Human Stem-Cell Based Development of a Potent Alzheimer’s Drug Candidate

Over 6 million people in the US suffer from Alzheimer’s disease (AD). There are no drugs that prevent the death of nerve cells in AD, nor has any drug been identified that can stimulate nerve cell replacement in aged human brain. Importantly, even if nerve cells could be replaced, the toxic environment of the AD brain which caused the disease in the first place will likely kill any cells that are born into that environment unless they are resistant to those conditions or can be protected by a drug. Therefore, drugs that stimulate the generation of new neurons (neurogenesis) alone will not be effective. A drug with both neurogenic and neuroprotective properties is required. With the ability to use cells derived from human neural precursor cells (hNPCs) derived from human embryonic stem cells (hESCs) as a screen for neurogenic compounds and with CIRM support, we have made a drug candidate that is both neuroprotective and neurogenic for therapeutic use in AD. To get this drug candidate, called CAD-031, into clinical trials for AD, it needs to pass a number of tests before the FDA required studies are initiated. The goal of this grant is to carry out these tests, and to date, CAD-031 has done exceptionally well in all of them. During year one of this grant, we have completed a large-scale drug synthesis, the drug metabolites from human, dog, rat, and mouse liver cells were identified and screened for biological activity and safety. Formulation and pharmacological studies were completed and the drug metabolites identified in blood and brain. A number of safety screens have been completed to determine if there is any toxicology issue that could derail the candidate. To date, there are none. We have started studies that will determine how the drug is working and animal testing in mouse models of AD. This work will optimize the chances for the true therapeutic potential of this very first stem cell based drug candidate for AD.