<div class="infobox infobox-institution">
{| class="infobox-table"
| colspan="2" class="infobox-header" | Linked Clinical Trials (LCT) Program
|-
| Established | 2009
|-
| Lead Organization | [Cure Parkinson's](/institutions/cure-parkinsons)
|-
| Type | International Clinical Trials Consortium
|-
| Focus | Accelerating disease-modifying therapies for [Parkinson's disease](/diseases/parkinsons-disease)
|-
| Website | [linkedclinicaltrials.org](https://www.linkedclinicaltrials.org)
|}
</div>
Linked Clinical Trials (LCT) is the flagship international clinical trials program of [Cure Parkinson's](/institutions/cure-parkinsons), a UK-based charity dedicated to finding a cure for [Parkinson's disease](/diseases/parkinsons-disease). Founded in 2009, LCT represents a unique approach to drug repurposing, bringing together leading [Parkinson's disease](/diseases/parkinsons-disease) researchers, pharmaceutical companies, and people with [Parkinson's disease](/diseases/parkinsons-disease) to rapidly advance promising disease-modifying therapies through clinical trials.
The program has reviewed over 200 compounds and has been instrumental in advancing more than 30 repurposed drugs into clinical trials for [Parkinson's disease](/diseases/parkinsons-disease), making it one of the most productive drug repurposing initiatives in the [Parkinson's disease](/diseases/parkinsons-disease) field.
<div class="infobox infobox-institution">
{| class="infobox-table"
| colspan="2" class="infobox-header" | Linked Clinical Trials (LCT) Program
|-
| Established | 2009
|-
| Lead Organization | [Cure Parkinson's](/institutions/cure-parkinsons)
|-
| Type | International Clinical Trials Consortium
|-
| Focus | Accelerating disease-modifying therapies for [Parkinson's disease](/diseases/parkinsons-disease)
|-
| Website | [linkedclinicaltrials.org](https://www.linkedclinicaltrials.org)
|}
</div>
Linked Clinical Trials (LCT) is the flagship international clinical trials program of [Cure Parkinson's](/institutions/cure-parkinsons), a UK-based charity dedicated to finding a cure for [Parkinson's disease](/diseases/parkinsons-disease). Founded in 2009, LCT represents a unique approach to drug repurposing, bringing together leading [Parkinson's disease](/diseases/parkinsons-disease) researchers, pharmaceutical companies, and people with [Parkinson's disease](/diseases/parkinsons-disease) to rapidly advance promising disease-modifying therapies through clinical trials.
The program has reviewed over 200 compounds and has been instrumental in advancing more than 30 repurposed drugs into clinical trials for [Parkinson's disease](/diseases/parkinsons-disease), making it one of the most productive drug repurposing initiatives in the [Parkinson's disease](/diseases/parkinsons-disease) field.
The LCT is governed by an international committee of leading [Parkinson's disease](/diseases/parkinsons-disease) researchers who evaluate compounds based on:
| Evaluation Criterion | Weight |
|---------------------|--------|
| Scientific Rationale | High |
| Preclinical Evidence | High |
| Safety Profile | High |
| Feasibility | Medium |
| Patient Accessibility | Medium |
The committee meets annually to review new compounds based on:
Selected compounds advance to clinical trial planning:
| Stage | Description |
|-------|-------------|
| Protocol Development | Customized trial design for [Parkinson's disease](/diseases/parkinsons-disease) |
| Regulatory Submission | CTA/IND applications |
| Site Selection | International trial centers |
| Patient Recruitment | Partnership with patient organizations |
Multi-site, international clinical trials:
| Drug | Original Indication | PD Target | Trial Phase |
|------|---------------------|-----------|--------------|
| [Exenatide](/therapeutics/exenatide-parkinsons-disease) | Diabetes | [GLP-1R](/proteins/glp-1-receptor) | Phase III |
| [Ambroxol](/therapeutics/ambroxol-parkinsons) | Mucolytic | [GBA](/genes/gba) | Phase II |
| Inosine | Gout | Urate elevation | Phase III |
| [Nilotinib](/therapeutics/nilotinib-parkinsons) | Leukemia | [Autophagy](/mechanisms/autophagy) | Phase II |
| Simvastatin | High cholesterol | Neuroprotection | Phase II |
| Metformin | Diabetes | AMPK | Phase II |
| Drug | Trial Phase | Outcome |
|------|-------------|---------|
| Exenatide | Phase II | Positive motor outcomes |
| Ambroxol | Phase II | Safe, GBA activity increased |
| Inosine | Phase II | Urate raised safely |
| Rasagiline | Phase III | Mixed results |
| Metric | Value |
|--------|-------|
| Compounds Reviewed | 200+ |
| Trials Initiated | 30+ |
| Countries Involved | 15+ |
| Patients Enrolled | 5,000+ |
| Funding Raised | £50M+ |
The LCT program is funded through:
Exenatide represents the most advanced therapeutic candidate in the LCT pipeline[@ayers2020]. Originally developed for type 2 diabetes, exenatide is a GLP-1 receptor agonist that has shown neuroprotective properties in preclinical models of Parkinson's disease.
