Welcome to the AD/PD™ 2022 Interactive Program
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PRE-RECORDED: DISEASE MODIFICATION IN PD: WHAT ARE THE PROMISING TARGETS?
Abstract
Abstract Body
Disease modification therapy (DMT) remains the greatest unmet need in PD. Despite a large number of clinical trials conducted over the past 30 years involving thousands of patients and hundreds of millions of dollars, all attempts to define effective DMT have failed. This is despite promising preclinical data, although most earlier studies involved treatments tested in toxin-based animal models that could now be considered of questionable relevance to human Parkinson’s disease. A large number of pathogenic mechanisms and disease modifying functions have been targeted including oxidative stress, mitochondrial dysfunction, excitotoxicity, apoptosis, calcium channel activity, trophic function, and neuroinflammation. More recently, trials of treatments designed to directly target alpha synuclein, specific genetic forms of PD (LRRK2 and GBA) and newer aspects of PD cell biology (e.g. c-Abl kinase, the GLP-1 receptor) have been initiated. Currently, apart from genetic subtypes, we lack specific biomarkers that might define subgroups of patients more likely to benefit from selected treatments (i.e. allowing a precision medicine approach). Typically, past studies have recruited patients with early untreated PD without enriching the study population for patients with a greater chance to benefit from targeting a specific underlying biological process of interest. Thus, one important possible cause for the failure to define effective DMT to date has been the reductionist approach of considering PD as a single disease. In this lecture I will review the current status of DMT in Parkinson’s disease, highlighting the most promising biological targets of interest as well as the ongoing challenges in this field.