An experimental gene therapy with a hairy twist

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.

3 thoughts on “An experimental gene therapy with a hairy twist

  1. Melanin is a complex polymer that originates from the amino acid tyrosine. Melanin is present in human and animal skin to varying degrees, and is responsible for our unique eye, hair and skin. Melanin provides pigmentation to our skin, eye and hair. Melanin is produced in melanocytes. These cells are located in different areas of our body including hair, pupils, irises, substantia nigra, locus coeruleus, medulla zone reticularis and stria vascularis of cochlear duct. There are five basic types of melanin : eumelanin, pheomelanin, neuromelanin, allomelanin and pyomelanin. The most common types is eumelanin which can be divided into brown eumelanin and black eumelanin. Both of the black and brown hair come from different mixes of black and brown eumelanin. However, blonde hair happens when there’s a small amount of brown eumelanin and no black melanin. On the other hand, pheomelanin is responsible for red yellow tint hair color. The same amount of pheumelanin and eumelanin produces pinkish hair. Interestingly, strawberry blonde hair happens when brown eumelanin mixes with pheumelanin. In contrast, neuromelanin controls the colors of neurons. It isn’t involved with the coloring of things we see.

    Everyone has the same number of melanocytes, but some people make more melanin to get darker hair than others produced just a little bit of melanin to get light. As a whole, genes play key role to determine the amount of melanin made in our body. The introducing of new gene into blood stem cells with gene therapy ,may trigger white blood cells to increase cytokines or endogenous proteins production which is important to regulate gene expression and enzyme affinity. An increase of cytokine production may influence different types and levels of melanin produced by melanocytes in hair. Of course, melanocytes of hair produce high level of eumelanin mostly develop dark color of hair. Hence, the color of hair before and after gene therapy cannot be the same. In addition, cytokines have great impact to change the affinity of tyrosinase. Tyrosinase has critical roles to catalyze biosynthetic production of eumelanins and pheomelanins. Thus, different affinities of enzyme tyrosinase pose greater impact on both types of melanin production. Further investigation may provide evidence to support clinical investigation.

  2. Pingback: Weekly reads: NIH grants, side effect of darker hair, FDA warning, CRISPR – Rambam Wellness

  3. Wow! I’m amazed at the strides taken in the area of gene therapy and what it can do to restore hope to those who would otherwise have limited time to live. It’s even saddening to know that many life-threatening disorders affect children and teenagers. I believe the government should be at the forefront of sponsoring such studies and who knows, gene therapy may just be the answer to many disorders!

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