The Linked Clinical Trials (LCT) Initiative, a repurposing program that aims to identify existing medicines which can slow the progression of Parkinson’s disease, has resulted in a growing number of clinical trials.
The partnership’s history, purpose and activities are the focus of an article, “The Linked Clinical Trials Initiative (LCT) for Parkinson’s disease,” that recently appeared in the European Journal of Neuroscience.
The International Parkinson’s LCT Initiative was conceived in 2010 by Tom Isaacs, late president and co-founder of the London-based Cure Parkinson’s Trust (CPT), and Richard Wyse, the organization’s current director of research and development.
CPT decided to support preclinical and clinical studies of potential disease-modifying therapies (DMTs) and of medications approved for other illnesses in therapy repurposing trials. Symptomatic treatments were not explored, as they were already being extensively investigated in industry-sponsored studies.
The Committee to Identify Neuroprotective Agents for Parkinson’s program greatly influenced the launch of LCT. Initiated in 2003, the program assessed more than 20 potential Parkinson’s therapies. Several were selected to enter clinical trials, but none met their primary clinical goals.
Yet given the ensuing discovery of new disease mechanisms and therapeutic targets, as well as the growing notion that some of the first events in Parkinson’s development occur outside the brain, it seemed “very reasonable to revisit the concept of drug repurposing in [Parkinson’s],” researchers wrote.
LCT’s initial focus was to gain insight from key opinion leaders on appropriate medications to test for potential therapies in Phase 2 trials of Parkinson’s. If successful, these trials would lead to Phase 3 studies and market possible new therapies.
The goal was to have multiple parallel trials comparing different therapies with a similar protocol. Yet the need to for different placebos and durations of treatment, among other factors, made this impossible.
Patrik Brundin, MD, then working at Sweden’s Lund University, agreed to chair the LCT scientific committee. Isaacs and Wyse approached Brundin because of his contributions to the Parkinson’s field and deep understanding of clinical and basic science. Overall, the scientists involved in LCT felt that studies should look at impaired processes — such as neuroinflammation or energy metabolism — and favor compounds able to affect more than one such process.
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Also, as there was no DMT for Parkinson’s, the disease was an attractive target for therapy repurposing, an approach that can be significantly time- and cost effective to find new medications.
The effort included eight scientists, including Brundin. Another scientist, Jeffrey Conn, PhD, of Tennessee’s Vanderbilt University Medical Center, was a global expert in blood-brain barrier penetration and pharmacology. The blood-brain barrier is a semipermeable membrane that protects the brain from the outside environment. Penetrating this barrier and reaching the brain is critical in treating neurological diseases.
Three patients, including Isaacs, attended the first LCT meeting in 2012 at the Van Andel Research Institute in Grand Rapids, Michigan. Also present were representatives from the Michael J. Fox Foundation for Parkinson’s Research, the Parkinson’s Foundation, and Parkinson’s UK. Since then, patient participation has increased, providing immediate access to their perspectives and discussions on trial design and continuation, as well as compliance with specific therapies.
The first LCT meeting led to the launch of six Phase 2 trials. A subset received both LCT committee endorsement and funding from CPT in collaboration with the Van Andel Institute. Meanwhile, four more trials were initiated, two of which — both of the type 2 diabetes medication exenatide (marketed as Byetta/Bydureon) — have led to current plans to launch a Phase 3 study.
Scientists also recently completed a trial (NCT02941822) of the respiratory disease therapy ambroxol, while a study (NCT02462603) on EPI-589 is approaching completion. The authors anticipate that nearly 25 trials will be underway or completed by mid-2019.
“CPT and LCT are delighted that some of the drugs prioritized at LCT annual meetings have not only entered clinical trials under the LCT initiative, but have also now entered independent clinical trials in various centers around the world,” scientists concluded.