Novel targeted therapies for Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second more common neurodegenerative disease with increasing incidence worldwide associated to the population ageing. Despite increasing awareness and significant research advancements, treatment options comprise dopamine repleting, symptomatic therapies that have significantly increased quality of life and life expectancy, but no therapies that halt or reverse disease progression, which remain a great, unmet goal in PD research. Large biomarker development programs are undertaken to identify disease signatures that will improve patient selection and outcome measures in clinical trials. In this review, we summarize PD-related mechanisms that can serve as targets of therapeutic interventions aiming to slow or modify disease progression, as well as previous and ongoing clinical trials in each field, and discuss future perspectives.

Fat and Protein Combat Triggers Immunological Weapons of Innate and Adaptive Immune Systems to Launch Neuroinflammation in Parkinson’s Disease

“…As the gold standard of treatment for PD, levodopa and its derivatives are only the standard care for PD patients [417]. However, such therapies do not alter the disease's course, and nor do they stop or reverse the brain inflammation, which often has the greatest impact on quality of life [418,419]. Additionally, the long-term use of these drugs has been linked to several adverse effects, such as fluctuations, dyskinesia, toxicity, or loss of efficacy [420].…”

Immunotherapies for Neurodegenerative Diseases

“…GLP-1 agonists reduce proinflammatory cytokines and reduce disease burden in AD and PD mouse models. The mechanisms detailing the mode of action of these drugs and their pathways have been extensively reviewed (85)(86)(87). Nevertheless, recent results obtained from AD and PD clinical trials for GLP-1 agonist drugs have shown minor improvements in disease pathophysiology, if any (88)(89)(90)(91).…”

“…Pre-clinically, PPARγ agonists have been shown to reduce neuroinflammation, Aβ-42 load, phosphorylated tau, and synaptophysin, ultimately enhancing spatial memory and motor function in AD mouse models (81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93). Furthermore, two promising PPAR-γ agonists currently under phase II clinical trials, T3D-959 (NCT04251182), and Pioglitazone (NCT00982202), have proven their safety and tolerability among patients (94,95).…”

The PINK1-Mediated Crosstalk between Neural Cells and the Underlying Link to Parkinson’s Disease

“…Even though there are other therapeutic approaches under development and continuous clinical trials ongoing, such as gene therapies, immunotherapies targeting α-synuclein, or stem cell-based treatments, levodopa is at present the most commonly used treatment for PD patients as it significantly reduces motor symptoms [93,94]. However, and in order to develop novel treatments for PD, it is important to decipher the molecular mechanisms responsible for neuronal death and ultimately disease progression by taking into account overall brain homeostasis.…”