Emerging non-invasive therapeutic approaches targeting hypocholinergic neural systems in Parkinson's disease

摘要

Cholinergic system associated DOPA-refractory motor and cognitive symptoms-a need for novel therapeutic approaches:Accumulating evidence points to significant motor and non-motor morbidities associated with hypocholinergic deficits in central and peripheral neural systems in Parkinson’s disease(PD)(Bohnen et al.,2018,2022).This so-called“malignant”hypocholinergic disease phenotype is associated with DOPA-refractory dementia and mobility disturbances,such as falls and freezing of gait,and augur novel therapeutic approaches targeting cholinergic systems in PD.Cholinergic pharmacotherapy in PD has been an interest for a long time.However,the development of cholinergic augmentation pharmacotherapy has been hampered by limited clinical efficacy,the presumption that changes in cholinergic activity are homogeneous in the central nervous system(CNS)and peripheral nervous system,tolerance or safety of cholinesterase inhibitor drugs,low CNS penetrance,high rate of peripheral autonomic side-effects and clinical contra-indications.The development of nicotinic or muscarinic receptor modulating drugs appears more promising but is still in the development stage.Given the current unmet need for managing DOPA-refractory cognitive and mobility impairments associated with hypocholinergic neural systems,there is a need for novel and complementary therapeutic and more personalized approaches.