Mutant Heat Shock Protein Vaccine Prevents Vitiligo in Mouse Model

An experimental vaccine based on a genetically modified form of inducible heat shock protein 70 (HSP70i) prevented onset and partially cured vitiligo in a mouse model of the disease.

Vitiligo is skin disorder manifested by smooth, white spots on various parts of the body. Though melanocytes, the pigment-making cells of the skin, are structurally intact, they have lost the ability to synthesize the pigment. The reason for the condition is unclear although research suggests that it may arise from autoimmune, genetic, oxidative stress, neural, or viral causes. Individuals with vitiligo (about 1% of the adult population) are usually in good general health, but vitiligo presents a cosmetic problem that can be serious in dark-skinned individuals. Normal skin color rarely returns, and there is no known cure.

Investigators at Loyola University (Chicago, IL, USA) had shown previously that HSP70i played a vital role in the autoimmune response that causes vitiligo. In the current work they genetically modified one of HSP70i's 641 amino acids to create a mutant HSP70i molecule.

The investigators reported in the February 27, 2013, issue of the journal Science Translational Medicine that a vaccine based on the DNA encoding for mutant HSP70i applied months before spontaneous depigmentation prevented vitiligo in mice expressing a transgenic, melanocyte-reactive T-cell receptor. Furthermore, use of mutant HSP70i therapeutically in a different, rapidly depigmenting model after loss of differentiated melanocytes resulted in 76% recovery of pigmentation. Treatment also prevented relevant T-cells from populating mouse skin.

In addition to the dramatic results seen in the mouse model, “The mice look normal,” said senior author Dr. I. Caroline Le Poole, professor of pathology, microbiology, and immunology at Loyola University. Some of the beneficial effects of mutant HSP70i were seen in cultures grown from human vitiligo skin specimens.

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