Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2023 Update

Abstract

Background: Since 2020, annual reports on the clinical development of new drug-based therapies for the neurodegenerative condition of Parkinson’s disease (PD) have been generated. These reviews have followed the progress of both “symptomatic treatments” (ST – improves/reduces symptoms of the condition) and “disease modifying treatments” (DMT - attempts to delay/slow progression by addressing the underlying biology of PD). Additional efforts have been made to further categorize these experimental treatments based on their mechanisms of action and class of drug. Methods: A dataset of clinical trials for drug therapies in PD was obtained using trial data downloaded from the ClinicalTrials.gov online registry. A breakdown analysis of all the studies that were active as of January 31st, 2023, was conducted. Results: There was a total of 139 clinical trials registered on the ClinicalTrials.gov website as active (with 35 trials newly registered since our last report). Of these trials, 76 (55%) were considered ST and 63 (45%) were designated DMT. Similar to previous years, approximately a third of the studies were in Phase 1 (n = 47; 34%), half (n = 72, 52%) were in Phase 2 and there were 20 (14%) studies in Phase 3. Novel therapies again represented the most dominant group of experimental treatments in this year’s report with 58 (42%) trials testing new agents. Repurposed drugs are present in a third (n = 49, 35%) of trials, with reformulations and new claims representing 19% and 4% of studies, respectively. Conclusions: Our fourth annual review of active clinical trials evaluating ST and DMT therapeutics for PD demonstrates that the drug development pipeline is dynamic and evolving. The slow progress and lack of agents transitioning from Phase 2 to Phase 3 is concerning, but collective efforts by various stakeholders are being made to accelerate the clinical trial process, with the aim of bringing new therapies to the PD community sooner.

Lack of genetic evidence for NLRP3-inflammasome involvement in Parkinson’s disease pathogenesis

“…Studies that are not guided by genetic evidence are more likely to fail 12 . Currently, several phase 1 clinical trials targeting neuroinflammation and particularly NLRP3-inflamassome are being conducted 30 . The discordance between the hypothesis underlying these clinical trials targeting NLRP3 pathway in Parkinson's disease and our findings suggests that efforts to target the NLRP3 inflammasome in Parkinson's disease should be critically evaluated.…”

Predictive Modeling to Uncover Parkinson’s Disease Characteristics That Delay Diagnosis

“…Parkinson's disease (PD) is the fastest-growing neurological disease and the second most common neurodegenerative disease (1). Numerous ongoing clinical trials investigate potentially diseasemodifying treatments for PD aiming to stop or significantly slow neurodegeneration (2). This development outlines the increasing importance of early and accurate diagnosis in PD, as timely interventions will be required to maximize the therapeutic benefits of these emerging treatments.…”

Nanophytomedicines as Therapeutic Agents for Parkinson’s Disease

“…As of 2023, there are 139 clinical trials of new drug therapies for PD . Among these, 47 of these trials are in phase I, 70 are in phase II, and 20 are in phase III .…”

“…As of 2023, there are 139 clinical trials of new drug therapies for PD . Among these, 47 of these trials are in phase I, 70 are in phase II, and 20 are in phase III . The phase II trials include two botanical-based medications, namely pypoestoxide and WIN-1001X .…”

“…29 Among these, 47 of these trials are in phase I, 70 are in phase II, and 20 are in phase III. 29 The phase II trials include two botanical-based medications, namely pypoestoxide and WIN-1001X. 30 Hypoestoxide is a natural active diterpene phytochemical of Hypoestes rosea that was shown to inhibit the activity of inflammatory pathways and modulate PD features.…”