Alzheimer’s Treatments: What’s Coming?

Alzheimer’s disease is one of the most dreaded and devastating illnesses worldwide. Not only does the neurodegenerative disorder affect individuals diagnosed with the disease, but it also impacts their family members who care for them, sometimes with assistance from a caregiver.

More than seven million Americans 65 and older are living with Alzheimer’s disease, according to the Alzheimer’s Association. Alzheimer’s, the most common form of dementia, causes a gradual decline in cognitive functions such as memory, thinking, and reasoning skills. The disease ultimately impacts an individual’s daily life and leads to death.

Currently, there is no cure for the Alzheimer’s disease. However, researchers are cautiously optimistic about developing treatments that can stop or delay the progression of the disease.

New Medications Approved To Treat Alzheimer’s

Some of the new Alzheimer’s treatments target amyloid-beta, the protein that forms clumps in the brain known as plaques. Besides beta-amyloid, researchers are also focusing on the tau protein that can build up in the brain and form “tangles” that damage brain cells. Both amyloid beta plaques and tau tangles are key features of Alzheimer’s disease.

The U.S. Food and Drug Administration (FDA) has approved medications known as monoclonal antibodies that prevent the amyloid-beta protein from clumping into plaques and remove existing plaques. The drugs work by helping the body clear them from the brain. The medications also imitate the antibodies that the body naturally produces as part of the immune system’s response to foreign invaders or vaccines.

Two of the medications that received FDA approval are lecanemab (Leqembi) and donanemab (Kisunla), both of which were found in clinical trials to slow down decline in thinking and functioning in people with early Alzheimer’s disease. The medicines prevent amyloid plaques in the brain from clumping. The FDA approved the medications for people with mild Alzheimer’s disease and mild cognitive impairment due to Alzheimer’s.

Lecanemab is administered as an IV infusion every two weeks, while donanemab is given as an IV every four weeks. Lecanemab, however, has infusion-related side effects, such as fever, flu-like symptoms, nausea, vomiting, dizziness, altered heart rate, and shortness of breath.

Donanemab is given as an IV infusion every four weeks. Side effects of the medicine may include flu-like symptoms, nausea, vomiting, headache, and changes in blood pressure.

Both medications, however, carry rare but serious risks. For instance, patients taking lecanemab or donanemab may have:

1. Swelling in the brain. In rare cases, brain swelling can become severe enough to cause seizures and other symptoms.

2. Small bleeds in the brain. In rare instances, bleeding in the brain can cause death. Blood-thinning medications can increase the risk of brain bleeds, which is why a discussion with a healthcare professional is necessary before taking lecanemab or donanemab.

Because of these complications, the FDA recommends getting a brain MRI periodically during treatments to check for symptoms of swelling or bleeding.

People who have a particular type of the APOE e4 gene, which increases the risk for Alzheimer’s disease, seem to be more likely to develop these severe problems. The FDA recommends getting tested for this gene before starting treatment.

While lecanemab and donanemab have helped people with early Alzheimer’s, research continues on the potential risks of these medications. In addition to the risks, scientists are also looking at how effective the medicines may be for people who are at risk of Alzheimer’s disease, including those who have a parent or sibling with the disease.

Cancer Drug Under Consideration for Treating Alzheimer’s

Saracatinib, a drug developed by AstraZeneca to treat cancer outside the brain, is now being investigated as a potential treatment for Alzheimer’s disease.

Scientists from AstraZeneca, a global pharmaceutical company, and Yale University School of Medicine gave the experimental drug to mice with symptoms mimicking Alzheimer’s disease, such as memory problems and age-related buildup of abnormal amyloid-beta clusters.

After four weeks, the scientists observed changes in the mice, including a complete reversal of spatial learning and memory loss, as well as the restoration of synapses, which enable neurons in the brain to communicate with each other. The scientists stated that restoration of the synapses provided a biological explanation for the memory improvement.

Due to the success of reversing brain issues in the mice, scientists are now testing saracatinib on humans.

Preventing Tau From Forming Tangles

Scientists have discovered that an abnormal buildup of the tau protein can lead to “tangles.” The tangles form when tau twists into tiny fibers that can cause cell damage and inflammation in the brain. Tau and amyloid are the two main proteins scientists believe interfere with communication between brain cells and contribute to Alzheimer’s disease and other dementias.

Scientists are currently conducting clinical trials on tau aggregation inhibitors and tau vaccines that can prevent the tau protein from forming tangles.

Reducing Brain-Cell Inflammation

Scientists are exploring the use of sargramostim (Leukine), a protein that stimulates the production and activation of different immune cells, to treat Alzheimer’s disease. Alzheimer’s causes persistent low-grade brain cell inflammation, and scientists are researching ways to treat the underlying causes of inflammation. Researchers believe sargramostim may stimulate the immune system to protect the brain against harmful proteins.

Continuing To Research The Heart-Head Connection

More studies are suggesting that the risk of developing dementia seems to increase due to the many conditions that can damage the heart or arteries, such as high blood pressure, heart disease, stroke, diabetes, and high cholesterol. As a result, researchers are exploring whether there is a connection between the heart and the head. Some of the studies include:

• A closer examination of how the link between heart disease and Alzheimer’s operates at the molecular level. This type of research aims to find new potential medications for Alzheimer’s.

• Whether lifestyle choices, such as exercising most days and eating a heart-healthy diet with known heart benefits, may help prevent Alzheimer’s disease or delay its onset.

Some Efforts Have Not Been Successful

While there have been some successes in finding treatments for Alzheimer’s, there have also been some less successful research efforts. For example, researchers are studying how changes in insulin within the brain may be connected to Alzheimer’s. However, a clinical trial of an insulin nasal spray found that the medication was not effective in slowing the disease’s progression.

Also, people with preclinical, mild, or moderate Alzheimer’s disease did not benefit from solanezumab, a monoclonal antibody. Studies found that solanezumab did not reduce amyloid-beta in the brain, which may explain why it wasn’t effective.

Regardless of setbacks, scientists are constantly increasing their understanding of how Alzheimer’s impacts the brain while finding ways to help older adults fight the disease.

Source Links:

https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-treatments/art-20047780
https://ncats.nih.gov/pubs/features/ntu-alzheimers-treatment