For many years, researchers have believed that the brain is isolated from immune activity. But Prof. Michal Schwartz of Weizmann’s Brain Sciences Department has now overturned the long-held dogma and developed an innovative strategy for treating Alzheimer’s disease.
Schwartz revealed the critical role of age-related immune dysfunction in driving the progression of brain aging. In particular, she proposed that, regardless of a neurodegenerative disease’s primary cause, age-related decline of the immune system fuels brain inflammation, a major driver of disease progression. This finding suggested that removing amyloid plaques, long considered a hallmark of Alzheimer’s, is not enough to halt the disease. Her discoveries opened a new path toward developing treatments for neurodegenerative diseases by targeting the immune system.
In fact, a Phase 1b clinical trial of an Alzheimer’s disease immunotherapy based on Schwartz’s work has recently been completed, with the results published in Nature Medicine.
Instead of directly targeting Alzheimer’s amyloid plaque deposits, Schwartz’s team has focused on understanding how immune system dysfunction drives disease progression. This novel approach also reflects the growing recognition that Alzheimer’s disease is a systemic disorder, rather than solely a disease of the brain.
Following a series of successful studies in laboratory animals, the multicenter, international Phase 1 clinical trial enrolled 40 patients with early-stage Alzheimer's disease at 11 medical centers: five in the United Kingdom, five in Israel, and one in the Netherlands. The research was headed by Schwartz, while the clinical trial was led by Dr. Tommaso Croese, formerly a PhD student in Schwartz’s lab.
The trial’s results showed that the treatment was safe and well tolerated at all tested doses, and that its biological activity matched its engineered design. The treatment, aimed at reversing immune aging, also reduced biomarkers of neuronal damage, as well as biomarkers associated with loss of synaptic function. These findings support further clinical development of this innovative therapeutic strategy.
“Aging is the greatest risk factor for Alzheimer's disease,” Schwartz says. “Our research over the years has shown that one of the key contributors to disease progression is the aging of the immune system. Age-related decline in immune function fuels chronic inflammation in the brain, a major driver of the progression of Alzheimer’s disease and other neurodegenerative disorders.”
Schwartz concludes: “The goal of our biological therapy is to restore the immune system’s youthful capacity to protect the brain, thereby helping to arrest the disease or even reverse its course. We believe this approach could usher in a new era in the treatment of dementia and other neurodegenerative diseases, whose prevalence continues to rise as populations age and life expectancy increases.”
