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Journal of Parkinson's Disease 2020The majority of current pharmacological treatments for Parkinson's disease (PD) were approved for clinical use in the second half of the last century and they only... (Review)
Review
BACKGROUND
The majority of current pharmacological treatments for Parkinson's disease (PD) were approved for clinical use in the second half of the last century and they only provide symptomatic relief. Derivatives of these therapies continue to be explored in clinical trials, together with potentially disease modifying therapies that can slow, stop or reverse the condition.
OBJECTIVE
To provide an overview of the pharmacological therapies- both symptomatic and disease modifying- currently being clinically evaluated for PD, with the goal of creating greater awareness and opportunities for collaboration amongst commercial and academic researchers as well as between the research and patient communities.
METHODS
We conducted a review of clinical trials of drug therapies for PD using trial data obtained from the ClinicalTrials.gov database and performed a breakdown analysis of studies that were active as of January 21, 2020.
RESULTS
We identified 145 registered and ongoing clinical trials for therapeutics targeting PD, of which 51 were Phase 1 (35% of the total number of trials), 66 were Phase 2 (46% ), and 28 were Phase 3 (19% ). There were 57 trials (39% ) focused on long-term disease modifying therapies, with the remaining 88 trials (61% ) focused on therapies for symptomatic relief. A total of 50 (34% ) trials were testing repurposed therapies.
CONCLUSION
There is a broad pipeline of both symptomatic and disease modifying therapies currently being tested in clinical trials for PD.
Topics: Antiparkinson Agents; Clinical Trials as Topic; Drug Development; Humans; Neuroprotective Agents; Parkinson Disease; Treatment Outcome
PubMed: 32741777
DOI: 10.3233/JPD-202128 -
Neurotherapeutics : the Journal of the... Jan 2014Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has... (Review)
Review
Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.
Topics: Animals; Antiparkinson Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Parkinson Disease
PubMed: 24158912
DOI: 10.1007/s13311-013-0234-1 -
Current Neuropharmacology 2016Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are... (Review)
Review
BACKGROUND
Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy.
METHODS
This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches.
RESULTS
It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease.
CONCLUSION
Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.
Topics: Animals; Antiparkinson Agents; Blood-Brain Barrier; Brain; Dopamine Plasma Membrane Transport Proteins; Drug Delivery Systems; Humans; Nanocapsules; Nanoparticles; Parkinson Disease; Receptors, Dopamine
PubMed: 26714584
DOI: 10.2174/1570159x14666151230124904 -
European Neurology 2009Levodopa has been the mainstay of treatment for Parkinson's disease (PD) for more than 40 years. During this time, researchers have strived to optimize levodopa... (Review)
Review
Levodopa has been the mainstay of treatment for Parkinson's disease (PD) for more than 40 years. During this time, researchers have strived to optimize levodopa formulations to minimize side effects, enhance central nervous system (CNS) bioavailability, and achieve stable therapeutic plasma levels. Current strategies include concomitant treatment with inhibitors of dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT) to prolong the peripheral levodopa half-life and increase CNS bioavailability. Levodopa combined with DDC inhibition is the current standard method of delivering levodopa for symptomatic treatment of PD. Recent research suggests that continuous dopaminergic stimulation that more closely approximates physiological stimulation may delay or prevent the development of motor fluctuations ('wearing off') and dyskinesias. Strategies currently being used to achieve more continuous dopaminergic stimulation include the combination of an oral levodopa/DDC inhibitor with a COMT inhibitor and the enteral infusion of a levodopa gel formulation. Attempts are underway to develop oral and transdermal very long-acting levodopa preparations.
Topics: Antiparkinson Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Brain; Catechol O-Methyltransferase Inhibitors; History, 20th Century; History, 21st Century; Humans; Levodopa; Models, Neurological; Parkinson Disease
PubMed: 19407449
DOI: 10.1159/000215875 -
Drugs in R&D Jun 2018Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with... (Review)
Review
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges. From shamanic rituals in ancient Egypt and Mesoamerica, to the treatment of erectile dysfunction, from being discarded as a pharmacological tool to becoming an essential antiparkinsonian drug, the path of apomorphine in the therapeutic armamentarium has been tortuous and punctuated by setbacks and groundbreaking discoveries. Throughout history, three main clinical indications stood out: emetic (gastric emptying, respiratory disorders, aversive conditioning), sedative (mental disorders, clinical anesthesia, alcoholism), and antiparkinsonian (fluctuations). New indications may arise in the future, both in PD (palliative care, nonmotor symptoms, withdrawal of oral dopaminergic medication), and outside PD, with promising work in neuroprotection or addiction.
