Reversing Hypervascularization in Alzheimer’s Disease Model
University of British Columbia
Alzheimer’s disease (AD) is a well-known form of dementia. AD patients have deposits in their brains containing a protein called amyloid. Recently, we reported that amyloid causes an overproduction of blood vessels in brains of AD mouse models, and this phenomenon is also seen in AD patients. The uncontrolled sprouting of blood vessels leads to increased leakiness in the blood vessels, allowing unwanted blood products to enter the brain. Moreover, other conditions that arise due to impaired blood vessels, such as stroke and heart disease, have been implicated as risk factors for AD. Our objective is to attempt to curb the damage seen in the brains of AD model mice by treating them with drugs that limit the uncontrolled formation of new blood vessels. These drugs are already approved for use in humans, so it would be possible to move into human clinical trials if our animal trials prove successful.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
The goal of this proposal is to test whether modulation of angiogenesis, via the specific anti-angiogenic compound, Axitinib, may modify the progression of AD and function as a treatment option for AD. This drug is FDA approved for use in humans (for cancer treatment). Most excitingly, we have preliminary evidence that treatment similar drug reduces hypervascularization in a mouse model, and remarkably reduces amyloid plaques found in the brain. We would like to build on this momentum to test Axitinib. Ultimately, a choice in drugs may prove to be advantageous to patients when dealing with individual drug tolerance levels, safety, and other drug-drug interactions. Therapies for AD based on anti-angiogenics is novel and is a departure from other approaches that have thus far had limited success in treating the disease.
We have previously found that as Alzheimer’s disease progresses, there is an abnormally large number of new blood vessels that form in the brain. However, the formation of new vessels is a leaky process, which may contribute to the disease by allowing molecules that would normally be kept out of the brain to get in. Therefore the goal of this proposal is to test whether a specific anti-angiogenic compound, Axitinib, may modify the progression of AD and function as a treatment option for AD. We expect this drug to reduces hypervascularization in a mouse model, and possibly reduce the appearance of disease hallmarks such as amyloid plaques.