### Exploring Real-World Evidence to Validate Alzheimer’s Therapeutic Efficacy
Alzheimer’s disease is a complex condition that affects millions of people worldwide. Finding effective treatments has been a long-standing challenge in the medical field. Recently, researchers have been exploring a new approach to validate the efficacy of potential Alzheimer’s treatments by using real-world evidence. This method involves analyzing data from existing electronic health records and databases to see if certain drugs already approved by the FDA might also help with Alzheimer’s.
#### The Bumetanide Discovery
One such discovery involves a drug called bumetanide. For over 30 years, bumetanide has been used to treat conditions like hypertension and heart failure by helping the body get rid of excess fluids. Researchers at the Gladstone Institutes, in collaboration with scientists from UC San Francisco and Icahn School of Medicine at Mount Sinai, found that bumetanide not only reverses signs of Alzheimer’s disease in mice but also in human brain cells. They analyzed electronic health records from two independent institutions and discovered that people over 65 who took bumetanide were less likely to develop Alzheimer’s disease compared to those who didn’t.
This is significant because bumetanide already has a well-established safety record. This means that if clinical trials confirm its efficacy, it could reach patients much faster than typical drug development processes. The researchers are now planning to move bumetanide towards human clinical trials for treating Alzheimer’s disease, starting with people who carry the APOE4 gene, which is a known risk factor for the disease[2].
#### Repurposing Existing Drugs
The approach of repurposing existing drugs is not new but has gained momentum in recent years. By leveraging real-world data, researchers can quickly test what these drugs might achieve in treating complex diseases like Alzheimer’s. This method is efficient because it avoids the need for extensive animal and cell studies followed by in-depth safety testing before launching clinical trials in humans.
For instance, the researchers evaluated two large electronic health record databases—one from UCSF and another from Mount Sinai Health System. They compared patients over 65 who took bumetanide with those who took different diuretic drugs. The results showed that patients who took bumetanide were 35 to 75 percent less likely to be diagnosed with Alzheimer’s disease. This suggests that bumetanide might work more broadly against Alzheimer’s disease, beyond just those who carry the APOE4 gene[2].
#### Other Research Efforts
While the discovery of bumetanide is promising, other research efforts are also underway to find effective treatments for Alzheimer’s. For example, scientists are studying how certain genetic risk factors contribute to the disease. The multifunctional mitochondrial enzyme Scully (Scu)/HSD1710 is linked to Alzheimer’s because it binds to A peptides and is overexpressed in the postmortem brains of AD patients. Researchers have found that Scu-deficient flies exhibit inhibitory control deficits and memory loss in an aging-dependent manner, suggesting its role in dementia[3].
Additionally, researchers are developing new tools to detect and study tau protein aggregates, which are a defining characteristic of Alzheimer’s disease. The tau Seed Amplification Assay (Tau-SAA) can accurately detect tau pathological aggregates in patients’ samples and has potential as a drug screening platform for therapeutics targeting tau spreading in AD[3].
#### Conclusion
Exploring real-world evidence to validate Alzheimer’s therapeutic efficacy is a promising approach. By repurposing existing drugs like bumetanide, researchers can potentially find effective treatments faster. This method combines computational drug repurposing with precision medicine, leveraging existing sets of experimental and real-world data for rapid preliminary validation. While more research is needed, these discoveries offer hope for those affected by Alzheimer’s disease.
In summary, the journey to find effective treatments for Alzheimer’s is ongoing, but the use of real-world evidence is providing new insights and potential solutions
