Summary of the Research on CAR-T Therapy and Cognitive Impairment (“Brain Fog”)
This research investigates a surprising side effect of CAR-T cell therapy: cognitive impairment, or “brain fog,” even in cancers not located in the brain. Here’s a breakdown of the key findings:
* CAR-T therapy can cause lasting cognitive problems: Mice with various cancers (including those spreading to or outside the brain) experienced cognitive decline after CAR-T treatment, measured thru novel object recognition and maze navigation tests. The exception was mice with bone cancer causing minimal inflammation.
* This is a novel finding: This study is the first to demonstrate that immunotherapy alone can induce lasting cognitive symptoms.
* The mechanism involves brain immune cells (microglia): The body’s immune response to the cancer and CAR-T cells activates microglia in the brain. Thes activated microglia release inflammatory molecules (cytokines and chemokines).
* Inflammation damages myelin: These inflammatory molecules harm oligodendrocytes, the cells responsible for producing myelin – the insulation around nerve fibers. Reduced myelin leads to slower nerve signal transmission and cognitive impairment.
* Human evidence supports the findings: Analysis of postmortem brain tissue from human patients undergoing CAR-T therapy for brain/spinal cord tumors showed similar dysregulation of microglia and oligodendrocytes.
* Potential treatments identified in mice:
* Transient microglia depletion: Temporarily removing microglia allowed them to return in a healthy state and restored cognitive function.
* Blocking chemokine signals: A medication blocking a specific chemokine receptor also rescued cognition.
* Unifying principle for brain fog: The research suggests a common underlying mechanism for various brain fog syndromes, including those caused by chemotherapy, radiation, COVID-19, and influenza.
* Future directions: Researchers are working to translate these findings into safe treatments for people experiencing cognitive impairment after CAR-T therapy.
In essence,the study reveals that the systemic immune response triggered by CAR-T therapy can inadvertently impact the brain,leading to cognitive problems through inflammation and myelin damage. However, it also offers promising avenues for potential treatment.
