Parkinson's disease (PD) is the second most common neurodegenerative disorder after [Alzheimer's disease](/diseases/alzheimers-disease), affecting approximately 10 million people worldwide. Clinical trials for PD span a wide spectrum from disease-modifying therapies targeting alpha-synuclein and [LRRK2](/entities/lrrk2) to symptomatic treatments addressing motor and non-motor symptoms. This page provides a comprehensive overview of active and recent clinical trials, organized by mechanism and phase of development. Understanding the trial landscape is essential for researchers, clinicians, patients, and caregivers seeking to stay informed about emerging treatments. [@kalia2015]
Disease-modifying therapies aim to slow or halt the progression of Parkinson's disease rather than merely treating symptoms. The main targets under investigation include alpha-synuclein aggregation, LRRK2 kinase activity, and glucocerebrosidase (GBA) function. These approaches represent the most promising avenues for changing the trajectory of PD, as current treatments only address symptoms and become less effective over time. [@poewe2017]
Alpha-synuclein is a small protein that forms Lewy bodies in PD brains. The hypothesis that alpha-synuclein aggregation drives neurodegeneration has led to multiple immunotherapy approaches. Both active vaccines and passive antibody treatments are in development, aiming to reduce or prevent the formation of toxic aggregates.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after [Alzheimer's disease](/diseases/alzheimers-disease), affecting approximately 10 million people worldwide. Clinical trials for PD span a wide spectrum from disease-modifying therapies targeting alpha-synuclein and [LRRK2](/entities/lrrk2) to symptomatic treatments addressing motor and non-motor symptoms. This page provides a comprehensive overview of active and recent clinical trials, organized by mechanism and phase of development. Understanding the trial landscape is essential for researchers, clinicians, patients, and caregivers seeking to stay informed about emerging treatments. [@kalia2015]
Disease-modifying therapies aim to slow or halt the progression of Parkinson's disease rather than merely treating symptoms. The main targets under investigation include alpha-synuclein aggregation, LRRK2 kinase activity, and glucocerebrosidase (GBA) function. These approaches represent the most promising avenues for changing the trajectory of PD, as current treatments only address symptoms and become less effective over time. [@poewe2017]
Alpha-synuclein is a small protein that forms Lewy bodies in PD brains. The hypothesis that alpha-synuclein aggregation drives neurodegeneration has led to multiple immunotherapy approaches. Both active vaccines and passive antibody treatments are in development, aiming to reduce or prevent the formation of toxic aggregates.
| Drug | Company | Mechanism | Phase | Status |
|------|---------|-----------|-------|--------|
| Prasinezumab | Roche/Genentech | Anti-α-Syn Antibody | Phase 2 | Active |
| Cinpanemab | Biogen | Anti-α-Syn Antibody | Phase 2 | Completed |
Prasinezumab (PRX002) is a monoclonal antibody designed to bind aggregated alpha-synuclein and promote its clearance. The PASADENA Phase 2 trial showed signals of efficacy in slowing motor progression, particularly in patients with earlier disease. Cinpanemab (BIIB054) similarly targets alpha-synuclein aggregates but did not meet its primary endpoint in the SPARK trial, though biomarker evidence of target engagement was observed. [@prasinezumab2022]
LRRK2 (leucine-rich repeat kinase 2) is one of the most common genetic causes of PD. Mutations in LRRK2 cause increased kinase activity, leading to neuronal dysfunction. LRRK2 inhibitors represent a precision medicine approach for the approximately 5-10% of PD patients with LRRK2 mutations, though the drugs may also benefit sporadic PD.
| Drug | Company | Mechanism | Phase | Status |
|------|---------|-----------|-------|--------|
| DNL151 | Denali/Biogen | LRRK2 Inhibitor | Phase 1b | Completed |
| BIIB122 | Denali/Biogen | LRRK2 Inhibitor | Phase 2 | Recruiting |
DNL151 (also known as BIIB122) has completed Phase 1b studies showing target engagement and is now advancing to Phase 2 trials. The development of LRRK2 inhibitors represents an important example of genetic insights leading to targeted therapeutic development. [@denali2023]
Motor symptoms including tremor, bradykinesia, rigidity, and postural instability remain the hallmark of PD. Treatment options include dopamine precursors (levodopa), dopamine agonists, MAO-B inhibitors, and COMT inhibitors. Deep brain stimulation provides an important surgical option for patients with motor complications.
| Treatment | Mechanism | Typical Use |
|-----------|-----------|-------------|
| Levodopa/Carbidopa | Dopamine precursor | First-line |
| Pramipexole | D2/D3 agonist | First-line |
| Rasagiline | MAO-B inhibitor | Early/mid disease |
| Deep Brain Stimulation | Neural modulation | Advanced disease |
Non-motor symptoms including cognitive impairment, depression, anxiety, sleep disorders, and autonomic dysfunction significantly impact quality of life. These symptoms are increasingly recognized as important therapeutic targets, as they often precede motor symptoms and can be more disabling than motor issues in advanced disease.
Glucocerebrosidase (GBA) mutations are the most common genetic risk factor for PD, accounting for approximately 5-10% of cases. [GBA](/entities/gba) deficiency leads to lysosomal dysfunction and alpha-synuclein accumulation. Several therapies targeting GBA function are in development.
| Drug | Company | Mechanism | Phase | Status |
|------|---------|-----------|-------|--------|
| Venglustat | Sanofi | GCase Activator | Phase 2 | Completed |
| LTI-03 | Luc Therapeutics | GCase Activator | Phase 1 | Recruiting |
Venglustat (GZ161) is a glucosylceramide synthase inhibitor that reduces substrate accumulation in cells with GBA mutations. Although the primary endpoint was not met, subgroup analyses suggested potential benefit in certain patient populations. [@venglustat2022]
LRRK2-PD represents a distinct genetic subtype with potentially different pathophysiology. Clinical trials increasingly stratify patients by LRRK2 mutation status to assess treatment effects.
Several trials have investigated neuroprotective agents aimed at preserving surviving [neurons](/entities/neurons). These approaches target various pathways including oxidative stress, mitochondrial dysfunction, and neuroinflammation.
| Drug | Company | Mechanism | Phase | Status |
|------|---------|-----------|-------|--------|
| Inosine | University of Pennsylvania | Urate Elevation | Phase 3 | Completed |
| Isradipine | NINDS | Calcium Channel Blocker | Phase 3 | Completed |
| CoQ10 | Parkinson Study Group | Mitochondrial Support | Phase 3 | Completed |
Inosine supplementation to raise urate levels showed promise in early studies but the Phase 3 SURE-PD3 trial did not meet its primary endpoint. Isradipine, a calcium channel blocker, also did not show significant neuroprotection in the STEADY-PD trial. These negative results highlight the challenges of neuroprotection in established disease. [@neuroprotective2023]
Gene therapy offers the potential for long-lasting treatment through viral vector delivery of therapeutic genes. Targets include genes involved in dopamine synthesis and neuroprotection.
| Drug | Company | Mechanism | Phase |
|------|---------|-----------|-------|
| AAV2-GAD | Neurologix | GAD Gene Therapy | Phase 2 |
| AADC | PTC Therapeutics | AADC Gene Therapy | Phase 1 |
AAV2-GAD delivers the glutamic acid decarboxylase gene to the subthalamic nucleus, increasing GABA production and modulating abnormal neural activity. Results have shown improvement in motor symptoms, though the approach remains experimental. [@aavgad2021]
Detailed pages for specific clinical trials: