Comparative efficacy of surgical approaches to disease modification in Parkinson disease

Abstract

Parkinson’s disease (PD) may optimally be treated with a disease-modifying therapy to slow progression. We compare data underlying surgical approaches proposed to impart disease modification in PD: (1) cell transplantation therapy with stem cell-derived dopaminergic neurons to replace damaged cells; (2) clinical trials of growth factors to promote survival of existing dopaminergic neurons; (3) subthalamic nucleus deep brain stimulation early in the course of PD; and (4) abdominal vagotomy to lower risk of potential disease spread from gut to brain. Though targeted to engage potential mechanisms of PD these surgical approaches remain experimental, indicating the difficulty in translating therapeutic concepts into clinical practice. The choice of outcome measures to assess disease modification separate from the symptomatic benefit will be critical to evaluate the effect of the disease-modifying intervention on long-term disease burden, including imaging studies and clinical rating scales, i.e., Unified Parkinson Disease Rating Scale. Therapeutic interventions will require long follow-up times (i.e., 5–10 years) to analyze disease modification compared to symptomatic treatments. The promise of invasive, surgical treatments to achieve disease modification through mechanistic approaches has been constrained by the reality of translating these concepts into effective clinical trials.

Update to the Treatment of Parkinson’s Disease Based on the Gut-Brain Axis Mechanism

“…This is because although it can reduce the risk of developing PD, it can also lead to serious complications such as dysphagia, vomiting, and diarrhea, which can have incalculable side effects on the intestines, brain, and other organs. Therefore, effective screening of people at risk for PD, and thus necessary early intervention, is crucial ( Rahimpour et al, 2022 ).…”

Accelerated neuronal aging in vitro ∼melting watch ∼

“…Approaches for mechanistic elucidation of the onset and progression in various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) have led to the development of disease-modifying therapies to prevent neurodegeneration itself ( Kritsilis et al, 2018 ; Hou et al, 2019 ; Bobkova et al, 2020 ; Gendron et al, 2020 ). There are several potential candidates for disease-modifying therapies for ALS, AD, and PD, including AAV-mediated gene therapies and antibody-based approaches and cell transplantation ( Doi et al, 2020 ; Amado and Davidson, 2021 ; Tampi et al, 2021 ; Cummings et al, 2022 ; Rahimpour et al, 2022 ; Shi et al, 2022 ; Takahashi and Mashima, 2022 ). However, these approaches are yet under clinical trials or debates, and not thoroughly validated in human.…”