drugs organ transplant alzheimers

Drugs Used in Organ Transplants Might Delay Alzheimer’s

By | March 27th, 2018

As scientists continue to search for a cure for Alzheimer’s, a study from University of Texas Southwestern suggests that a drug might already exist that could at least slow down the progression of the disease. Researchers found that anti-rejection drugs used after an organ transplant to suppress the immune system’s response were able to rescue parts of the brain that are lost to Alzheimer’s in an experiment on mice.

In Alzheimer’s disease, neurons stop functioning correctly, and eventually stop communicating with each other, before dying off. Scientists believe that problems with memory and changes in behavior, the hallmark symptoms of the disease, start when neurons stop communicating with each other.

The synapses that facilitate communication between neurons have tiny branches like trees that are called dendritric spines, said Dr. James Malter, Chairman of Pathology and corresponding author of the study. When these spines are lost in a disease like Alzheimer’s, functions like language, spatial reasoning, conscious thinking, sight, hearing, and other senses are affected.

In this study, researchers were able to track the process that leads to the loss of the dendritic spines.

“We found that beta-amyloid, which is overproduced in the brains of most people with Alzheimer’s, turns on a protein called calcineurin. Activated calcineurin then causes the inhibition of a second protein called Pin1, leading to loss of dendritic spines and synapses,” said Malter.

That’s where a drug that’s already approved for organ transplants comes in. Malter’s team carried out experiments that showed extra doses of Pin1 or exposure to a drug called FK506—the organ transplant drug that blocks calcineurin—stopped the brain from losing synapses. When scientists measured dendritic spine density after exposure to FK506, they found that it increased.

These results echo conclusions published in an earlier study, which found that patients who were given FK506 after a transplant developed Alzheimer’s less frequently than was typical of the rest of the population.

Some form FK506 has been approved since 1983. If scientists find that it does slow down the beginning stages of Alzheimer’s in follow-up experiments, patients could get their hands on the drug a lot faster than the typical wait time for drug approval process.

“As an FDA-approved drug, we propose that FK506 be evaluated through clinical trials as a treatment for early-stage Alzheimer’s disease,” said Malter. “Anti-rejection drugs given to organ transplant recipients work by suppressing the immune system and, as a result, can increase the risk of infection. Our experiments suggest that lower doses of FK506 than are needed to block transplant rejection may be able to protect neurons from beta-amyloid without significant immunosuppression.”

This study was published in the journal Science Signaling.


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