Alzheimer’s disease Therapeutics Strategies:
Did you know that there are currently over one hundred therapeutics in development for the treatment of Alzheimer’s disease? They can generally be sorted into several common therapeutic strategies. Some of the approaches developed to address them are listed below.
Metabolic: Metabolism is a process through which the brain can perform chemical reactions to produce energy, and rid itself of unwanted waste and toxins. A malfunctioning brain metabolism can result in a lack of energy, and a buildup of waste products and toxins in the brain. Patients with Alzheimer’s often exhibit altered or reduced brain metabolisms, which may be responsible for some Alzheimer’s symptoms. Alzheimer’s therapeutics targeting metabolism attempt to promote or re-start healthy brain metabolic functions and reduce the buildup of unwanted materials in the brain. Our lab is currently developing intranasal insulin as a metabolic therapy for Alzheimer’s disease. Human trials of intranasal insulin have shown that it has improved memory and functioning in patients with Alzheimer’s disease or Mild Cognitive Impairment.This treatment has also been shown to improve memory in normal healthy adults.
Inflammation: Inflammation is a type of defense mechanism used by the brain to protect itself against infection, toxins, and tissue damage. When inflammation occurs for too long, it can cause lasting damage and brain cell death. Elevated inflammation is commonly associated with Alzheimer’s disease, and may be responsible for some Alzheimer’s symptoms. Alzheimer’s therapeutics targeting inflammation attempt to reduce long term inflammation in the brain to alleviate the damage it can cause. Our lab is currently developing an intranasal formulation of deferoxamine, a drug normally used to treat iron overload, to combat the brain inflammation associated with Alzheimer’s disease. We have shown that intranasal deferoxamine improves memory in normal mice and reduces memory loss in a mouse model of Alzheimer’s disease. This treatment is also effective in animal models of Parkinson’s disease and stroke.
Amyloid-Related: Amyloid Beta is a misfolded version of a protein found in the brain. Amyloid beta is toxic to the nerve cells that make up the brain, and can clump together into structures called plaques, which are common in the brains of patients with Alzheimer’s. Therapeutics targeting amyloid beta typically focus on preventing its formation or removing it from the brain.
Cholesterol: Cholesterol is a fat-like molecule found in human cells, and in many foods. Elevated levels of unhealthy cholesterols are often associated with increased risk for heart disease and stroke, but have also been shown to increase a person’s risk for Alzheimer’s disease. High cholesterol levels are associated with higher levels of amyloid beta, a toxic protein characteristic of Alzheimer’s disease. Alzheimer’s therapeutics targeting cholesterol focus on reducing blood and brain cholesterol levels.
Cholinergic System: The cholinergic system is a pathway in the brain that uses acetylcholine, a brain signal molecule, to communicate. Acetylcholine signaling is an important part of learning and memory, and is often reduced in patients with Alzheimer’s. Alzheimer’s therapeutics targeting the cholinergic system attempt to increase the amount of acetylcholine signaling in the brain by working against the processes that normally remove it. Aricept™,Exelon™, and Razadyne are all examples of Cholinergic system-targeting therapeutics.
Other Neurotransmitters: Neurotransmitters are molecules the brains uses to communicate. Patients with Alzheimer’s often have disrupted levels of several important neurotransmitters including norepinephrine, glutamate, serotonin, and many more. Therapeutics targeting other neurotransmitters aim to readjust their concentrations to healthy levels and restore healthy brain function. Namenda™ is a commonly prescribed neurotransmitter-targeted therapeutic.
Tau: Tau is a protein that occurs normally in healthy brains. In patients with Alzheimer’s disease, tau malfunctions and forms together into long fibers called tangles. These tangles disrupt the function of brain cells and continue to grow until they break and kill the cells. Therapeutics targeting tau aim to prevent the formation of tangles, and to remove existing tangles to preserve brain function.
Other: Alzheimer’s disease has a wide range of symptoms and potential underlying causes. Numerous therapeutics are being developed to increase protective brain growth factors, correct the various nutrient deficiencies, malfunctioning brain chemicals, genetic risk factors, and various symptoms associated with Alzheimer’s disease.