Alzheimer’s treatments: What’s on the horizon?
Despite many promising leads, new treatments for Alzheimer’s are slow to emerge.
Current Alzheimer’s treatments temporarily improve symptoms of memory loss and problems with thinking and reasoning.
These Alzheimer’s treatments boost the performance of chemicals in the brain that carry information from one brain cell to another. They include cholinesterase inhibitors and the medicine memantine (Namenda). However, these treatments don’t stop the underlying decline and death of brain cells. As more cells die, Alzheimer’s disease continues to progress.
Experts are cautious but hopeful about developing treatments that can stop or delay the progression of Alzheimer’s. Experts continue to better understand how the disease changes the brain. This has led to the research of potential Alzheimer’s treatments that may affect the disease process.
Future Alzheimer’s treatments may include a combination of medicines. This is similar to treatments for many cancers or HIV/AIDS that include more than one medicine.
These are some of the strategies currently being studied.
Taking aim at plaques
Some of the new Alzheimer’s treatments target clumps of the protein beta-amyloid, known as plaques, in the brain. Plaques are a characteristic sign of Alzheimer’s disease.
Strategies aimed at beta-amyloid include:
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Recruiting the immune system. Medicines known as monoclonal antibodies may prevent beta-amyloid from clumping into plaques. They also may remove beta-amyloid plaques that have formed. They do this by helping the body clear them from the brain. These medicines mimic the antibodies your body naturally produces as part of your immune system’s response to foreign invaders or vaccines.
In June 2021, the U.S. Food and Drug Association (FDA) approved the monoclonal antibody aducanumab (Aduhelm) for the treatment of Alzheimer’s disease in some people. The medicine was studied in people living with early Alzheimer’s disease, including people with mild cognitive impairment due to Alzheimer’s disease.
The medicine was approved in the United States because it removes beta-amyloid plaques. But it hasn’t been widely used. Studies about its effectiveness at slowing cognitive decline are mixed. Insurance coverage also is limited.
Another Alzheimer’s medicine, lecanemab (Leqembi), has shown promise for people with mild Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s disease. The FDA approved the medicine in 2023. The medicine is given through an IV in the arm.
A phase 3 clinical trial found that lecanemab slowed cognitive decline in people with early Alzheimer’s disease by 27%. It works by removing beta-amyloid plaques in the brain. This study was the largest so far to look at whether clearing clumps of beta-amyloid plaques from the brain can slow the disease.
Another ongoing study is looking at how effective lecanemab may be for people at risk of Alzheimer’s disease. This includes people who have a first-degree relative, such as a parent or sibling, with the disease.
Donanemab, another monoclonal antibody, also has shown promise. The medicine has moved into a phase 3 study. Results are expected in 2023.
However, the monoclonal antibody solanezumab did not show benefits for individuals with preclinical, mild or moderate Alzheimer’s disease. Solanezumab did not lower beta-amyloid in the brain, which may be why it wasn’t effective.
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Preventing destruction. A medicine initially developed as a possible cancer treatment — saracatinib — is now being tested in Alzheimer’s disease.
In mice, saracatinib turned off a protein that allowed synapses to start working again. Synapses are the tiny spaces between brain cells through which the cells communicate. The animals in the study experienced a reversal of some memory loss. Human trials for saracatinib as a possible Alzheimer’s treatment are now underway.
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Production blockers. These therapies may reduce the amount of beta-amyloid formed in the brain. Research has shown that beta-amyloid is produced from a “parent protein” in two steps performed by different enzymes.
Several experimental medicines aim to block the activity of these enzymes. They’re known as beta- and gamma-secretase inhibitors. Recent studies showed that the beta-secretase inhibitors did not slow cognitive decline. They also were associated with significant side effects in those with mild or moderate Alzheimer’s. This has decreased enthusiasm for the medicines.
Keeping tau from tangling
A vital brain cell transport system collapses when a protein called tau twists into tiny fibers. These fibers are called tangles. They are another common change in the brains of people with Alzheimer’s. Researchers are looking at a way to prevent tau from forming tangles.
Tau aggregation inhibitors and tau vaccines are currently being studied in clinical trials.
Reducing inflammation
Alzheimer’s causes chronic, low-level brain cell inflammation. Researchers are studying ways to treat the processes that lead to inflammation in Alzheimer’s disease. The medicine sargramostim (Leukine) is currently in research. The medicine may stimulate the immune system to protect the brain from harmful proteins.
Researching insulin resistance
Studies are looking into how insulin may affect the brain and brain cell function. Researchers are studying how insulin changes in the brain may be related to Alzheimer’s. However, a trial testing of an insulin nasal spray determined that the medicine wasn’t effective in slowing the progression of Alzheimer’s.
Studying the heart-head connection
Growing evidence suggests that brain health is closely linked to heart and blood vessel health. The risk of developing dementia appears to increase as a result of many conditions that damage the heart or arteries. These include high blood pressure, heart disease, stroke, diabetes and high cholesterol.
A number of studies are exploring how best to build on this connection. Strategies being researched include:
- Current medicines for heart disease risk factors. Researchers are looking into whether blood pressure medicines may benefit people with Alzheimer’s. They’re also studying whether the medicines may reduce the risk of dementia.
- Medicines aimed at new targets. Other studies are looking more closely at how the connection between heart disease and Alzheimer’s works at the molecular level. The goal is to find new potential medicines for Alzheimer’s.
- Lifestyle choices. Research suggests that lifestyle choices with known heart benefits may help prevent Alzheimer’s disease or delay its onset. Those lifestyle choices include exercising on most days and eating a heart-healthy diet.
Hormones
Studies during the 1990s suggested that taking hormone replacement therapy during perimenopause and menopause lowered the risk of Alzheimer’s disease. But further research has been mixed. Some studies found no cognitive benefit of taking hormone replacement therapy. More research and a better understanding of the relationship between estrogen and cognitive function are needed.
Speeding treatment development
Developing new medicines is a slow process. The pace can be frustrating for people with Alzheimer’s and their families who are waiting for new treatment options.
To help speed discovery, the Critical Path for Alzheimer’s Disease (CPAD) consortium created a first-of-its-kind partnership to share data from Alzheimer’s clinical trials. CPAD‘s partners include pharmaceutical companies, nonprofit foundations and government advisers. CPAD was formerly called the Coalition Against Major Diseases.
CPAD also has collaborated with the Clinical Data Interchange Standards Consortium to create data standards. Researchers think that data standards and sharing data from thousands of study participants will speed development of more-effective therapies.
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May 20, 2023
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