New Method to Stop Alzheimer's Disease Progression Discovered by Scientists

Scientists at the University of Colorado Anschutz Medical Campus have discovered a new potential treatment strategy for Alzheimer's disease. The research team found that using a drug, called nutlin, to inhibit a protein known as Mdm2 stops the destruction of synapses commonly linked to Alzheimer's. This approach deviates from the usual methods that aim to eliminate amyloid plaque and may be able to stop the progression of the disease. Further testing in animal models is planned.

The researchers have identified that blocking a key protein can prevent the common synapses and dendritic spines damage associated with Alzheimer's disease.

The research, led by Tyler Martinez, a Ph.D. student in Pharmacology and Molecular Medicine at the University of Colorado School of Medicine, was recently published in the eNeuro journal.

The team used rodent neurons in their research and discovered that the experimental cancer drug nutlin, which targets the Mdm2 protein, successfully halted the excessive pruning of synapses caused by neurotoxic amyloid-b peptides in Alzheimer's disease.

Professor Mark Dell’Acqua, PhD, the senior author of the study and vice-chair of the Department of Pharmacology at the CU School of Medicine, explained that dendritic spine synapses, which are linked to cognitive impairments in Alzheimer's, are usually trimmed in the post-natal brain, but Alzheimer's accelerates this process leading to memory and learning loss.

According to Dell’Acqua, Mdm2 protein intensifies the pruning of synapses when amyloid-b is present. However, this process was completely blocked when nutlin was applied to neurons. Therefore, inhibiting the Mdm2 protein could be an effective treatment approach.

While most Alzheimer's research focuses on eliminating amyloid plaque in the brain, Dell’Acqua questions whether this is the optimal treatment strategy. He suggests interfering in the process by curtailing the impacts of amyloid-b could be another approach. This interference could occur by targeting Mdm2.

The scientists are now working to determine whether they can prevent the progression of Alzheimer's in an animal model. If successful, this could lead to future human trials. Notably, drugs targeting Mdm2 are already in clinical trials for cancer, but FDA approval is still required.

Dell’Acqua described the findings as an “encouraging first step” towards finding a new treatment for Alzheimer’s.