CLEVELAND — A Cleveland-led team from University Hospitals, Case Western Reserve University and the Louis Stokes VA has identified a protein that appears to act as a gatekeeper for brain aging, offering a potential new target to slow age-related memory and thinking problems.
The research, published in the journal PNAS, focuses on the blood-brain barrier, the tightly regulated “shield” of blood vessel cells that keeps toxins out, clears waste and directs blood flow to busy areas of the brain. In preclinical models, scientists found that a protein called KLF4 helps maintain this barrier; when levels of KLF4 drop in those blood vessel cells, the barrier begins to leak, small vessels are lost and the brain becomes more vulnerable to inflammation and damage.
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When researchers deliberately reduced KLF4 in middle-aged mice, the animals showed earlier-than-expected signs of brain aging: oxidative injury, neuroinflammation, nerve cell damage, anxiety-like behavior and cognitive decline typically seen only in much older animals. The team now views KLF4 as a promising therapeutic target, with future drugs potentially aimed at preserving or restoring its function to protect the blood-brain barrier and, in turn, memory and thinking.
Medicare’s AI Pilot Creates New Hurdles for Patients
A new Medicare pilot program meant to crack down on wasteful care is drawing complaints from patients and clinicians in six states, including Ohio. The Wasteful and Inappropriate Service Reduction (WISeR) model adds prior authorization requirements to 13 services in traditional Medicare that federal officials say are prone to fraud or overuse, such as certain skin substitutes, spinal injections and procedures for spinal fractures.
The program relies on artificial intelligence to rapidly review electronic requests from doctors’ offices, with officials saying most appropriate requests should be approved within 72 hours and that the goal is to reduce unnecessary care without delaying needed treatment. But doctors, hospital leaders and patients interviewed by KFF Health News report confusion, denials they view as erroneous, long waits and delayed payments since the rollout in January. Some health systems have documented sizable backlogs for procedures like epidural injections, and several clinicians say they are seeing weeks-long delays in payment despite rules that clean claims should be paid in 15 days.
Technology vendors say humans make the final call on approvals, but clinicians worry AI systems are driving some denials, occasionally misreading or mischaracterizing information in charts. Federal officials acknowledge that only a small percentage of providers commit fraud and that they are monitoring the program and adjusting operations, even as many patients and doctors in the pilot states feel they are now facing the same red tape that has long frustrated people with private insurance.
1940s Drug Sheds New Light on Polycystic Kidney Disease
In more hopeful news for people living with polycystic kidney disease (PKD), Mayo Clinic researchers have uncovered a previously unrecognized way the kidneys manage water — using a 1940s-era drug as a scientific clue. PKD is a common inherited disorder that causes fluid-filled cysts to grow in the kidneys, affecting millions worldwide and an estimated 140,000 people in the U.S. with the most common form; many eventually need dialysis or a kidney transplant.
The new study, published in the Journal of Clinical Investigation, shows that beyond the well-known vasopressin hormone pathway, kidney cells can use a urate-related signaling route to move water channels to the cell surface and concentrate urine. Researchers discovered this while testing probenecid — a drug originally used to help conserve penicillin — in lab models; instead of worsening cyst growth as expected, the drug slowed it.
In preclinical work and a small clinical trial, adding probenecid to the only approved PKD drug, tolvaptan, cut patients’ daily urine volume by about 30% and reduced nighttime bathroom trips, while maintaining the treatment’s benefit against cyst growth. Because probenecid is older, affects multiple systems and is not widely used today, the team does not plan to rely on it long term but is using what it revealed about this alternate pathway to design more precise therapies that could preserve kidney function with fewer side effects.
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