinson’s.
Despite significant investment in Parkinson’s research, experts agree that current treatments remain limited. Pinky Agarwal, professor of neurology at the University of Washington, told BioSpace by email there remains a “strong need” to develop new medicines and explore alternative therapeutic pathways for the neurodegenerative condition. Agarwal explained that most existing therapies focus on supplementing dopamine levels or activating dopamine receptors, but these approaches only temporarily alleviate symptoms without stopping disease progression. “Over time, patients experience motor fluctuations, dyskinesias, and increasing non-motor symptoms that dopaminergic therapies do not adequately address,” Agarwal said.
The shortcomings of current therapies underscore the need for more targeted and personalized approaches. Kelly Mills, director of the Parkinson’s Disease and Movement Disorder Center at Johns Hopkins Medicine, said via email: “I suspect that therapies may need to be targeted for ‘predominant’ mechanisms in individuals.” He noted that some emerging strategies involve modulating immune responses or targeting cellular pathways involved in oxidative stress and mitochondrial dysfunction. “I think [Parkinson’s treatment] will be more personalized at the mechanistic level even when a known risk factor gene is not found,” Mills added.
One company making headlines is Ventyx Therapeutics. The company drew a $1.2 billion buyout bid from Eli Lilly this month for its NLRP3 program, which includes VTX3232—an oral drug in mid-stage development for Parkinson’s disease. VTX3232 inhibits NLRP3 inflammasome activity to reduce inflammation linked to neurodegeneration. Phase II data released last year showed significant reductions in NLRP3 levels and downstream inflammatory markers such as IL-6 and hsCRP.
AC Immune is also pursuing an immune-targeted strategy with ACI-7104.056, designed to stimulate antibody responses against misfolded alpha-synuclein protein—a key driver of neuron loss in Parkinson’s. CEO Andrea Pfeifer told BioSpace by email: “Parkinson’s disease is ‘multisystem and heterogeneous,’ which suggests a need to address the major mechanistic drivers, for disease modification and neuroprotection.” Interim data from AC Immune’s Phase II VacSYn study indicated stabilization of biomarkers related to neuronal damage and trends toward modifying disease course.
Gain Therapeutics is advancing GT-02287, an orally available small molecule aimed at restoring proper folding and function of glucocerebrosidase (GCase), an enzyme whose dysfunction contributes to toxic protein build-up in neurons. CEO Gene Mack described this approach as targeting upstream mechanisms responsible for cellular stress: “Rather than simply trying to boost enzyme activity in the lysosome, GT-02287 stabilizes GCase folding and trafficking throughout the cell.” Recent trial data showed significant reductions in GluSph levels—a marker associated with synuclein accumulation.
Denali Therapeutics and Biogen are collaborating on DNL151 (BIIB122), an oral inhibitor of LRRK2 protein mutations implicated in late-onset Parkinson’s disease. After positive early-stage biomarker results—including robust reductions in Rab10 protein—the partners advanced DNL151 into late-stage clinical trials.
Aspen Neuroscience offers a cell therapy approach with ANPD001—a product made up primarily of dopaminergic neuronal precursor cells derived from each patient—to rebuild neural networks damaged by Parkinson’s. Chief Medical Officer Revati Shreeniwas said: “The objective…is to go ‘beyond one-off symptomatic treatments toward true circuit‑level repair.’” In early studies, direct brain delivery was safe with reported improvements in physician- and patient-reported outcomes.
While some biopharma companies have discontinued programs targeting Alzheimer’s and Parkinson’s diseases recently (https://www.biospace.com/article/7-alzheimer-s-and-parkinson-s-programs-discarded-in-2024/), many others continue investing heavily as they pursue potential multi-billion-dollar markets.
As researchers continue investigating these novel therapies—ranging from immune modulation to cell replacement—experts hope new options will provide better long-term outcomes for people living with Parkinson’s disease.
