What were the basic science and clinical study highlights from 2020 in Parkinson’s disease? The high-impact scientific discoveries and clinical studies were selected and critically reviewed by Professor Tyosuke Takahashi, Kyoto, Japan and Professor Shen-Yang Lim, Kuala Lumpur, Malaysia, respectively, at MDS Virtual Congress 2020.
High-impact scientific discoveries in 2020
New discoveries are revealing many potential molecular targets
Professor Takahashi’s selection and review of Parkinson’s disease (PD) basic science highlights included studies that provided evidence for:
- prevention of α-synuclein aggregation by molecular chaperones through interaction with the N-terminus of α-synuclein1
- role of the general circulation as a potential route for the bidirectional transmission of endogenous α-synuclein between the enteric and the central nervous systems2
- a role for microglial exosomes in the progression of α-synuclein pathology3
- a neuroprotective function for microglia by clearing α-synuclein via Toll-like receptor 4-NF-κB-p62-mediated engulfment into autophagosomes for degradation4
- the contribution of R type voltage-gated calcium channels (Cav2.3) to neuron loss in a PD mouse model5
- a role for senescence of dopamine neurons in the development of PD associated with loss of DNA-binding protein SATB1, which prevents cellular senescence6
High-impact clinical studies in 2020
57 registered or ongoing clinical trials are investigating DMTs for PD
Professor Lim’s selection and review of clinical studies focused on phase 2 or phase 3 trials with an emphasis on disease-modifying therapies (DMTs).
Of the 145 registered and ongoing phase 1–3 clinical trials investigating drug therapy for Parkinson’s disease, 57 are investigating DMTs, he said.7 The remaining 88 trials are investigating symptomatic relief. Repurposed therapies are being evaluated in 50 of these trials.7
These DMTs have many different mechanisms of action and act at many different biological levels ranging from the microbiome through to targeting α-synuclein.
DMTs being investigated have many different mechanisms of action
Ongoing DMT trials highlighted and reviewed by Professor Lim are investigating:
- monoclonal antibodies targeting α-synuclein, which have already been found to be safe and well tolerated in a 1b trial in 20188
- repurposed already-licensed therapies targeting bioenergetics and mitochondrial function, for example a phase 2 trial exploring the potential of ursodeoxycholic acid9
- precision medicine approaches that target genetic forms of PD—such as PD associated with mutations in the glucocerebrosidase (GBA), for example gene therapy and small molecule chaperones; and leucine-rich repeat kinase 2 (LRRK2) genes, for example LRRK2 inhibitors10
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Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.