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Gene immunotherapy protects against MS in mice
October 10, 2017
A University of Florida study suggests a gene immunotherapy approach may prevent and reverse symptoms of multiple sclerosis in mice. The researchers used a viral technique to deliver genetic information to the liver, producing immune tolerance in mice by preventing T cells from attacking the myelin sheath.
MS is thought to result from activation of T cells that attack myelin sheath proteins. Normally, regulatory T cells curb the self-destructive activity of effector T cells, and maintain immune tolerance. The transfer of regulatory T cells to mice with a MS-like disease can temporarily prevent or reduce neurological symptoms. While injection of regulatory T cells appears to be safe and effective, these approaches are not sufficiently potent or long-lasting.
To overcome this hurdle, the researchers developed a strategy using the liver’s ability to create immune tolerance. They used an adeno-associated virus (AAV) vector – similar to those currently being evaluated in clinical trials – to deliver a myelin sheath protein to the liver in a mouse model of MS. A single injection effectively produced immune tolerance, stimulating regulatory T cells that protected the myelin sheath by suppressing self-destructive effector T cells.
This approach protected mice from developing signs of MS during a seven-month period, showing stable and robust immune tolerance. Moreover, the treatment reversed symptoms in mice that had already developed mild to moderate neurological deficits, and even restored mobility in mice that had developed more severe symptoms, such as hind-leg paralysis.
When AAV immunotherapy was combined with a short dose of the immunosuppressive drug rapamycin, the result was complete remission in nearly all mice at late stages of the disease, restoring mobility after severe paralysis and protecting mice from symptoms until the end of the experiment approximately 100 days later. However, results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment.
The study was published in the journal
Molecular Therapy
.
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