Newly Approved and Investigational Drugs for Motor Symptom Control in Parkinson's Disease

Abstract

Motor symptoms are a core feature of Parkinson’s disease (PD) and cause a significant burden on patients’ quality of life. Oral levodopa is still the most effective treatment, however, the motor benefits are countered by inherent pharmacologic limitations of the drug. Additionally, with disease progression, chronic levodopa leads to the appearance of motor complications including motor fluctuations and dyskinesia. Furthermore, several motor abnormalities of posture, balance, and gait may become less responsive to levodopa. With these unmet needs and our evolving understanding of the neuroanatomic and pathophysiologic underpinnings of PD, several advances have been made in defining new therapies for motor symptoms. These include newer levodopa formulations and drug delivery systems, refinements in adjunctive medications, and non-dopaminergic treatment strategies. Although some are in early stages of development, these novel treatments potentially widen the available options for the management of motor symptoms allowing clinicians to provide an individually tailored care for PD patients. Here, we review the existing and emerging interventions for PD with focus on newly approved and investigational drugs for motor symptoms, motor fluctuations, dyskinesia, and balance and gait dysfunction.

Non‐lesional treatments for tremor in Parkinson's disease: A systematic review and meta‐analysis

“…Nevertheless, a genetic variant of the D3 receptor relates to the risk and the severity of essential tremor [56] possibly supporting the role of dopamine receptor subtypes in the pathophysiology of tremor. This corroborates the claims for further scrutiny on subtypes of dopamine receptor for alleviation of specific iPD symptoms [57]. Although our results suggest the primary use of dopamine agonists other than ropinirole, further studies with direct comparisons could render clinical support to our findings.…”

“…Nevertheless, a genetic variant of the D3 receptor relates to the risk and the severity of essential tremor [56] possibly supporting the role of dopamine receptor subtypes in the pathophysiology of tremor. This corroborates the claims for further scrutiny on subtypes of dopamine receptor for alleviation of specific iPD symptoms [57].…”

Noradrenaline and Movement Initiation Disorders in Parkinson’s Disease: A Pharmacological Functional MRI Study with Clonidine

“…Although no convincing solution has been provided to date [ 2 , 4 ], the present results might have important implications in setting the ground for new add-on NA treatment approaches. Yet, further pharmacological investigations are warranted to support this hypothesis.…”

“…Although Parkinson’s disease (PD) has long been considered a motor and dopaminergic disease, numerous non-dopaminergic neurotransmitter systems are implicated in its motor features ( Figure 1 A) [ 1 ]. Current drugs that modulate the acetylcholinergic, glutamatergic, histaminergic, adenosinergic, GABAergic, serotonergic or noradrenergic (NA) systems might thus provide clinical benefits as add-on therapies to L-dopa by targeting symptoms that may be mediated by nondopaminergic systems [ 1 , 2 , 3 , 4 ]. However, the neurochemical bases of numerous motor subfunctions and non-motor functions that modulate movement control are still obscure, making it difficult to associate symptoms with potentially relevant pharmacological solutions.…”

Extrapiramidális kórképek • Movement Disorders

“…Az ezen a területen elért eredmények tették lehetővé a személyre szabott (genetikai) terápiák megjelenését ezekben a kórállapotokban (Huntington-kór, LRRK2-mutációhoz köthető Parkinson-kór, SOD1-mutációs ALS stb.) (Di Luca et al, 2022). Ezek sajnálatos módon még csak a betegek kis százalékát érintik, de tudományos jelentőségük ezen túlmutat, hiszen teljesen új kezelési elvek kialakítását eredményezte.…”