New and Emerging Therapies in Parkinson’s Disease
As the therapeutic landscape expands, an increasing range of options and a promising horizon will improve management of motor fluctuations for many patients with Parkinson’s disease.
By Laxman Bahroo, DO, Fahd Amjad, MD, Khashayar Dhastipour, MD, and Fernando Pagan, MD
Parkinson’s disease (PD) impairs motor, sensory, autonomic and cognitive functions. In particular, management of motor fluctuations remains an unmet need in patients with PD. Continuous dopaminergic stimulation (CDS) reduces motor complications in animal models, while motor complication management in advanced PD focuses on extending the duration of levodopa with adjunctive medication.
Two new levodopa agents headline the newest innovations in therapeutic development in Parkinson’s disease treatment. One is a longer acting oral formulation and the other is delivered via a PEG-J tube to smoothen delivery and improve motor fluctuations. Emerging therapies such as apomorphine infusion and inhaled levodopa use novel delivery systems of existing compounds that bypass the gastrointestinal system, while novel compounds, such as safinimide, offer a unique mechanism of action, provide higher degree of selectivity and potentially less drug interaction. Beyond these novel compounds and delivery systems, the next great challenge in Parkinson’s management is the development of medications that potentially modify the course of the disease.
Parkinson’s Disease at 200 Years: Progress, New Faces, and Unmet Needs
Anthony E. Lang, OC, MD, FRCPC, FAAN, FCAHS, FRSC, Professor, University of Toronto, Department of Medicine; Director, Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital; Director, Division of Neurology, University of Toronto
- Due to the increasing longevity of the world’s population it has been predicted that the number of individuals with PD over age 50 in Western Europe’s five most and the world’s 10 most populous nations will double from 2005 estimates of 4.1-4.6 million in 2005 to between 8.7-9.3 million by 2030.
- The Holy Grail of Parkinson’s disease is the development of effective neuroprotective therapy which, in the future if introduced early enough in the disease course (i.e. in the prodromal stage) could even prevent the eventual development of those features that we now require to make a diagnosis. To date, all attempts to define effective neuroprotective/disease modifying therapy have failed.
- One critical factor, applicable to all neurodegenerative diseases, is when in the course of the disease process the treatment is applied. Indeed, it has been known for some time that the classical motor features of PD don’t become manifest until 50-70% of nigral dopaminergic cells are lost and Braak’s work has emphasized that the disease is entrenched in other areas well before the nigra is first affected. Beginning neuroprotective therapy even at the first appearance of clinical features of PD (Braak’s Stage 3) may be analogous to closing the barn door long after the horse has bolted. Thus, the clear need for various biomarkers of early disease.
Many Parkinson’s Disease Programs in Development, GBI Research Reports
The current Parkinson’s disease (PD) treatment market relies on neuromodulators, and even though symptoms might be soothed, no neuromodulator has demonstrated neuroprotective properties to prevent or even slow down neuronal cell death.
However, the pipeline for PD is highly active, with 365 programs in all development stages and with diverse ranges of molecular targets.
“While neuromodulators remain dominant in the pipeline, there are a number of targets which address different pathogenic mechanisms underlying neurodegeneration in Parkinson’s disease. This demonstrates a shift from traditional symptomatic treatments to disease-modifying therapies.”