Recent failures of new potential symptomatic treatments for Parkinson's disease: causes and solutions.
Identifieur interne : 000E63 ( Ncbi/Curation ); précédent : 000E62; suivant : 000E64Recent failures of new potential symptomatic treatments for Parkinson's disease: causes and solutions.
Auteurs : Gurutz Linazasoro [Espagne]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2004.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (adverse effects), Adrenergic Agents (adverse effects), Animals, Antiparkinson Agents (classification), Antiparkinson Agents (therapeutic use), Disease Models, Animal, Dopamine (metabolism), Dopamine Agents (adverse effects), Dyskinesia, Drug-Induced (etiology), Electric Stimulation Therapy (instrumentation), Globus Pallidus (surgery), Humans, Levodopa (adverse effects), Levodopa (therapeutic use), Movement Disorders (drug therapy), Movement Disorders (etiology), Movement Disorders (therapy), Neurons (metabolism), Neurons (transplantation), Neurosurgical Procedures (methods), Oxidopamine (adverse effects), Parkinson Disease (complications), Parkinson Disease (etiology), Parkinson Disease (therapy), Treatment Failure.
- MESH :
- chemical , adverse effects : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Adrenergic Agents, Dopamine Agents, Levodopa, Oxidopamine.
- chemical , classification : Antiparkinson Agents.
- chemical , metabolism : Dopamine.
- chemical , therapeutic use : Antiparkinson Agents, Levodopa.
- complications : Parkinson Disease.
- drug therapy : Movement Disorders.
- etiology : Dyskinesia, Drug-Induced, Movement Disorders, Parkinson Disease.
- instrumentation : Electric Stimulation Therapy.
- metabolism : Neurons.
- methods : Neurosurgical Procedures.
- surgery : Globus Pallidus.
- therapy : Movement Disorders, Parkinson Disease.
- transplantation : Neurons.
- Animals, Disease Models, Animal, Humans, Treatment Failure.
Abstract
One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine-lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed.
DOI: 10.1002/mds.20120
PubMed: 15254931
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<term>Animals</term>
<term>Antiparkinson Agents (classification)</term>
<term>Antiparkinson Agents (therapeutic use)</term>
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<term>Dopamine (metabolism)</term>
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<front><div type="abstract" xml:lang="en">One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine-lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed.</div>
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