Alzheimer's Disease

Alzheimer’s disease is the most common form of dementia. It is generally diagnosed in people over 65 although early onset disease can occur much earlier. It affects over 37 million people worldwide. There is an incidence of five to eight per thousand which represents half of the new dementia cases each year. Advancing age is the primary risk factor for the disease. The disease has no cure and is fatal. It progresses through multiple stages, initially signified by memory loss and cognitive decline followed by mood swings, irritability and finally shut down of bodily functions. Current treatments offer mild symptomatic relief and do not prolong life. There is no known disease altering treatment.

AD is characterized pathologically by the presence of plaques composed of aggregated Ab (39-43 amino acid peptide of b-amyloid), neurofibrillary tangles (NFTs) and neurotic plaques composed of hyper-phosphorylated tau. The presence of both plaque and NFTs is required for the diagnosis of AD, and the amounts of each correlate with a degree of dementia.  Tau hyperphosphorylation is regulated by a series of protein kinases.  Inhibition of GSK3b, a kinase shown to phosphorylate tau, has been shown to minimize the motor deficits typically observed in a tau transgenic mouse model. Zenobia is targeting a related kinase.

We have completed the crystal structure for this kinase and identified inhibitors.  We are in the process of screening our full fragment library.