Boston researchers have begun testing an innovative approach to treating Alzheimer's disease using a nasal spray containing a monoclonal antibody that targets brain inflammation rather than the disease's characteristic amyloid plaques and tau tangles.
Joe Walsh became the first Alzheimer's patient to receive foralumab, a monoclonal antibody initially developed for multiple sclerosis (MS), under special permission from the Food and Drug Administration (FDA). The treatment, administered at Brigham and Women's Hospital in Boston, aims to reduce neuroinflammation by modifying immune cell behavior in the brain.
A New Approach to Alzheimer's Treatment
Dr. Howard Weiner, a professor at Harvard and neurologist at Mass General Brigham, explained the mechanism behind foralumab: "It induces regulatory cells that go to the brain and shut down inflammation." This approach differs significantly from most Alzheimer's treatments, which focus on clearing amyloid plaques and tau tangles from the brain.
"Once people have Alzheimer's, the inflammation is driving the disease more," Dr. Weiner noted. "So if you give the drug to treat inflammation, the disease won't progress as much and the patients will do better."
The treatment's development was partly motivated by personal experience—Dr. Weiner lost his mother to Alzheimer's disease.
From MS to Alzheimer's: Repurposing a Promising Therapy
Foralumab was originally tested on people with multiple sclerosis, a condition where the immune system attacks the protective covering around nerve fibers, causing inflammation. After observing positive results in MS patients, researchers hypothesized that the same anti-inflammatory mechanism might benefit Alzheimer's patients.
Before treating Walsh, researchers had to obtain special permission from the FDA. The preliminary results, published in the journal Clinical Nuclear Medicine, indicate that inflammation in Walsh's brain has begun to subside after treatment.
"I've never seen anything like this, and we've tried a lot of things," Dr. Weiner remarked. "So I think this is something special." The treatment appears particularly promising because it has shown no serious side effects.
The Patient's Journey
Walsh's Alzheimer's journey began in 2017 when his wife, Karen, noticed he was struggling to find words to complete thoughts or sentences. After consulting a primary care physician, Walsh was referred to a neurologist, and in 2019, a PET scan confirmed his Alzheimer's diagnosis.
Karen Walsh immediately sought to enroll her husband in clinical trials for cutting-edge treatments. "As much as I was in shock, the words were ringing in my head—you know, ask for the research," she recalled.
Their initial efforts were derailed by the COVID-19 pandemic in March 2020, which led to the suspension of hundreds of clinical trials. By the time research resumed, Walsh's condition had progressed to moderate Alzheimer's, disqualifying him from most studies.
A Fortuitous Connection
In 2024, Karen brought Joe to Dr. Seth Gale, a neurologist at Mass General Brigham, who promised to watch for novel treatment opportunities. When a colleague inquired about patients with moderate Alzheimer's disease, Dr. Gale immediately thought of the Walshes.
"Dr. Gale called me, and he said, I think I have some research that Joe could be involved in. Would you be interested?" Karen Walsh recounted.
Early Signs of Improvement
While the drug cannot restore lost brain cells, and comprehensive cognitive testing is still needed to fully assess its impact on memory and thinking, Karen Walsh has observed positive changes in her husband's social engagement after six months of treatment.
"A couple of guys come pick him up once a month and take him out for lunch," she explained. "They sent me a text after, saying, 'Wow, Joe is really smiling, really laughing and very involved.' So that's where I'm seeing more of the change."
Joe Walsh himself has expressed satisfaction with the treatment: "It's easy enough to take it, and so I do it, and it feels good."
Looking Forward to Clinical Trials
Building on these encouraging preliminary results, a formal clinical trial of foralumab for Alzheimer's disease is scheduled to begin later this year. The trial will provide more comprehensive data on the treatment's efficacy and safety profile across a larger patient population.
If successful, this nasal spray could represent a significant advancement in Alzheimer's treatment, particularly for patients with moderate to advanced disease who may not benefit from current therapies targeting amyloid and tau proteins.
