GIFT15 is an experimental treatment for multiple sclerosis (MS).  It was developed and put through early laboratory tests by researchers at the Jewish General Hospital Lady Davis Institute for Medical Research and McGill University in Montreal.

How GIFT15 works

The symptoms of MS are caused by the immune system mistakenly damaging the myelin sheath, a protective layer that surrounds nerve fibers, resulting in the messages sent by nerves being disrupted and potentially leading to permanent nerve damage. The damage is caused by immune cells, or lymphocytes, such as B-cells. These lymphocytes can secrete proteins, called cytokines, that can trigger an immune response.

GIFT15 is a chimeric protein, a protein made in the laboratory by artificially fusing two cytokines together. Such a molecule is called a “fusokine,” or fusion cytokine protein. The two cytokines used to create GIFT15 are granulocyte macrophage-colony stimulating factor (GSM-CSF) and interleukin-15 (IL-15), which — when acting individually — trigger inflammation in tissues. But when fused together, GSM-CSF and IL-15 act to suppress the immune reaction. This is because the changed shape of the fusokine results in it interacting differently with immune receptors found on the surface of surrounding cells.

Exposing B-cells to GIFT15 can transform them into “regulatory B-cells,” which can inhibit the antigen-driven activation of certain T-cells; specifically, T-cells that target and attack cells with a specific antigen, which in MS can be against myelin.

GIFT15 in preclinical studies

GIFT15 completely reversed brain inflammation in mouse models of multiple sclerosis, but its potential as a treatment in humans is yet to be examined. It is thought likely to work only in the disease’s early stages.

The progression of experimental brain inflammation in mice is similar to MS in humans. In a preclinical study of GIFT15, researchers purified normal B-cells from the mice and then incubated them with GIFT15. When they injected the B-cells back into the sick mice, the symptoms of brain inflammation disappeared — T-cells were blocked, inflammation in the spinal cord stopped, and the mice recovered within four weeks of treatment. The results of this trial were published in the scientific journal Nature Medicine in 2009.

Researchers believe that the therapy can work as a personalized medicine for MS, as the B-cells used in the treatment will be ones harvested from the patient (in a process similar to donating blood). The B-cells will be treated in a Petri dish with GIFT15 and returned to the patient through an injection. Clinical studies are needed to test safety and efficacy of GIFT15  in humans, and the researchers are looking for a partnership or financial aid to undertake such studies.

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