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AI & Repurposed Drugs Offer New Hope in Alzheimer’s Fight

San Francisco, CA – Researchers are increasingly turning to existing, FDA-approved drugs and the power of artificial intelligence in the search for effective Alzheimer’s Disease (AD) treatments, moving beyond customary, and frequently enough harsh, chemotherapy-based approaches. A new study highlights promising results with the drugs letrozole and irinotecan, currently used in cancer treatment, and demonstrates the growing role of AI in accelerating drug discovery.

The need for choice therapies is critical, notably for aging populations. “We need more safe,repurposable drugs…to be tested in aged individuals with Alzheimer’s disease,” stated a researcher involved in the work.The team, a collaboration between UCSF and the Gladstone Institutes, is optimistic that adjusted dosages of letrozole and irinotecan coudl offer benefits for AD patients.Testing is currently underway using advanced mouse models.

Repurposing: A cost-Effective strategy

This approach – repurposing existing drugs – is gaining traction. Currently, roughly one-third of the 182 active Alzheimer’s clinical trials (Phases 1-4) are focused on drugs already approved for other conditions. This strategy significantly reduces costs and advancement time compared to creating entirely new medications.

AI as a “Unicorn” in Research

A key element of this latest research was the integration of artificial intelligence, specifically through the work of lead author Yaqiao Li, PhD. Li’s unique skillset – combining expertise in mouse biology, bioinformatics, single-cell RNA sequencing, and electronic health record analysis – proved invaluable. She leveraged electronic medical records to identify drugs with existing evidence of potential benefit in humans, dramatically increasing the likelihood of success.

“The really critical point was using the electronic medical record to kind of borrow clinical evidence to point us to a few drugs that seemed to show beneficial effects in humans,” Li explained. “And from there, I felt like the chance of failure was really, really low because you have all this supporting evidence already.”

Moving Towards Systemic Treatment

Researchers are now developing generative AI models that can independently formulate hypotheses and analyze clinical notes. The goal is to move beyond targeting single aspects of the disease and towards more systemic treatments that address the complex nature of Alzheimer’s.

“We are having a shift in momentum towards AI and more systems biology,” said researcher Kizil. “Backing this up with strong biology, we can get to smarter therapeutics that address a lot of different aspects of the disease rather than just one.”

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What specific inflammatory pathways are targeted by cancer immunotherapies being investigated for Alzheimer’s treatment?

cancer Drugs Offer Potential Breakthrough for Alzheimer’s Treatment

The Unexpected Link: Oncology and Neurology Converge

For decades, Alzheimer’s disease and cancer have been viewed as distinct medical challenges. However, emerging research is revealing a surprising connection, with some cancer drugs showing promise in the treatment of Alzheimer’s. This isn’t about curing cancer with Alzheimer’s treatments, but repurposing existing, well-studied oncology medications to target the underlying mechanisms of neurodegenerative diseases like Alzheimer’s.The potential impact on the millions affected by Alzheimer’s disease globally is significant.

How Cancer Therapies Target Alzheimer’s Pathology

The link isn’t random. Several key pathways implicated in cancer development also play a role in Alzheimer’s. Here’s a breakdown:

inflammation: Chronic inflammation is a hallmark of both cancer and Alzheimer’s. Certain cancer immunotherapies,designed to modulate the immune system,are being investigated for their ability to reduce neuroinflammation.

Amyloid Plaques & Tau Tangles: while traditionally viewed as solely Alzheimer’s-specific, research suggests amyloid plaques and tau tangles can trigger inflammatory responses similar to those seen in tumor microenvironments. Some targeted cancer therapies are showing potential in clearing these protein aggregates.

Growth Factors & Signaling Pathways: Dysregulation of growth factors and signaling pathways (like the PI3K/akt/mTOR pathway) is common in both diseases. Cancer drugs that inhibit these pathways are being explored for their neuroprotective effects.

Microglia Activation: Microglia, the brain’s immune cells, become chronically activated in Alzheimer’s, contributing to neurodegeneration. Certain cancer treatments can modulate microglia activity, shifting them from a pro-inflammatory to a neuroprotective state.

Specific Cancer Drugs under Examination

Several cancer medications are currently undergoing clinical trials or preclinical studies for their potential in Alzheimer’s treatment:

Bevacizumab (Avastin): Originally used to treat various cancers by inhibiting angiogenesis (blood vessel growth), bevacizumab has shown promise in reducing amyloid plaque burden in early-stage Alzheimer’s patients.The theory is that reducing blood vessel permeability in the brain can improve clearance of amyloid-beta.

Nilotinib (Tasigna): A tyrosine kinase inhibitor used in chronic myeloid leukemia (CML), nilotinib has demonstrated cognitive improvements in some Alzheimer’s patients in small clinical trials. It appears to enhance mitochondrial function and reduce tau phosphorylation.

Metformin: Commonly used for type 2 diabetes, metformin has neuroprotective properties and may reduce the risk of developing Alzheimer’s. It’s mechanism involves improving insulin sensitivity and reducing inflammation. While not strictly a cancer drug, it’s used in cancer prevention and treatment strategies.

Disulfiram (Antabuse): Used to treat alcohol dependence, disulfiram has shown potential in preclinical studies to break down amyloid plaques and protect neurons. It effectively works by enhancing autophagy, the cell’s self-cleaning process.

Immunotherapies (PD-1/PD-L1 inhibitors): drugs like pembrolizumab and nivolumab, used to boost the immune system’s ability to fight cancer, are being investigated for their potential to reduce neuroinflammation in Alzheimer’s.

Faster Development timeline: Repurposing existing drugs substantially reduces the time and cost associated with drug development, as safety profiles are already established.

Reduced Risk: These drugs have already undergone extensive safety testing in humans, minimizing potential risks for Alzheimer’s patients.

Novel Therapeutic Approach: Offers a new avenue for treating Alzheimer’s, potentially addressing the disease’s underlying pathology rather than just managing symptoms.

Cost-Effectiveness: Repurposed drugs are often more affordable than developing entirely new medications.

Not a Cure: These drugs are not a cure for Alzheimer’s, but may slow disease progression or improve cognitive function.

Individualized Treatment: The response to these drugs will likely vary depending on the individual patient and the stage of their disease.

Side Effects: All medications have potential side effects, and these