In October 2019, 20-year-old Jordan Janz became the first person in the world to receive an experimental therapy for cystinosis. Cystinosis is a rare genetic disorder characterized by the accumulation of an amino acid called cystine in different tissues and organs of the body including the kidneys, eyes, muscles, liver, pancreas, and brain. This accumulation of cystine ultimately leads to multi-organ failure, eventually causing premature death in early adulthood. On average, cystinosis patients live to 28.5 years old. By that calculation, Janz didn’t have a lot of time.
The treatment was grueling but worth it. The experimental gene therapy –funded by the California Institute for Regenerative Medicine– seemed to work and Janz began to feel better. There was, however, an unexpected change. Janz’s almost white, blonde hair had settled into a darker tone. Of all the things the gene therapy was expected to alter –such as the severity of his cystinosis symptoms– hair color was not one of them. Eventually, the same phenomenon played out in other people: So far in the gene-therapy trial, four of the five patients –all of whom are white– have gotten darker hair.
The outcome, while surprising to researchers, didn’t seem to be a sign of something going awry, instead they determined that it might be a very visible sign of the gene therapy working.
The sudden hair-color changes were surprising to Stephanie Cherqui, a stem-cell scientist at UC San Diego and the principal investigator of the gene-therapy trial. However, it didn’t seem to be a sign of something going awry, instead Cherqui and her colleagues determined that it might be a very visible sign of the gene therapy working.
But exactly how did genetically modifying Janz’s (and other participants’) blood cells change his hair color? In this instance, scientists chose to genetically tweak blood stem cells because they have a special ability: Some eventually become white blood cells, which then travel to all different parts of the body.
Janz’s new white blood cells were genetically modified to express the gene that is mutated in cystinosis, called CTNS. Once they traveled to his eyes, skin, and gut, the white blood cells began pumping out the missing protein encoded by the gene. Cells in the area began taking up the protein and clearing away long accumulated cystine crystals. In Janz, the anti-cystine proteins from his modified blood cells must have reached the hair follicles in his skin. There, they cleared out the excess cystine that was blocking normal melanin production, and his hair got darker.
Hair color is one way in which patients in the clinical trial are teaching scientists about the full scope of the CTNS gene. The investigators have since added hair biopsies to the trial in order to track the color changes in a more systematic fashion.
Read the full article on The Atlantic.