Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Experimental Drug Reverses Cognitive Impairment in Aged Alzheimer's Disease Mice

By BiotechDaily International staff writers
Posted on 29 May 2013
Image: Senior author Dr. Dave Schubert (Photo courtesy of the Salk Institute for Biological Studies).
Image: Senior author Dr. Dave Schubert (Photo courtesy of the Salk Institute for Biological Studies).
Image: First author Dr. Marguerite Prior holding ampoule of the J147 drug (Photo courtesy of the Salk Institute for Biological Studies).
Image: First author Dr. Marguerite Prior holding ampoule of the J147 drug (Photo courtesy of the Salk Institute for Biological Studies).
Image: Salk Institute scientists developed J147, a synthetic drug shown to improve memory and prevent brain damage in mice with Alzheimer's disease (Photo courtesy of the Salk Institute for Biological Studies).
Image: Salk Institute scientists developed J147, a synthetic drug shown to improve memory and prevent brain damage in mice with Alzheimer's disease (Photo courtesy of the Salk Institute for Biological Studies).
An experimental drug for treatment of Alzheimer's disease (AD) gave excellent results in a mouse model of the disease and is expected to be tested in clinical trials leading to its eventual use in humans.

The drug, J147, is an orally bioavailable, blood brain-barrier permeable benzylidine-acetohydrazide compound proven safe in mice that was developed by researchers at the Salk Institute for Biological Studies (La Jolla, CA, USA). The potential of J147 for treatment of AD was discovered during a screening process using cultured neurons, a system that mimicked the brain of a patient with advanced AD.

In the current study, Salk Institute investigators treated aged AD mice with J147. Cognitive behavioral assays, histology, ELISA, and Western blotting were used to assay the effect of J147 on memory, amyloid metabolism, and neuroprotective pathways. J147 was also investigated in a scopolamine-induced model of memory impairment and compared to the drug donepezil, the most widely prescribed compound for treatment of AD.

Results published in the May 14, 2013, online edition of the journal Alzheimer's Research and Therapy revealed that J147 had the ability to rescue cognitive deficits when administered at a late stage in the disease. The ability of J147 to improve memory in aged AD mice was correlated with its induction of the neurotrophic factors NGF (nerve growth factor) and BDNF (brain derived neurotrophic factor) as well as several BDNF-responsive proteins that are important for learning and memory.

The comparison between J147 and donepezil in the scopolamine model showed that while both compounds were comparable at rescuing short term memory, J147 was superior at rescuing spatial memory and a combination of the two worked best for contextual and cued memory.

"Alzheimer's disease research has traditionally focused on a single target, the amyloid pathway," said senior author Dr. Dave Schubert, professor of cellular neurobiology at the Salk Institute for Biological Studies, "but unfortunately drugs that have been developed through this pathway have not been successful in clinical trials. Our approach is based on the pathologies associated with old age - the greatest risk factor for Alzheimer's and other neurodegenerative diseases - rather than only the specificities of the disease."

"In addition to yielding an exceptionally promising therapeutic, both the strategy of using mice with existing disease and the drug discovery process based upon aging are what make the study interesting and exciting," said Dr. Schubert, "because it more closely resembles what happens in humans, who have advanced pathology when diagnosis occurs and treatment begins. Most studies test drugs before pathology is present, which is preventive rather than therapeutic and may be the reason drugs do not transfer from animal studies to humans."

Related Links:

Salk Institute for Biological Studies




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: This novel, flexible film that can react to light is a promising step toward an artificial retina (Photo courtesy of the American Chemical Society).

Novel Nanofilm May Be Artificial Retina Precursor

Researchers have used advanced nanotechnology techniques to develop a light-sensitive film that has potential for future artificial retina applications. Investigators at the Hebrew University of Jerusalem... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

R&D Partnership Initiated to Reduce Development Time for New Drugs

nanoPET Pharma, GmbH (Berlin, Germany) signed an open-ended framework contract with the international pharmaceutical company Boehringer Ingelheim (Ridgefield, CT, USA). By developing customized contrast agents for research in both basic and preclinical studies, nanoPET Pharma will contribute to the enhancement of Boehringer... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.