ALZHEIMER'S DISEASE

Alzheimer's disease is the most common type of dementia. Patients with Alzheimer's exhibit an irreversible, progressive neurologic disorder, resulting in loss of memory and other cognitive functions. It is the 6th leading cause of death and affects more than 5.8 million people in the United States.

Medical needs

Although there is medication that can temporarily reduce the symptoms, there is no treatment that can reverse or stop AD. Therapies that target amyloid beta, one of the hallmarks of Alzheimer's, have all failed in clinical trials. Therapies that target tau are in the early clinical development. Growing evidence suggests that abnormal cholesterol metabolism can contribute to the pathogenesis of AD. Many of the known risk factors for Alzheimer's are associated with cholesterol metabolism, such as elevated levels of plasma cholesterol and ApoE genotypes.

Mechanism of action

Although the exact mechanism of action is not known, it is demonstrated that cyclodextrin can improve cholesterol metabolism in the brain and exert neuroprotection effect in Alzheimer's disease model. HPβCD has shown encouraging results in patients with late onset Alzheimer's disease in a Phase 1 clinical trial and received IND clearance from the U.S. FDA for a Phase 2 study in December 2021. We aim to study whether RN-005 can provide a more effective and safe option than HPβCD.

References

- Cholesterol depletion inhibits the generation of β-amyloid in hippocampal neurons (PNAS, 1998)

- Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease (Journal of Experimental Medicine, 2012)

- Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice (Human Molecular Genetics, 2017)