‘Temprian’ is an old English word that means ‘to restrain within due limits, to moderate’. At Temprian Therapeutics, we are passionate about finding an efficient treatment for Vitiligo. The company focuses on getting the mutant HSP70i-based drug subject to clinical trials. We will do this by partnering with patients, clinicians, investors, and the pharmaceutical industry. Here is how we look at the challenge: What is Vitiligo? Vitiligo is typically induced by a variety of stress factors ranging from exposure to harmful chemicals, intense sunlight, scrapes and bruises or emotionally draining conditions. The stress results in an immune response, where the body’s own T cells erroneously attack pigment cells (also called ‘melanocytes’) in the skin. Melanocytes are in charge of producing melanin, the pigment that gives the skin its color. Vitiligo tends to be progressive and evolves in stress induced bursts. The rate of pigment loss varies widely between individuals and may in due time result in complete depigmentation.
Vitiligo is an autoimmune disease that causes depigmentation.
Why does vitiligo occur? When subject to stress, cells in the skin start producing the heat shock protein HSP70i. This protein acts as a messenger that is crucial for maintaining the viability of the cell during stressful conditions, by shielding cellular molecules. Some heat shock proteins are transported out of the cell, from where they get taken up by so called dendritic cells and transported to local lymph nodes. Here the dendritic cells signal that something is wrong in the skin. This triggers the activation and recruitment of a variety of T cells, reactive with proteins transported by HSP70i. Such target proteins include melanocyte proteins. That leads to vitiligo in patients with pre-existing T cells that carry receptors aimed at recognizing and killing pigment cells.
Stress causes the body to express a heat shock protein that can trigger an autoimmune response on the pigment cells of the skin.
Why do T cells attack the body’s own cells? Activation of melanocyte reactive T cells is based on the T cells responding to a very specific protein transported to dendritic cells by the heat shock protein. The heat shock protein sounds the alarm, and the protein it carries is digested into peptides to form a “key”, that fits into a “lock” on the T cell. The chaperone function of HSP70 is thought to be very important, as it is very well preserved throughout evolution, and can be found in stressed cells from organisms ranging from bacteria to plants and mammals.
Heat shock proteins can convey a message that pigment cells need to be eliminated.
How would the therapy work? The heat shock protein-based vitiligo treatment is based on introducing a slightly modified version of HSP70i into the skin, where the alarm region has been re-engineered. The resulting heat shock protein scientifically named HSP70iQ435A now has the opposite effect on dendritic cells as compared to its natural counter-part. The modified heat shock protein actually acts as an immuno-suppressant, stalling the release of T cells. The lack of killer T cells in the skin now allows new pigment cells to occupy the skin, reversing the progression of vitiligo. The non-pigmented lesions start filling in with pigmentation.
A mutation turns a heat shock protein into an immune suppressant.
How will the drug be induced? The modified protein will be introduced into the skin by a series of DNA injections. Laboratory research with vitiligo disease models show that mice and swine respond well to four weekly treatments, to initiate the path to recovery.