Topics: Animals; Antiparkinson Agents; Apomorphine; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans
PubMed: 29546602
DOI: 10.1007/s40268-018-0230-3 -
Toxins Jan 2021For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly,... (Review)
Review
For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. Thus, BoNT is used for patients with Parkinson's disease (PD) and other Parkinson's syndromes (PS) in varying degrees of frequency. We have to distinguish between (1) indications that are either approved or (2) those not approved, (3) indications that might be a result of PS and (4) finally those which appear independent of PS. The most important indication for BoNT in PS patients is probably sialorrhea, for which approval has been granted in the majority of countries. Cervical dystonia is a frequent symptom in PS, with anterocollis as a specific entity. A further indication is blepharospasm in the different forms, especially the inhibition of eyelid opening in atypical PS. The use of BoNT in cases of camptocormia, the Pisa syndrome and neck rigidity is still a matter of debate. In dystonia of the extremities BoNT can be recommended, especially in dystonia of the feet. One well-known indication, for which however sufficient data are still lacking, involves treating tremor with BoNT. As to autonomic symptoms: Focal hyperhidrosis and detrusor hyperactivity can be mentioned, in this last case BoNT has already been approved. A number of further but rare indications such as freezing-of-gait, dyskinesia, and dysphagia will be discussed and evaluated.
Topics: Acetylcholine Release Inhibitors; Animals; Antiparkinson Agents; Botulinum Toxins; Humans; Motor Activity; Parkinson Disease; Treatment Outcome
PubMed: 33503872
DOI: 10.3390/toxins13020087 -
Revista Brasileira de Psiquiatria (Sao... Apr 2020
Topics: Antiparkinson Agents; Cannabidiol; Humans; Parkinson Disease; Treatment Outcome
PubMed: 32187321
DOI: 10.1590/1516-4446-2019-0810 -
Neurologia Sep 2020
Topics: Alanine; Antiparkinson Agents; Benzylamines; Sexuality
PubMed: 30551909
DOI: 10.1016/j.nrl.2018.07.004 -
American Family Physician Dec 2006Parkinson's disease is a common neurodegenerative disorder that can cause significant disability and decreased quality of life. The cardinal physical signs of the... (Review)
Review
Parkinson's disease is a common neurodegenerative disorder that can cause significant disability and decreased quality of life. The cardinal physical signs of the disease are distal resting tremor, rigidity, bradykinesia, and asymmetric onset. Levodopa is the primary treatment for Parkinson's disease; however, its long-term use is limited by motor complications and drug-induced dyskinesia. Dopamine agonists are options for initial treatment and have been shown to delay the onset of motor complications. However, dopamine agonists are inferior to levodopa in controlling motor symptoms. After levodopa-related motor complications develop in advanced Parkinson's disease, it is beneficial to initiate adjuvant therapy with dopamine agonists, catechol O-methyltransferase inhibitors, or monoamine oxidase-B inhibitors. Deep brain stimulation of the subthalamic nucleus has been shown to ameliorate symptoms in patients with advanced disease. Depression, dementia, and psychosis are common psychiatric problems associated with Parkinson's disease. Psychosis is usually drug induced and can be managed initially by reducing antiparkinsonian medications. The judicious use of psychoactive agents may be necessary. Consultation with a subspecialist is often required.
Topics: Algorithms; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Diagnosis, Differential; Dopamine Agonists; Humans; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Parkinson Disease
PubMed: 17186710
DOI: No ID Found -
The American Journal of Managed Care Oct 2011Parkinson's disease (PD) is a common neurodegenerative disorder diagnosed by the presence of bradykinesia and at least 1 of the symptoms of rigidity, resting tremor, or... (Review)
Review
Parkinson's disease (PD) is a common neurodegenerative disorder diagnosed by the presence of bradykinesia and at least 1 of the symptoms of rigidity, resting tremor, or postural instability. It is increasingly recognized that nonmotor symptoms are common and can adversely affect quality of life, yet they often are not diagnosed and consequently are often untreated. Nonmotor symptoms include neuropsychiatric issues such as anxiety, depression, hallucinations, impulse control disorders, and cognitive impairment, as well as autonomic dysfunction, which may present as gastrointestinal, urinary, and sexual disturbances. Nonmotor symptoms also include excessive sweating, orthostatic hypotension, and sleep disturbances. Management of PD requires recognition of both motor and nonmotor symptoms as well as an understanding of the relationship between these symptoms and how they can be affected by treatments for PD. Therapy should be individualized for each patient, as treatments for the motor symptoms of PD can improve some nonmotor symptoms while they can worsen others. In many cases, symptom-specific treatments are necessary to control nonmotor symptoms of PD.
Topics: Antiparkinson Agents; Autonomic Nervous System Diseases; Behavioral Symptoms; Cognition Disorders; Humans; Mental Disorders; Parkinson Disease; Quality of Life; Sickness Impact Profile; Sleep Disorders, Intrinsic
PubMed: 22087551
DOI: No ID Found