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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.

Unmet 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. the APOE4 gene is a variant of the apolipoprotein E (APOE) gene, which is involved in cholesterol metabolism. Individuals with the APOE4 gene have up to a 15-fold increased risk of developing AD and more than 50% of AD patients possess the APOE4 gene. While cholesterol metabolism is a promising and novel target for treating AD, there is no treatment.

Mechanism of action

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Targeting brain cholesterol metabolism holds the potential to be a disease-modifying therapeutic approach. It is demonstrated that cholesterol metabolism modulators (CMMs) 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 are investigating whether Renatus' proprietary CMMs can provide a more effective modality in regulating brain cholesterol metabolism.

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)

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