Foralumab Nasal Spray Reduces Inflammation in Alzheimer's Disease

Key takeaways

• Consider different treatment methods for improving Alzheimer’s symptoms, removing amyloid plaques, and reducing inflammation.
• Discuss Alzheimer’s research with your neurologist—they can help you understand what medications might be helpful at your stage of the condition.
• Learn about the latest research into Alzheimer’s treatments at the Mass General Brigham Neuroscience Institute like a potential nasal vaccine, Xenon gas, or changes to the microbiome.

Over 7 million Americans are living with Alzheimer’s disease (AD), the most common form of dementia. Alzheimer’s impacts memory, thinking, and behavior, and is more than simple forgetfulness or normal signs of aging.

Mass General Brigham is on the forefront of Alzheimer’s research, investigating causes, treatments, and an eventual cure. In this article, Howard L. Weiner, MD, explains a new treatment—a nasal spray called foralumab—that is changing the treatment landscape for people with Alzheimer’s.

Dr. Weiner is a Mass General Brigham Neuroscience Institute neurologist and scientist, currently researching new Alzheimer’s treatments. He serves as co-director of the Ann Romney Center for Neurologic Diseases, home to multidisciplinary biomedical research laboratories focused on finding cures more quickly.

What is Alzheimer’s disease?

Alzheimer’s disease is a progressive disease that causes memory loss and cognitive problems. AD develops and progresses through amyloid plaques (a protein that builds up between cells) and tangled nerves in the brain. As these abnormal structures damage surrounding brain tissue, people experience more symptoms of Alzheimer’s such as memory loss, problems speaking, and changes in behavior.

Treatments for Alzheimer’s disease

There is no cure for Alzheimer’s disease. There are several treatment options to help people with Alzheimer’s, including:

• Medications that treat symptoms and complications, such as medicine to reduce agitation
• Anti-amyloid medications that slow disease progression by removing amyloid plaques in the brain
• Anti-inflammatory medication that reduces inflammation in the brain, improving symptoms

Two medications have been FDA-approved to slow Alzheimer’s progression by removing amyloid plaques—donanemab and lecanemab. These medications are effective in the very early stages of Alzheimer’s disease and moderately slow disease progression.

“The anti-amyloid drugs currently approved for Alzheimer’s are just for mild disease,” notes Dr. Weiner. The nasal spray foralumab works differently. Dr. Weiner explains, “Inflammation is important in causing problems in Alzheimer’s. This treatment suppresses the inflammation.”

How does foralumab work?

Foralumab targets the inflammation in the brain caused by the plaques and tangles. It’s a monoclonal antibody, which is a protein made in a lab based on human antibodies. It’s taken as a nasal spray and targets the CD3 protein complex on T cells, a type of white blood cell important in the immune system.

Your nose is an extremely important part of your immune system. The nasal mucosa (the moist lining inside the nose) is home to important immune cells called regulatory T cells, or Tregs. Tregs help prevent the body from attacking its own cells.

In targeting the CD3 protein on T cells, foralumab causes the Tregs to travel to the brain and release anti-inflammatory chemicals. “Those anti-inflammatory cells go through the blood back to the areas of inflammation in the brain,” says Dr. Weiner.

The importance of nasal delivery

While many medications for Alzheimer’s and other conditions are delivered through an IV or an injection, foralumab is given as a nasal spray.

“The immune system in the nasal cavity is special,” Dr. Weiner says. “The medicine induces T cells to create anti-inflammatory chemicals without side effects. The same medicine given through IV or an injection under the skin kills T cells and suppresses the immune system.”

What are the results of Alzheimer’s treatment with foralumab?

Foralumab treatment for Alzheimer’s reduces inflammation in the brain, which leads to a reduction in symptoms. “The first patient treated with foralumab showed a dramatic decrease in the inflammation in the brain,” says Dr. Weiner.

The reduction in inflammation is seen on a PET (positron emission tomography) scan of the patient’s brain. Dr. Weiner notes, “Just as you can see inflammation from pneumonia on PET imaging of the lungs, and see the reduction after treatment, we see the reduction in inflammation in the brain after foralumab treatment in patients with Alzheimer’s.”

