Recent failures of new potential symptomatic treatments for parkinson's disease: Causes and solutions
Identifieur interne : 003B62 ( Main/Exploration ); précédent : 003B61; suivant : 003B63Recent failures of new potential symptomatic treatments for parkinson's disease: Causes and solutions
Auteurs : Gurutz Linazasoro [Espagne]Source :
- Movement Disorders [ 0885-3185 ] ; 2004-07.
Descripteurs français
- Pascal (Inist)
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), Nervous system diseases, Neurons (metabolism), Neurons (transplantation), Neurosurgical Procedures (methods), Oxidopamine (adverse effects), Parkinson Disease (complications), Parkinson Disease (etiology), Parkinson Disease (therapy), Parkinson disease, Parkinson's disease, Treatment, Treatment Failure, animal models, motor complications, treatment alternatives.
- 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. © 2004 Movement Disorder Society
Url:
DOI: 10.1002/mds.20120
Affiliations:
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Le document en format XML
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Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2004-07">2004-07</date><biblScope unit="vol">19</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="743">743</biblScope><biblScope unit="page" to="754">754</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">C65C73A2D1522F6DEF3CC5AAE98A8F0F666509C8</idno><idno type="DOI">10.1002/mds.20120</idno><idno type="ArticleID">MDS20120</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (adverse effects)</term><term>Adrenergic Agents (adverse effects)</term><term>Animals</term><term>Antiparkinson Agents (classification)</term><term>Antiparkinson Agents (therapeutic use)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopamine Agents (adverse effects)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Electric Stimulation Therapy (instrumentation)</term><term>Globus Pallidus (surgery)</term><term>Humans</term><term>Levodopa (adverse effects)</term><term>Levodopa (therapeutic use)</term><term>Movement Disorders (drug therapy)</term><term>Movement Disorders (etiology)</term><term>Movement Disorders (therapy)</term><term>Nervous system diseases</term><term>Neurons (metabolism)</term><term>Neurons (transplantation)</term><term>Neurosurgical Procedures (methods)</term><term>Oxidopamine (adverse effects)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (etiology)</term><term>Parkinson Disease (therapy)</term><term>Parkinson disease</term><term>Parkinson's disease</term><term>Treatment</term><term>Treatment Failure</term><term>animal models</term><term>motor complications</term><term>treatment alternatives</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Adrenergic Agents</term><term>Dopamine Agents</term><term>Levodopa</term><term>Oxidopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="classification" xml:lang="en"><term>Antiparkinson Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Movement Disorders</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Movement Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="instrumentation" xml:lang="en"><term>Electric Stimulation Therapy</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Neurosurgical Procedures</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Globus Pallidus</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Movement Disorders</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Treatment Failure</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term><term>Système nerveux pathologie</term><term>Traitement</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><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. 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