Researchers are exploring CAR T-cell therapy to slow the advancement of amyotrophic lateral sclerosis (ALS) by targeting overactive immune cells in the brain. The approach aims to reduce neuron damage without curing the disease. Early studies suggest potential benefits for other neurodegenerative conditions as well.
Genetically engineered immune cells, known as CAR-T cells, could help slow the progression of amyotrophic lateral sclerosis (ALS), a neurodegenerative condition that leads to the loss of motor neurons controlling voluntary muscles. ALS, also called Lou Gehrig’s disease, has a life expectancy of two to five years after diagnosis, with fewer than 10 percent of patients surviving more than a decade. While treatments exist for the 5 to 10 percent of cases caused by genetic mutations, sporadic forms—which make up the majority—lack effective therapies.
Evidence points to brain inflammation as a key factor in motor neuron death. Specifically, immune cells called microglia can become overactive, removing too many synapses and contributing to neuron loss. Davide Trotti at the Jefferson Weinberg ALS Center in Pennsylvania explains that these "damage-amplifying microglia" display high levels of a protein called uPAR on their surface, acting as a tag for targeting.
Trotti's team has developed CAR-T cells engineered to recognize uPAR and eliminate these rogue microglia. In lab studies with cultured cells, the therapy killed the problematic cells without harming neurons. "It’s not a way to cure the disease," Trotti says. "The goal is slowing down the disease."
Current experiments involve mice with an ALS-causing mutation, with results anticipated in about a year. If promising, regulators may fast-track human trials given the disease's severity. Ammar Al-Chalabi at King’s College London notes, "The evidence for immune dysfunction in ALS is mounting. This seems a very promising and interesting approach to me."
The method might extend to other conditions involving similar microglia, such as certain dementias. However, CAR-T cells carry risks of serious side effects and high costs due to personalized manufacturing, though efforts are underway to improve safety and affordability.
