New drug helps protect memory in brain diseases like Alzheimer's

More than 55 million people around the world experience neurodegenerative conditions such as Alzheimer’s disease. These illnesses often compromise a person’s memory and leave them and their families feeling overwhelmed and desperate for treatment options.

Scientists at Case Western Reserve University may have uncovered a new way to maintain healthy brain function in Alzheimer’s and other related disorders.

According to Andrew Pieper, a psychiatrist and neuroscientist at University Hospitals Cleveland Medical Center, the research was focused on a lesser-studied area of the brain’s “border” instead of neurons.

Brain’s barrier may be key in memory loss

The blood-brain barrier (BBB) is a protective layer of cells that keeps out toxins and dangerous particles. It plays a crucial role in regulating which substances can pass from the bloodstream into the brain.

The team discovered that the enzyme 15-PGDH was particularly active in the BBB in mouse models of Alzheimer’s. They noticed that high levels of 15-PGDH were linked with serious damage in the brain.

The researchers tested a drug called SW033291 which blocks this enzyme and watched what happened next.

Blocking enzyme protects memory

“In these mouse models treated with the drug the BBB remained completely undamaged,” said Pieper.

He explained that the mice maintained their brain cells and showed normal memory on tests, which suggests that targeting the BBB might be more promising than only looking at amyloid, the sticky protein that is often linked with Alzheimer’s.

The team also studied a similar effect in traumatic brain injury, an event that sometimes raises the risk of future dementia. Lab mice with a concussion-like injury were given the drug a day after the trauma.

The mice did not show the usual decline in memory and movement, giving hope that BBB support could be relevant in multiple disorders.

A fresh approach to brain care

“Notably, SW033291 didn’t change how much amyloid was in the brain,” said Sanford Markowitz at Case Western Reserve and University Hospitals. He explained that this is different from recent Alzheimer’s medicines, many of which only lower amyloid in the brain.

The researchers see this enzyme-blocking strategy as a new direction for Alzheimer’s, traumatic brain injury, and possibly more conditions that involve the BBB.

This line of thinking focuses on limiting damage from within, so that the rest of the brain can keep functioning as well as possible.

Targeting amyloid may not be enough

For decades, Alzheimer’s treatments have focused mostly on removing amyloid plaques, the protein clumps often seen in patient brains.

While these plaques are associated with the disease, clearing them has not consistently improved memory or thinking ability. Some of the latest approved drugs that reduce amyloid can also cause serious side effects, like brain swelling or bleeding.

The 15-PGDH inhibitor, by contrast, does not affect amyloid levels at all, and still appears to prevent memory loss in mice.

New Alzheimer’s drug protects memory

At the moment, there are few therapies that offer meaningful relief for Alzheimer’s patients, which means that any innovation is welcomed by scientists and sufferers alike. If future clinical trials confirm these results, families dealing with memory loss may have more hope.

This concept could also spark additional interest in drugs that strengthen the blood-brain barrier. The research may ultimately open the door for simpler, safer methods to slow or stop mental decline at earlier stages.

Testing the memory drug on people

Many questions remain, including whether BBB-focused treatments can help people in advanced stages of memory loss or those with other neurodegenerative diagnoses.

It will be important to find out whether blocking 15-PGDH in humans is safe in the long-term, and how soon a therapy might become available.

Researchers aim to move the work forward by refining the drug’s design and planning more advanced animal studies. Only time will tell whether this new approach will be part of routine care for Alzheimer’s or concussion-like injuries.

Memory fix beyond Alzheimer’s

The benefits seen in individuals with traumatic brain injury suggest that 15-PGDH inhibition might help in conditions beyond Alzheimer’s.

Disorders like Parkinson’s disease, multiple sclerosis, and even long COVID may involve similar inflammation and BBB disruption.

If future studies confirm these links, SW033291 or similar drugs could play a role in treating a range of brain disorders – not by targeting disease symptoms directly, but by keeping the brain’s defense system intact.

The study is published in the Proceedings of the National Academy of Sciences.

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