Most of the drugs developed to treat Alzheimer’s disease have been ineffective for years in clinical trials. Researchers at Indiana University School of Medicine recently used their rigorous pipeline to evaluate the drug’s efficacy in a failed clinical trial.
Researchers from Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD), a consortium of experts from the IU School of Medicine, The Jackson Laboratory, Sage BioNetworks, the University of Pittsburgh School of Medicine and the University of California, Irvine . recently published their study Alzheimer’s and dementia: translational research and clinical interventionA journal of the Alzheimer’s Association.
Adrian Oblak, PhD, assistant professor of radiology and imaging sciences at the IU School of Medicine and first author of the publication, said the study examined the efficacy of the drug verbestat — a beta-secretase (BACE) inhibitor — administered in the initial model-AD. Stages of Alzheimer’s disease using the Preclinical Testing Core Drug Screening Pipeline.
“Although BACE inhibitors reduced amyloid beta plaques in patients with late-stage Alzheimer’s disease during clinical trials, many of those studies were discontinued due to adverse events or lack of clinical efficacy, Oblak said. “The drug was also investigated in its effectiveness prior to the onset of Alzheimer’s disease, making it an ideal compound for the study of model-AD.”
The researchers conducted in vivo PET/MRI imaging to measure amyloid deposition and glucose uptake in the brains of animal models, measured plasma and brain amyloid beta, and assessed clinical and behavioral characteristics.
Stacy Rizzo, PhD, associate professor of neurobiology and geriatric medicine at the University of Pittsburgh Aging Institute and senior author on the paper, said the study validates the importance of the association in advancing Alzheimer’s disease research.
Rizzo said, “The Model-AD Consortium brings together experts from the fields of Alzheimer’s disease biology, mouse models, genetics, behavioral research, neuropharmacology and medical imaging to develop a research infrastructure that will support the entire Alzheimer’s research community. will benefit.” “There is currently no cure for Alzheimer’s disease and therefore there is an urgent need to find treatments and develop prevention strategies.”
The National Institute on Aging, part of the National Institutes of Health, funds the Model-AD Consortium to establish robust infrastructure for the greater research community to improve preclinical and clinical translational studies. Accelerate the pace of bringing effective and safe treatment to at-risk patients. For Alzheimer’s disease, Rizzo said.
“Under our rigorous unbiased screening strategy, we were able to prevent significant amyloid beta deposition, which was expected; however, the same dosage range that was efficacious in preventing the formation of amyloid beta plaques resulted in similar side effects in the clinic and in the absence.” were reported. cognitive improvements,” Oblak said of the study. “Therefore, we would not have prioritized this compound for progress in clinical trials had we revisited the compound using this rigorous unbiased approach.”
The results of this investigation, Oblak said, like all animal models, protocols and validation data studied by Model-AD, are increasingly made available to all researchers for preclinical drug development, thanks to the support of the NIA.
