Lines of therapeutics research in Alzheimer's disease.
Therapeutic research is being stepped up to light Alzheimer's disease (AD), although its heterogeneity, the insufficiency of physiopathological knowledge, and the lack of a reference treatment impede the development of a drug to combat it. However, progress has opened up many avenues. Some recent approaches that have led to therapeutic research are identification of biochemical abnormalities, identification of dysfunction in several neurotransmitter systems (cholinergic, catecholaminergic, serotonergic, and peptidergic systems), and the study of senile plaques and neurofibrillary degeneration tangles. Although some types of therapy have been used for a long time (e.g., metabolic products such as nootropes), recently developed drugs target different systems: for example, neurotransmitter systems are important for symptomatic improvements in cognitive functions. The principal improvements expected with some new anticholinesterases whose role is to increase the available amount of central acetylcholine are in memory and attention. Second, retarding neuronal degeneration by acting on amyloid plaques is another possible future therapy. Here, protease inhibitors appear to be interesting tools. Third, the endototoxin etiology of neurodegenerative illnesses remains uncertain. After the first attempts with N-methyl-D-aspartate (NMDA) antagonists that had inescapable side effects, hopes rose with some new pharmacological tools such as the AMPA/kainate antagonists. Fourth, a possible stimulation of neuronal plasticity by neurotrophic factors such as nerve growth factor (NGF) constitutes another prospected research area. Fifth, the inflammatory aspects of degenerative diseases attract the attention of many laboratories and preliminary reports are hopeful. Finally, out of the established pharmacological tools, gene therapy, though still hypothetical, may become the expected treatment in the future. Pharmacotherapy used in the most common types of dementia has until now been largely palliative and dealt with symptoms. It is nonetheless not unreasonable to look forward to the development of drugs that will be able to combat the evolution of the dementia itself, rather than its symptoms. A list of different products developed to treat AD is concluded by an evaluation of the expected results and, in particular, the orientations likely to be necessary.
Shvaloff
A
A
Division Thérapeutique de Médécine Appliquée, Institut de Recherche Internationales Servier, Courbevoie, France.
Neuman
E
E
Guez
D
D
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D006801:Humans; D018697:Nootropic Agents / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018697:Nootropic Agents