Mechanism of Action:
GLP-1 receptors are expressed in the brain, including in dopaminergic neurons. Activation of these receptors promotes neuronal survival, reduces neuroinflammation, and enhances mitochondrial function. In Parkinson's disease models, exenatide treatment protects dopaminergic neurons from toxin-induced degeneration and improves motor function.
Clinical Development:
The Phase II trial demonstrated that exenatide treatment resulted in significant improvements in motor scores compared to placebo[@exenatide]. These results represented the first positive Phase II trial of a GLP-1 agonist in Parkinson's disease and paved the way for the ongoing Phase III trial. The Phase III trial is evaluating whether exenatide can slow disease progression in patients with early-to-mid stage Parkinson's disease.
Current Status:
The Phase III trial is enrolling patients across multiple international sites. Primary endpoints include change in motor scores and safety assessments. Secondary endpoints include biomarker measurements and non-motor symptom assessments.
Ambroxol represents a targeted therapy approach for Parkinson's disease patients with GBA mutations[@mulhall2020]. GBA mutations are among the most common genetic risk factors for Parkinson's disease, and impair the function of glucocerebrosidase, a lysosomal enzyme.
Mechanism of Action:
Ambroxol acts as a pharmacological chaperone that increases GBA enzyme activity. By restoring GBA function, ambroxol reduces accumulation of glucosylceramide, which may contribute to alpha-synuclein aggregation. This represents a disease-modifying approach targeting the underlying genetic cause in GBA-PD patients.
Clinical Development:
Phase II trials demonstrated that ambroxol safely increased GBA enzyme activity in cerebrospinal fluid[@ambroxol]. The treatment was well-tolerated with no significant adverse events. These results support advancement to Phase II/III trials that will evaluate whether ambroxol can slow disease progression in GBA-PD patients.
Current Status:
Phase II/III trials are evaluating ambroxol in patients with Parkinson's disease who carry GBA mutations. These trials include biomarker assessments to confirm target engagement and clinical endpoints to evaluate efficacy.
Elevated serum urate has been associated with reduced Parkinson's disease risk in epidemiological studies. The LCT program has advanced inosine as a strategy to raise urate levels in Parkinson's disease patients[@scherer2020].
Mechanism of Action:
Urate is a natural antioxidant that may protect dopaminergic neurons from oxidative damage. Higher urate levels correlate with slower disease progression in Parkinson's disease. Inosine supplementation raises serum urate levels, potentially providing neuroprotection.
Clinical Development:
The SPRING trial demonstrated that inosine safely raises serum urate levels in Parkinson's disease patients. Target engagement was confirmed through measurement of urate in cerebrospinal fluid. The Phase III trial is evaluating whether urate elevation can slow disease progression.
Current Status:
Phase III trials are ongoing to evaluate the disease-modifying potential of inosine in Parkinson's disease. Patients are being monitored for both efficacy and safety endpoints.
Nilotinib, originally developed for chronic myeloid leukemia, has been repurposed for Parkinson's disease based on its ability to activate autophagy[@paolone2019].
Mechanism of Action:
Nilotinib inhibits ABL tyrosine kinase, which activates the autophagy pathway. Enhanced autophagy may help clear toxic protein aggregates, including alpha-synuclein. This represents a novel approach to promoting protein clearance in Parkinson's disease.
Clinical Development:
Phase II trials demonstrated that nilotinib is safe in Parkinson's disease patients and shows evidence of autophagy pathway activation. The drug penetrates the blood-brain barrier at concentrations that inhibit ABL. Phase IIb trials are planned to evaluate efficacy.
Current Status:
Phase IIb trials are being designed to evaluate whether nilotinib can provide disease-modifying benefits in Parkinson's disease.
Simvastatin:
Simvastatin, a cholesterol-lowering drug, has neuroprotective properties that may benefit Parkinson's disease patients[@chaturvedi2021]. The LCT has advanced simvastatin to Phase II trials evaluating its disease-modifying potential.
