Drug Repurposing for Parkinson’s Disease: The International Linked Clinical Trials experience

Abstract

The international Linked Clinical Trials (iLCT) program for Parkinson’s to date represents one of the most comprehensive drug repurposing programs focused on one disease. Since initial planning in 2010, it has rapidly grown – giving rise to seven completed, and 15 ongoing, clinical trials of 16 agents each aimed at delivering disease modification in Parkinson’s disease (PD). In this review, we will provide an overview of the history, structure, process, and progress of the program. We will also present some examples of agents that have been selected and prioritized by the program and subsequently evaluated in clinical trials. Our goal with this review is to provide a template that can be considered across other therapeutic areas.

Targeting Macroautophagy as a Therapeutic Opportunity to Treat Parkinson’s Disease

“…A rapid way to implement new therapies is through drug repurposing, which allows previously approved drugs to go directly into phase 2, shortening the length and cost of clinical trials as they already have a safety track record. In the pipeline of drug candidates to treat PD, at least 16 compounds have that characteristic ( Stott et al, 2021 ), including drugs targeting proteins linked to autophagy, such as quetiapine, an antipsychotic that targets GCase ( Burbulla et al, 2021 ). However, drug repurposing can be challenging ( Keerie et al, 2021 ) and the identification of novel autophagy targets [such as ubiquitin ( Schmidt et al, 2021 )] and new drugs targeting this process is of utmost importance to use autophagy as a therapeutic tool in PD ( Stacchiotti and Corsetti, 2020 ; Wang Z.-Y.…”

The Role of Pathogens and Anti-Infective Agents in Parkinson’s Disease, from Etiology to Therapeutic Implications

“…If the role of infection in PD can be confirmed, it will provide a new direction and target for the treatment of PD. Besides, drug repurposing can quickly introduce drugs with well-documented safety to new patient populations, significantly speeding up the drug development process [ 169 ]. Recently, a nationwide case-control study was carried out, suggesting that early overexposure to antibiotics, particularly antianaerobics and broad-spectrum antibiotics, is associated with subsequent PD, with a delay of 10 to 15 years, which is consistent with the proposed duration of a prodromal period [ 170 ].…”

The Unbearable Lightness of Brundin

“…The obvious great advantage here is that the safety and side-effects are already wellestablished, so the process from bench to bedside can be greatly accelerated. The International Linked International Trials initiative has already resulted in seven completed, and 15 ongoing, clinical trials of 16 agents, each aimed to potentially modify the course of Parkinson's disease [3]. Throughout this process, Patrik has acted as a crucial chair of the program -distilling complex discussions, managing diverse viewpoints and allowing for clarity of decision making.…”