New Delhi: A study published on Thursday found that standard hormone therapy treatment for prostate cancer may increase the risk of Alzheimer’s disease in men with cancer, potentially informing future research and medical practice in this area.
Androgen deprivation therapy (ADT) is a treatment for prostate cancer. It decreases testosterone, the most common androgen the cancer requires to grow.
However, as the medication removes androgen, a crucial regulator of amyloid metabolism, more amyloid is left to build the plaques associated with Alzheimer’s. Amyloid metabolism is the process by which amyloid, a protein that can accumulate in the brain, is produced and broken down. This accumulation is a key feature of Alzheimer’s disease, according to researchers from the Medical College of Georgia at Augusta University in the United States.
“We know that prostate cancer itself also largely affects men over age 65, which is a population that’s already at a higher risk of Alzheimer’s, simply due to their age,” said Qin Wang, director of the Programme for Alzheimer’s Therapeutic Discovery at MCG.
However, she said in the paper published in Science Advances that the role of ADT “is not largely understood.”
To understand the link, the team created an animal model with Alzheimer’s disease and cancer. The team then delivered the ADT for eight weeks while monitoring androgen levels, tumour size, and changes in the blood to look for immune markers.
Next, the team developed other animal models — a so-called wild type (without Alzheimer’s or cancer), a group with just Alzheimer’s, and a group with just cancer that received ADT therapy.
While there wasn’t any “significant difference in the plaque load” at the end of eight weeks, they did find hyperactivity in “glial cells (that are part of the central nervous system) of the groups with just cancer and the groups treated with ADT”.
This indicated inflammation in the brain, Wang said.
Further, they found an increase in pro-inflammatory cytokines—small proteins that trigger an increase in inflammation—and a decrease in anti-inflammatory cytokines. This was notably declined in the animals with Alzheimer’s and cancer who received ADT.
Importantly, the animals’ blood-brain barrier, a protective barrier that regulates the passage of substances from the blood into the brain, showed significant damage. “The ADT treatment is actually making the blood-brain barrier more permeable. This increased permeability would explain why there is so much more inflammation in that group,” Wang said.
Using a combination of ADT and natalizumab — a drug used to treat multiple sclerosis and Crohn’s disease — the team also treated the mice who had cancer and those with Alzheimer’s and cancer.
The treatment reduced the infiltration and subsequently improved the integrity of the blood-brain barrier. The pro-inflammatory cycle was also reduced, while the cognitive function improved, offering a ray of hope for future treatment possibilities.
“We now know that it’s not just about the amyloid plaques. The immune system’s response is the contributing factor here,” Wang said, emphasising the urgent need for clinical trials in patients who are undergoing ADT for prostate cancer.
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–IANS
