Could cancer drugs be the future of Alzheimer’s treatment?

With few treatments available to stop or reverse Alzheimer’s disease, scientists have turned to cancer drugs as a potential means of resuming cognitive decline.

Alzheimer’s cases are increasing in the United States and the world due to an aging population, but there is no remedy for the disease. Try to develop new treatments that slow down the progress of the disease, rather than reducing symptoms, have frequently failed.

Only two drugs – therapies on the Leqembi and Kisunla antibodies – are currently approved by the Food and Drug Administration to slow down the progression of Alzheimer’s disease, and scientists say that their advantages are limited.

Some pharmaceutical companies have stopped or abandoned Their Alzheimer’s drug development programs due to unsuccessful trials. Others try to use existing drugs, especially Popular weight loss drugsTo fight Alzheimer’s disease.

In this spirit, researchers from the University of California in San Francisco have carried out a wide search for drugs that could be reused to treat the disease – in theory, reducing the time when drugs could be made available to patients. They have traveled a database of more than 1,300 drugs from various classes, including antipsychotics, antibiotics, antifungals and chemotherapy medications. Then they examined how these drugs affected the expression of genes.

Their new study, Published Monday In the review cell, identified two cancer drugs Like the best candidates to reduce the risk of Alzheimer’s in patients. When combined, drugs seemed to slow down or reverse the symptoms of Alzheimer’s in mice. One of the drugs is normally used to treat breast cancer, while the other is effective against colon and lung cancer.

Alzheimer’s disease is associated with significant changes in the way the genes are expressed in the brain, leading to the increase in the production of certain proteins and to the decrease in the production of others. These imbalances can disrupt brain functioning and contribute to symptoms such as memory loss.

Less than 90 drugs in researchers The database has reversed the expression of the genes linked to Alzheimer’s in human brain cells. And five drugs in particular seemed to reduce the risk of Alzheimer’s in real patients, based on electronic medical records. The authors finally selected two of these drugs, both approved by the FDA to treat cancer, to test in mice.

“We did not expect the drugs against cancer to arise” as the most promising, said Marina Sirota, co-author of the study and interim director of the UCSF Bakar Computational Health Sciences Institute.

The authors said that the medication against breast cancer seemed to change the expression of genes in nerve cells. And the colonist and lung cancer Iriotencan seemed to change the expression of genes in glial cells, which support the nervous system. Alzheimer’s can destroy nerve cells and cause a proliferation of glial cells, creating inflammation in the brain.

In A 2020 studyPatients with breast cancer who received letrozole were less likely to develop Alzheimer’s disease than patients who have not received the medication. The colorectal cancer survivors treated by the irinotecan also had a reduction in the risk of Alzheimer’s, according to A 2021 study.

After testing the drugs in mice, the study authors found that the two -medication combo reversed cerebral degeneration and improved memory in mice which had developed Alzheimer’s characteristics as aged.

Because mice results often do not translate into humans, researchers hope to test drugs in a clinical trial with Alzheimer’s patients.

“The development of a new drug can take hundreds of millions, even billions of dollars, to take an average of more than 10 years. For this reused drug, it is generally only two or three years, and you can then go to the clinical trial and the cost is much, much lower, “said Dr. Yadong Huang, a study author and the neurology teacher at the UCSF.

“We have still not generated or produced very effective drugs that can really slow cognitive decline considerably,” he added.

Part of the difficulty of developing drugs for Alzheimer’s disease is the complexity of the disease. Its exact cause is largely unknown.

For the moment, the authors have said, we don’t know exactly why cancer drugs seem to work against Alzheimer’s disease. A theory is that breast cancer blocks the production of estrogen, a hormone which controls the expression of a large number of genes. The medicine against colon and lung cancer can also block inflammation in the brain by preventing the proliferation of glial cells – although Huang has declared that there are other possibilities.

Dr. Melanie McREYNOLDS, assistant professor of biochemistry at the Pennsylvania State University, who was not involved in the study, offered another theory.

Her research suggested that a different type of cancer medication could help treat Alzheimer’s disease by regulating glucose metabolism, the process by which cells make energy. McREYNOLDS said the process is necessary for various brain cells to communicate with each other.

“With aging, with stress, with illnesses, this communication line is disturbed,” she said.

McREYNOLDS said the combo of medicines tested in the new study could reverse the metabolic decline – which it called “the secret to having contributed to better results with Alzheimer”.

But assess how Alzheimer’s patients tolerate the combination of cancer drugs. The letrozole can cause hot flashes and the irinotecan can cause severe diarrhea. Both drugs can cause nausea and vomiting.

“These drugs have enormous side effects, so you should always balance and determine whether these types of side effects would occur for someone with Alzheimer,” said Sirota. “It is not that it is a slam dunk.”