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.
Phase:
Phase 3
Details
Lead Sponsor:
Shahid Sadoughi University of Medical Sciences and Health Services
Collaborators:
McMaster University National Institute for Medical Research Development (NIMAD), Iran