Recent failures of new potential symptomatic treatments for Parkinson's disease: causes and solutions.
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.
Linazasoro
Gurutz
G
Centro de Neurología y Neurocirugía funcional, Clínica Quirón, San Sebastián, Guipúzcoa, Spain.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D018663:Adrenergic Agents / Q000009:adverse effects; D000818:Animals; D000978:Antiparkinson Agents / Q000145:classification / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D004599:Electric Stimulation Therapy / Q000295:instrumentation; D005917:Globus Pallidus / Q000601:surgery; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology* / Q000628:therapy*; D009474:Neurons / Q000378:metabolism / Q000637:transplantation; D019635:Neurosurgical Procedures / Q000379:methods; D016627:Oxidopamine / Q000009:adverse effects; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology / Q000628:therapy*; D017211:Treatment Failure
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine