Promising New Treatments for Parkinson’s: What’s in the Clinical Trial Pipeline?
There remains an urgent unmet need for Parkinson’s disease (PD) treatments that slow or halt the underlying neurodegenerative process that leads to disease progression. Much research is focused on this, with clinical trials underway.
It is also critical that medications continue to be developed that focus on improving PD symptoms. Many molecules are in clinical trial for this purpose as well.
Below we will review five exciting compounds that are currently making their way through the PD pipeline. You may also want to review past blogs that describe both neuroprotective and symptomatic strategies that are in clinical trial:
- Future Parkinson’s disease treatments in clinical trial
- Therapies for non-motor symptoms in clinical trials
- Repurposed medications being studied for PD
- Medications in clinical trials – 2023
- Parkinson’s disease medication pipeline
- Alpha-synuclein strategies for Parkinson’s disease
Five potential medications in the PD research pipeline
1. Ambroxol: A Small-Molecule Chaperone for GCase
Mechanism:
Ambroxol is a cough suppressant repurposed as a molecular chaperone that boosts lysosomal glucocerebrosidase (GCase) activity. A chaperone is a protein that helps another protein function properly. By increasing GCase activity, amboroxol helps to improve clearance of cellular garbage, including α-synuclein aggregates.
Key Trials:
- The GRoningen Early-PD Ambroxol Treatment (GREAT trial) is underway in Europe, testing whether high-dose ambroxol slows motor progression. This trial NCT05830396 is designed to evaluate the efficacy of ambroxol in patients with early-stage PD who carry a GBA gene mutation, a common contributor to PD risk. The primary outcome focusing on changes in motor and non-motor symptoms over a 12-month period.
- Earlier open-label work confirms ambroxol crosses the blood–brain barrier, raises CSF GCase levels, and appears safe at therapeutic doses NCT05287503.
Why It’s Exciting:
Since dysfunction of lysosomes may be a root cause of PD in general, improving the functioning of lysosomes with ambroxol may help everyone with PD, not just those with a GBA mutation.
2. Inzomelid, NT-079, VTX3232, VENT-02, Dapansutrile (OLT1177): Targeting the NLRP3 Inflammasome
Mechanism:
Chronic activation of the NLRP3 inflammasome in microglia drives sustained neuroinflammation, which can accelerate α-synuclein aggregation and neuronal death.
Key Agents & Trials:
- Inzomelid (Emlenoflast formerly from Inflazome/Biohaven): Preclinical data show robust IL-1β suppression; Phase 1 healthy-volunteer studies demonstrated safety and target engagement at ALZForum overview.
- NT-0796 (NodThera): A brain-penetrant NLRP3 inhibitor that just completed a combined Phase 1b/2a in PD patients, showing dose-dependent reductions in blood IL-1β and neuroinflammatory markers in the Company Report.
- VTX3232 (Zomagen Biosciences) is currently being studied in a Phase 2a study. NCT06556173
- VENT-02 (Ventus Therapeutics) is currently being studied in a Phase 1b study. NCT06822517
- Dapansutrile (Olatec Therapeutics) is currently being studied in a Phase 2 trial
Why It’s Exciting:
If chronic neuroinflammation truly fuels disease progression, NLRP3 blockade could offer a wholly new disease-modifying strategy.
3. AAV2-GDNF: Gene Therapy to Deliver Neuroprotective Growth Factor
Mechanism:
AAV2-GDNF is an investigational gene therapy that delivers the gene encoding glial cell line-derived neurotrophic factor (GDNF) directly into an important brain region called the putamen, using an adeno-associated virus serotype 2 (AAV2) vector. GDNF is a naturally occurring protein that supports the survival and function of dopaminergic neurons. By using viral vectors to introduce the GDNF gene into specific brain regions, this therapy aims to stimulate long-term production of GDNF at the site of the degeneration, potentially protecting or even restoring neurons affected by PD.
