Genes to Therapy / Stem Cell Screening

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The goal of Genes to Therapies is the development of effective interventions at various points in the pathological cascade of Alzheimer’s disease.

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Of the Alzheimer’s genes and candidate genes that have been identified, more than 60 are being screened for mutations/functional variants in the Whole Genome Sequencing project. Of these, more than 20 variants have been prioritized for thorough investigation based on three important criteria:

• High genetic impact or ranking in Alzheimer’s pathology
• “Druggable,” as defined by being known in biological systems and producing proteins as those that appear to be most readily accessed and modified by typically successful therapeutic agents, such as small molecules or biologicals
• Affect the most obvious intervention points, which include Abeta/plaque production and clearance, tangle formation/spreading, and neuroinflammation.

Stem cells are the generic “raw materials” an adult human body transforms and uses to repair and replenish its various kinds of tissue. Because these cells are undifferentiated, they can be treated with a defined cocktail of factors in a set sequence to cause maturation of cells into discrete cell types. With a tool called induced pluripotent stem cells (iPS cells), it now is possible to take skin cells from adults and return them to this immature state. By redirecting skin cells from Alzheimer’s patients and turning them into nerve cells, we are able to study adult Alzheimer’s neurons (nerve cells) in the lab. These Alzheimer’s neurons can be studied either in a dish or by transplanting them into the brains of host mice.

Researchers funded by our organization developed, studied, and maintained Alzheimer’s neurons that are be used to screen for new drugs. This Stem Cell Bank is available for use by researchers around the world to accelerate drug screening. The initial targets for such screening are drugs that already have been proven safe in humans. Other targets include compounds developed specifically to interrupt Alzheimer’s pathology. New drugs may be based on information derived from the study of these human Alzheimer’s neurons.