FA: Immune System Drug Strengthens Mice

Treatment with an engineered version of the naturally produced interferon gamma protein enhanced the ability to move, and improved balance and coordination in mice with a disease resembling Friedreich's ataxia (FA), a team of researchers has reported. In addition, treatment with interferon gamma prevented degeneration of sensory neurons (nerve cells) in the mice.

Interferon gamma is naturally produced in the body's cells, where it plays multiple roles in the immune response, including regulation of the availability of iron.

Its beneficial effects in FA appeared to be the result of increased production (upregulation) of the frataxin protein. (A deficiency of frataxin is the molecular cause of FA, and results in an inability of the body to properly manage iron.)

The research team, based in Italy and the United Kingdom, says that its data provide grounds for interferon gamma to be evaluated as a possible treatment for FA.

Marketed under the brand name Actimmune, interferon gamma is approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic granulomatous disease and severe, malignant osteopetrosis. (Chronic granulomatous disease is characterized by defects in the immune system that result in the aggregation of cells and other biological materials into clumps called granulomas.  In osteopetrosis, bones become dense and prone to fractures.)

Interferon gamma raises frataxin levels

After initial data indicated that interferon gamma might increase production of frataxin, study investigators tested the protein with cancer cells from a variety of different cultured human cell lines. They found that after 24 hours of exposure to interferon gamma, cellular levels of frataxin increased in a dose-dependent manner (higher levels at higher doses) in all three types of cells.

A similar dose-dependent upregulation of frataxin occurred in cells taken from healthy volunteers and from people with FA.

Next, the investigators tested interferon gamma in a mouse model of FA.

Thirteen mice were treated with subcutaneous (under the skin) injections of interferon gamma at 40 micrograms per kilogram of body weight, three times a week, starting at 8 weeks old for a total of 14 weeks. An additional 13 mice were treated with an inactive substance, using the same schedule.

The investigators assessed the mice every two weeks and found that the mice treated with interferon gamma had significantly enhanced movement ability, moving farther and at a faster average speed than the mice that received the inactive substance. The interferon gamma-treated mice also did significantly better on a test that measures coordination, strength and balance.

The data suggest that interferon gamma causes increased levels of frataxin in FA-affected cells by increasing frataxin messenger RNA, or mRNA (the final code or "recipe" that a cell uses in the protein-building process), although the researchers note that additional mechanisms for increasing frataxin may be at work as well.

Further development possible

Further research is needed before interferon gamma can be developed as a possible treatment for FA. The regulatory approval process could be shortened, however, as the protein already has been approved by the FDA to treat other disorders.

Complete study results were published in the July 1, 2012, issue of Human Molecular Genetics. To read the full report, free of charge, see Interferon Gamma Upregulates Frataxin and Corrects the Functional Deficits in a Friedreich Ataxia Model.


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