Chapter 24 - Pipeline of Pharmacotherapy in Parkinson’s Disease

Summary

Many drugs are available to treat Parkinson’s disease (PD), but are limited to alleviating symptoms; no disease-modifying treatment (DMT) has been approved by any authority. There is much effort to develop remedies capable of altering the underlying neurodegenerative processes in PD. Current concepts target the deposition of pathologic α-synuclein oligomers either by immunization strategies or by small molecules that interact with the protein aggregation. Further DMT approaches modulate pathologically active intracellular processes such as the c-Abl kinase or LRRK2 pathway or aim to activate signaling pathways involved in neuroprotection, such as the GLP-1 receptor pathway (with GLP1-agonist exenatide being the most advanced DMT in the PD drug pipeline). Replacement of enzymes such as β-glucocerebrosidase, modification of the microbiome, or targeting energy metabolism or inflammation are further approaches proposed to slow down neurodegeneration. Novel symptomatic treatment approaches envisage improvement of pharmacologic properties of levodopa or dopamine agonists or target non-dopaminergic neurotransmitter systems, e.g., the glutamatergic, serotoninergic or cholinergic system.