Key Trials:
- The initial Phase I trial NCT01621581 completed the initial safety and biodistribution of AAV2-GDNF in PD patients undergoing MRI-guided infusion into the putamen area of the brain. The results showed that the surgical delivery approach was safe and well-tolerated with evidence of widespread vector distribution.
- A new Phase 2 Trial NCT06285643 is underway to evaluate the safety, biodistribution, and exploratory efficacy of AAV2-GDNF delivered via convection-enhanced delivery (CED) in patients with moderately advanced PD.
Why It’s Exciting:
Gene therapies like AAV2-GDNF represent a transformative approach to Parkinson’s care potentially enabling continuous, localized, production of therapeutic proteins within the brain. While still early in development, this strategy could provide durable neuroprotection without the need for daily pills or infusions, reshaping how we approach disease modification.
4. Solangepras (CVN-424): Targeting GPCR6 for Motor and Cognitive Enhancement
Mechanism:
Solangepras, also known as CVN-424, is an oral small molecule that acts as an inverse agonist of a protein called the G-protein coupled receptor 6 (GPCR6). GPCR6 is predominantly expressed in the striatum, a brain region integral to motor control. By inhibiting GPCR6, Solangepras changes the striatal signaling pathways, potentially improving both motor and cognitive functions without directly stimulating dopamine receptors.
Key Trials:
- A Phase 2 trial NCT04191577 evaluated Solangepras as an adjunctive treatment to levodopa in Parkinson’s patients experiencing motor fluctuations. The study found that the 150 mg dose of Solangepras significantly reduced daily OFF-time by 1.3 hours compared to placebo.
- Building on these results, a subsequent Phase 3 trial NCT06553027 is underway to assess the efficacy of Solangepras as a stand-alone monotherapy in PD patients with motor fluctuations.
Why It’s Exciting:
By targeting a non-dopaminergic pathway, Solangepras offers a novel approach that may provide symptomatic relief with a reduced risk of side effects commonly associated with traditional dopaminergic therapies.
5. Glovadalen (UCB0022): Enhancing Dopamine D1 Receptor Activity
Mechanism:
Glovadalen is an orally active, brain-penetrating positive allosteric modulator (PAM) of the dopamine D1 receptor. Unlike direct agonist, Glovadalen enhances the receptor’s response to endogenous dopamine, amplifying D1 receptor signaling only in the presence of dopamine. This selective modulation aims to improve motor function while minimizing side effects.
Key Trial:
- The initial Phase I trial NCT04867642 completed the initial safety and tolerability in healthy individuals.
- UCB just completed a Phase 2 Trial NCT06055985 to evaluate the efficacy, safety, tolerability and pharmacokinetics of Glovadalen in participants with advanced PD.
Why It’s Exciting:
By fine-tuning the dopaminergic system, Glovadalen represents a promising strategy to restore motor function with potentially fewer complications than traditional dopamine therapies.
Looking Ahead
These strategies are just a selection of the innovative agents that are being tested for potential neuroprotective effects or symptomatic benefit. We continue to thank Dr. Kevin McFarthing, a biochemist and person with Parkinson’s for his efforts in creating and maintaining The Parkinson’s Hope List — a collation of all the compounds that are being explored as new therapies for PD at all stages of the research pipeline and is updated frequently. It is an excellent source of information for those interested in the current state of PD research focused on new potential treatments.
We will continue to keep you posted with new developments as we watch this exciting era of PD therapeutics unfold.
We extend our thanks to Clark Jones, PhD, for his significant contributions to this blog.
Tips & Takeaways
- There are multiple treatment strategies in the PD research pipeline.
- Potential treatments are generally divided into two large categories: disease modifying therapies and symptomatic treatments.
- In this blog we highlighted five exciting strategies of potential new PD treatment: decreasing neuroinflammation, enhancing lysosomal activity, supporting survival of nerves, enhancing the body’s response to dopamine, and enhancing motor circuitry without stimulating dopamine pathways
- APDA supports essential research, bringing new ideas to fruition in the treatment of PD. Read about what we are currently funding.
- We need your support to continue this extremely valuable research. Click here if you’d like to donate.