Dr. Weiner explains that once you have Alzheimer’s, the inflammation is doing a lot of damage to the brain. The hope is that reducing the inflammation will slow disease progression and improve symptoms for people living with Alzheimer’s.

“It could be a game changer. It could offer a whole new way to treat Alzheimer’s,” says Dr. Weiner.

Side effects of foralumab

One of the major benefits of foralumab has been the absence of side effects. In part, this is because foralumab doesn’t enter the bloodstream, so it doesn’t impact the liver, kidneys, or blood the way other medications might.

“This is groundbreaking,” Dr. Weiner says. “No one has drugs that affect the immune system like this that have no side effects. You’re harnessing the body’s own immune system to reduce inflammation and treat Alzheimer’s and other conditions.”

Foralumab research across Mass General Brigham

Inflammation is a major factor in many conditions, particularly those of the central nervous system (the brain, spinal cord, and nerves). Neuroinflammation can cause or worsen many CNS (central nervous system) conditions and their symptoms. In addition to treating patients with Alzheimer’s, researchers across Mass General Brigham are testing foralumab in patients with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and multisystem atrophy. It is also being tested in animal models of Parkinson’s disease, traumatic brain injury, stroke, intracerebral hemorrhage, epilepsy, long COVID, aging, and obesity in preparation for future human clinical trials

“We’ve also seen positive results in patients with MS. In a couple of patients with a form of Parkinson’s, we’ve seen changes in the brain. We’re starting a trial in ALS soon,” notes Dr. Weiner.

“We collaborate with people across Mass General Brigham. We’re able to access and work with people across the entire organization to improve care for all our patients,” he adds.

What’s next in Alzheimer’s research?

While foralumab treatment for Alzheimer’s is encouraging, it’s not the only treatment tactic Dr. Weiner and researchers at Mass General Brigham are working on.

Alzheimer’s nasal vaccine

Another nasal spray stimulates monocytes and macrophages—immune cells that destroy damaged cells and clean up dead cells—to clear amyloid plaques in the brain.

Dr. Weiner says, “The monocytes and macrophages are dysfunctional in Alzheimer’s. The nasal vaccine sends the monocytes and macrophages through the blood to the brain to clean up the amyloid.”

He continues, “Foralumab is used to treat Alzheimer’s, but the nasal vaccine could be given very, very early to prevent Alzheimer’s.”

Xenon gas treatment

Xenon is an inert gas previously used in medicine primarily as an anesthetic. When inhaled, Xenon can cross the blood-brain barrier, entering the fluid around the brain to treat the inflammation.

“We found that Xenon gas helped with Alzheimer’s in animals,” says Dr. Weiner. The study found that Xenon gas inhalation suppressed neuroinflammation, reduced brain atrophy, and increased protection of the structure and health of neurons in mouse models of Alzheimer’s disease.

“We’re testing it in healthy volunteers next before testing in Alzheimer’s patients,” says Dr. Weiner. The clinical trial with healthy volunteers will help determine safety and dosing before moving on to treating patients with Alzheimer’s.

The Xenon inhalation treatment could reduce the damage from Alzheimer’s and help clear amyloid plaques. Like foralumab, Xenon gas treatment could be effective in other CNS conditions.

Alzheimer’s and the microbiome

“We’re also studying the microbiome in relation to Alzheimer’s,” says Dr. Weiner.

Researchers have found connections between the microbiome and a variety of conditions, including irritable bowel syndrome (IBS), post-traumatic stress disorder (PTSD), allergies, and cancer.

“The microbiome—all the bacteria in the gut—is very important in human disease. We’re studying whether specially designed probiotics can impact Alzheimer’s.”

The research progress on treatments for Alzheimer’s gives hope to people living with Alzheimer’s disease, and their families, friends, and loved ones.

“There’s almost no one that doesn’t have a personal connection to Alzheimer’s, because it’s so prevalent,” says Dr. Weiner, who lost his mother to Alzheimer’s. “We’re able to collaborate with people across the entirety of Mass General Brigham to make progress on treating and preventing Alzheimer’s.”