Effect of Hydralazine on Alzheimer's Disease

It has been recently discovered that the FDA-approved drug, hydralazine, has anti-neurodegenerative efficacy based on three intriguing observations. hydralazine; 1) activates the Nrf2 pathway that controls more than 200 antioxidant proteins, 2) rejuvenates mitochondria and increases their respiration capacity and adenosine triphosphate production, 3) activates autophagy which has pathophysiological roles such as intracellular aggregate clearance. There is an emerging agreement that autophagy-lysosome defects occur early in the pathogenesis of Alzheimer's disease (AD). Nrf2 is another pathway known to be impaired in the hippocampus of AD patients who need antioxidant protection the most. Rejuvenation of mitochondria is crucial for fighting AD, as neuronal cells need more energy to afford activation of pathways such as autophagy and Nrf2. The prime objective of this application is to conduct a randomized clinical trial to assess the efficacy of hydralazine in early-stage AD patients who take one of the acetylcholinesterase inhibitor (AChEI) donepezil, rivastigmine, or galantamine.