Document Detail


New small molecules for the treatment of Parkinson's disease.
MedLine Citation:
PMID:  20645881     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IMPORTANCE OF THE FIELD: Parkinson's disease (PD) is characterized by a slowly ongoing neuronal death, which affects neurotransmitter metabolism and causes a wide variety of motor and non-motor features. Until now, therapy approaches have predominantly focused on motor behavior associated with dopamine substitution.
AREAS COVERED IN THIS REVIEW: This review aims to discuss putative reasons for recent failures of investigated treatment approaches, and to introduce currently tested and future compounds.
WHAT THE READER WILL GAIN: We will describe how development programs of novel molecules now additionally consider non-motor features of PD as promising targets in order to obtain regulatory approval. Regulatory authorities increasingly exert influence on trial designs, demanding therapeutic effects that are not always clinically feasible given the variety of manifestations of the disease entity known as PD.
TAKE HOME MESSAGE: In the past, research pitfalls have resulted in the failure of promising new compounds. Among the many reasons for this are massive placebo responses; the participation of too many investigators, with consequent wide variations of efficacy assessments; and a misconception of preclinical drug development, with models of PD that do not mimic its clinical nature. A few compounds are now being tested that have modes of action indirectly modulating the dopamine system; however, critical analysis of the preclinical and clinical research concept and drug approval is warranted to prevent further frustration in this field.
Authors:
Thomas Müller
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  19     ISSN:  1744-7658     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2011-01-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1077-86     Citation Subset:  IM    
Affiliation:
St. Joseph Hospital Berlin-Weissensee, Department of Neurology, Gartenstrasse 1, 13088 Berlin, Germany. th.mueller@alexius.de
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MeSH Terms
Descriptor/Qualifier:
Antiparkinson Agents / pharmacology,  therapeutic use*
Clinical Trials as Topic
Disease Progression
Dopamine / metabolism
Drug Evaluation, Preclinical
Dyskinesias / drug therapy
Gene Therapy
Humans
Neuroprotective Agents / therapeutic use*
Parkinson Disease / complications,  drug therapy*,  physiopathology
Small Molecule Libraries*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Neuroprotective Agents; 0/Small Molecule Libraries

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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