The Development of Treatment for Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a slowly progressive, age-related, second most common neurodegenerative disorder after Alzheimer's disease of unknown etiology. Dopamine replacement therapies were introduced five decades ago and still remain the mainstay of treatment for Parkinson's disease. However, with long-term treatment with L-dopa, more than 50% of patients were found to develop motor response complications approximately after 4-5 years of initiation of continuous treatment, in 80% of patients treated for 10 years, and in nearly 100% patients with young-onset disease. The complications of long-term treatment with levodopa include-motor fluctuations, dyskinesias, and nonmotor fluctuations are such as mood disturbance, cognitive dysfunction, dysautonomia and pain. Till date, there are various therapeutic approaches having been developed for the treatment of advanced PD comprising Pharmacotherapy, neurotrophic factors, surgical procedures such as DBS, cell-based therapies and gene therapies. The pharmacological and surgical therapies are only aiming to improve the symptoms of PD, but none are proven to have a significant effect on the underlying disease process with respect to either slowing disease progression or restoring the affected dopaminergic neurons. Although there is no cure for PD, Gene based therapy has significant prospective advantages over the conventional treatment modalities for PD, as it could theoretically be used to preserve or restore dopaminergic neurons affected by PD through the action of neurotrophic factors or alternatively increase the availability of enzymes required for dopamine synthesis. All commonly employed PD therapies focus on the amelioration of symptoms and do not cure disease. In this review only we summarize the newer therapeutic strategies for the treatment of PD such as anti-inflammatories, neurotrophic factors, neurosurgical procedures (DBS), cell based therapies and gene therapies.

Nigrostriatal interaction in the aging brain: new therapeutic target for Parkinson’s disease

“…Parkinson's disease (PD) represents the second most common neurodegenerative disorder that is clinically characterized by non-motor and motor symptoms (Błaszczyk 1998, Chaudhuri et al 2006, Pellicano et al 2007, Schapira 2008, Yadav and Li 2015. The etiology and pathogensis of PD still remains unclear, but it is thought that it may be caused by a combination of genetic and environmental factors (Braak et al 2004, Schapira 2007, Mosharov et al 2009, Brichta and Greengard 2014, Yadav and Li 2015, Goedert 2015. It is well documented that the cardinal features of PD motor symptoms including bradykinesia, muscular rigidity, rest tremor, and postural and gait instability can be entirely explained by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (Cenci 2007, Pellicano et al 2007, Fahn 2008, Brichta and Greengard 2014, Yadav and Li 2015.…”

“…It is well documented that the cardinal features of PD motor symptoms including bradykinesia, muscular rigidity, rest tremor, and postural and gait instability can be entirely explained by degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) (Cenci 2007, Pellicano et al 2007, Fahn 2008, Brichta and Greengard 2014, Yadav and Li 2015. Consequently, treatment for PD has classically involved supplementation of endogenous dopamine (DA) with medicinal options that either replace dopamine or augment the nigrostriatal dopaminergic pathway (Schapira 2007, Fahn 2008, Yadav and Li 2015. Surprisingly, all current pharmacological therapies and surgical treatments, including deep brain stimulation and stem cell therapy, are oriented towards symptomatic relief and do not cure disease (Schapira 2007, Yadav andLi 2015).…”

“…Consequently, treatment for PD has classically involved supplementation of endogenous dopamine (DA) with medicinal options that either replace dopamine or augment the nigrostriatal dopaminergic pathway (Schapira 2007, Fahn 2008, Yadav and Li 2015. Surprisingly, all current pharmacological therapies and surgical treatments, including deep brain stimulation and stem cell therapy, are oriented towards symptomatic relief and do not cure disease (Schapira 2007, Yadav andLi 2015). Our current knowledge why the SNpc dopaminergic neurons are particularly vulnerable to degeneration is still extremely limited (Pissadaki and Bolam 2013, Brichta and Greengard 2014, Dopeso-Reyes et al 2014, and without this knowledge, development of a promising neuroprotective treatment strategy is not possible.…”

Population pharmacokinetic and pharmacodynamic analyses of safinamide in subjects with Parkinson's disease

“…Parkinson's disease (PD) is the second most common chronic progressive neurodegenerative disorder in the elderly after Alzheimer's disease (Yadav and Li 2015). The disease is characterized by dopamine deficiency resulting from progressive loss of nigrostriatal dopaminergic cells (Schapira 2011), and its diagnosis is mainly based on observational criteria of muscular rigidity, resting tremor, or postural instability in combination with bradykinesia (Grosset et al 2010).…”

Improvement of oral function and hygiene in Parkinson's disease: A randomised controlled clinical trial

“…3 Patients with PD have jaw tremor, and rigid facial and masticatory muscles as well as poorer jaw function than subjects without PD. 3 Patients with PD have jaw tremor, and rigid facial and masticatory muscles as well as poorer jaw function than subjects without PD.…”