Imatinib, a cancer treatment, stopped an injury response mechanism of the central nervous system (CNS) from activating, damage to which is a hallmark of multiple sclerosis (MS), an early study reported.
Treatment with imatinib lessened immune cell infiltration and eased disease progression in mouse models of MS. Study researchers suggested that treatments with a similar mechanism of action might be of benefit in neurological diseases marked by BBB disruption.
The study “Blocking PDGF-CC signaling ameliorates multiple sclerosis-like neuroinflammation by inhibiting disruption of the blood–brain barrier” was published in the journal Nature Scientific Reports.
Disruption of the BBB and subsequent entry of immune cells to the CNS (brain and spinal cord) is a hallmark of various disorders, including MS. This barrier is a natural, highly selective membrane that shields the CNS from insults that can be carried in the blood.
Researchers at the Karolinska Institute, in Sweden, evaluated whether the loss of brain-blood barrier’s integrity would change during the different stages of MS — specifically, its preclinical (before symptoms evident), progression, and remission stages.
They first performed a genetic analysis of endothelial cells — which line the interior of blood vessels — isolated from vessels in the spinal cords of an established animal model of MS, the experimental autoimmune encephalomyelitis (EAE) mouse model. Cells from EAE mice were recovered at each of these disease phases, as were cells from control mice without EAE.
Analysis revealed gene activity changed significantly at all three phases in the EAE mice compared with control mice. Changes were detected in 59 genes during the preclinical, 1,571 during the progression, and 781 during the remission stage. Of note, 26 of these genes were common for all three disease stages.
In a previous study in a rat EAE model, the researchers showed that treatment with imatinib, approved to treat certain types of leukemia (a cancer that begins in white blood cells) and other cancers, preserved BBB integrity and ameliorated clinical symptoms of the disease. Imatinib inhibits a common injury response mechanism of the CNS that is mediated by the activation of the platelet-derived growth factor receptor alpha (PDGFR-alpha) signaling.
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