Metformin:
Metformin activates AMPK, a cellular energy sensor that promotes metabolic health and may provide neuroprotection[@meissner2021]. Phase II trials are evaluating metformin in Parkinson's disease.
The LCT continuously evaluates new compounds for the drug repurposing pipeline. Several candidates are in various stages of preclinical and early clinical development:
Neurotrophic Factors:
GDNF and related neurotrophic factors have shown promise in preclinical models of Parkinson's disease. These proteins promote the survival and function of dopaminergic neurons. The LCT has supported early-stage clinical work on neurotrophic factor delivery approaches.
Antioxidants:
Given the role of oxidative stress in Parkinson's disease pathogenesis, antioxidants represent another therapeutic strategy. Coenzyme Q10 and other compounds have been evaluated in clinical trials supported by the LCT program.
Anti-inflammatory Agents:
Chronic neuroinflammation contributes to Parkinson's disease progression. The LCT has evaluated anti-inflammatory agents that may modulate microglial activation and reduce neuroinflammation.
Future directions include combination therapy approaches that target multiple pathological pathways simultaneously:
The LCT program has significantly accelerated the drug repurposing pipeline for Parkinson's disease. By providing a systematic approach to evaluating existing drugs, the program has moved more than 30 compounds into clinical trials that would not otherwise have been tested in Parkinson's disease.
The program has established infrastructure that benefits the entire Parkinson's disease research community:
The LCT has influenced research priorities in the Parkinson's disease field by highlighting the importance of drug repurposing and disease modification. This has led to increased funding and interest in these areas.
LCT research has been highly influential, with numerous publications in high-impact journals. The program's work on Exenatide, Ambroxol, and other candidates has been cited extensively in the scientific literature.
LCT investigators regularly present their findings at major conferences including:
The LCT supports training the next generation of Parkinson's disease researchers through:
The LCT maintains sustainability through diverse funding sources:
Charitable Funding:
Cure Parkinson's provides core funding that supports program operations. Individual donors and charitable foundations contribute to the program's activities.
Industry Partnerships:
Pharmaceutical company partnerships provide both funding and in-kind support for clinical trials. These partnerships are structured to ensure scientific independence.
Research Grants:
Competitive research grants from government and charitable sources support specific research projects and clinical trials.
The LCT develops strategic plans that guide program priorities:
The Linked Clinical Trials program represents a unique and successful approach to accelerating disease-modifying therapies for Parkinson's disease. Through systematic evaluation of existing drugs, rigorous clinical trial design, and strong international collaboration, the program has advanced more than 30 compounds into clinical testing. The Exenatide Phase III trial and other ongoing studies represent the culmination of years of effort to bring disease-modifying therapies to Parkinson's disease patients. As the program continues to evaluate new candidates and advance the current pipeline, it remains a central pillar in the effort to find effective treatments for Parkinson's disease.
The LCT international committee follows a rigorous process for evaluating potential therapeutic candidates:
Annual Review Meeting:
The committee meets annually to review new compounds and evaluate the progress of ongoing trials. This meeting brings together leading Parkinson's disease researchers, patient representatives, and industry partners.
Evaluation Criteria:
Compounds are evaluated based on scientific rationale, preclinical evidence, safety profile, feasibility, and patient accessibility[@bjorklund2022]. Only compounds with strong evidence supporting their potential benefit are advanced to clinical trials.
The committee includes leading Parkinson's disease researchers from around the world:
The LCT program has pioneered innovative clinical trial designs for Parkinson's disease[@vancamp2022]:
Motor Endpoints:
Phase IIa:
Proof-of-concept trials typically enroll 50-100 patients and run for 6-12 months. These trials evaluate safety and preliminary efficacy signals.
Phase IIb:
Dose-finding and efficacy trials enroll 100-200 patients and run for 12-24 months. These trials establish optimal dosing and gather efficacy data to support Phase III trials.
Phase III:
Confirmatory trials enroll 300-500 patients and run for 24-36 months. These trials provide the definitive evidence needed for regulatory approval.
The LCT program includes a Patient Advisory Board that provides input on trial design, recruitment strategies, and research priorities. This ensures that patient perspectives are incorporated into all aspects of the program.
LCT works with patient organizations to support recruitment for clinical trials:
Patient-reported outcomes are incorporated into clinical trials to capture the full impact of treatments on quality of life[@deer2021].
LCT research has been published in leading journals and presented at major conferences:
LCT collaborates with international research networks:
The LCT program continues to evaluate new therapeutic candidates:
LCT is developing approaches to target therapy based on patient genetics:
Continued biomarker development will enable: