Disease modification in Parkinsonism: obstacles and ways forward

Abstract

To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.

WITHDRAWN: Screening and identification of the potential diagnostic genes for Parkinson's Disease based on Machine Learning algorithm

“…The clinic symptoms of PD usually appear slowly over time, including motor system dysfunction mainly characterized myotonia, static tremor, movement retardation and gait abnormalities, as well as non-motor symptoms such as dementia and cognitive problems [20]. Due to the lack of speci c diagnostic indicators, the diagnosis of PD presently mainly relies on the clinical symptoms and imaging examination results that already appeared, which brings major di culties to the early diagnosis of patients with PD [21]. Therefore, researchers are turning their attention to potential genetic markers of PD, attempting to identify the potential pathological genes and mechanisms of PD from a perspective of genetic, to assist in the early diagnosis of PD and explore novel therapy.…”

Epidemiology of Progressive Supranuclear Palsy: Real World Data from the Second Largest Health Plan in Israel

“…Once diagnosed, PSP is a fatal disease where the median survival time ranges between 5 and 8 years, but differs between PSP phenotypes, with shorter life expectancy in patients with RS phenotypes as compared to non RS phenotypes [ 6 , 10 ]. While PSP’s fatality rises, there are no approved disease modifying therapies (DMT) [ 11 , 12 ]. Furthermore, satisfying symptomatic treatment is also lacking.…”

Whole‐Brain Magnetic Resonance Spectroscopy Reveals Distinct Alterations in Neurometabolic Profile in Progressive Supranuclear Palsy

“…It is still unclear how these clinical diagnostic criteria translate into more specific detection of the four‐repeat tauopathy antemortem, which is characteristic of PSP 3 . The exact detection of the underlying pathology in patients with PSP is crucial for future disease modifying treatments 4 . However, in the first years of the disease, the determination of the specific neuropathology may be troublesome and less accurate when based only on clinical findings 5 .…”