A class of compounds that can prevent degeneration of neurons, the underlying cause of conditions like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), has been identified by US researchers.
Researchers at the University of Texas at Dallas and Southern Methodist University insist that their study attains significance because current medications for such neurodegenerative diseases alleviate only their symptoms but not the underlying cause.
The researchers describe the compounds they have identified as 3-substituted indolones.
They have also conducted a structure-activity relationship study to identify substituent groups that are important for neuroprotective efficacy.
A previous study by the same group showed that one of these 3-substituted indolones, called GW5074, prevents neurodegeneration and improves behavioural outcome in a mouse model of neurodegeneration.
Dr. Santosh D'Mello, the study's senior author, said: "More recent but unpublished work by our group and Doris Kretzschmar, a collaborator at the Oregon Health and Science University, found that GW5074 and other related 3-substituted indolones are also protective in a fly model of Alzheimer's disease."
The current study has unveiled several compounds that are more efficacious than GW5074, and that do not display any cytotoxicity even when used at high doses.
Thus, say the researchers, these 3-substituted indolones are thus novel and promising candidate therapeutic agents for pre-clinical testing against human neurodegenerative conditions.
Dr. D'Mello said: "Studies into the mechanisms underlying neuronal apoptosis has identified several molecules that can be targeted in developing drugs to treat neurodegenerative diseases. Some of these have been tested in human clinical studies but have not proven to be effective at reducing neurodegeneration in patients. Our study has identified some 3-substituted indolones that might be suitable for development as therapeutic agents.
The structure-activity relationship analysis we have described in our report, although not exhaustive, also provides useful information on which other efficacious 3-substituted indolones can be synthesized and tested in pre-clinical and clinical studies".
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said: "The work by D'Mello and colleagues has provided the basis for testing new versions of 3-substituted indolones for efficacy in the treatment of Alzheimer's disease and other neurodegenerative disorders. These drugs provide promising new therapeutic approaches to deal with the underlying cause of these disorders: neuronal cell death."