In October 2019, 20‑year‑old Jordan Janz became the first person to receive an experimental gene therapy for cystinosis.
A rare disorder
Cystinosis is a rare genetic disorder in which cystine builds up in organs such as the kidneys, eyes, muscles, liver, pancreas, and brain. This buildup leads to multi‑organ failure and usually causes premature death. On average, people with cystinosis live to about age 28.5. By that measure, Janz had little time left.
The treatment was difficult but brought real benefits. The CIRM‑funded gene therapy seemed to work, and Janz began to feel better.
Then something unexpected happened. The cystinosis treatment changed his hair color his almost white‑blonde hair turned darker. Hair color was never expected to change. Yet four of the five patients in the trial—all white—also saw their hair darken.
Although surprising, the change didn’t signal a problem. Instead, researchers determined it might be a visible sign that the therapy was working.
A surprise side effect
The sudden hair‑color shift surprised Stephanie Cherqui, PhD, a stem cell scientist at UC San Diego and the trial’s principal investigator. But her team found no evidence that anything was going wrong. They concluded that the change might reflect successful gene correction.
How could modifying Janz’s blood cells change his hair color? Scientists targeted blood stem cells because some eventually become white blood cells that travel throughout the body. In this therapy, scientists engineered the new white blood cells to express CTNS, the mutated gene responsible for cystinosis. When these white blood cells reached the eyes, skin, and gut, they released the missing protein. Nearby cells absorbed the protein and cleared cystine crystals that had accumulated for a long time.
In Janz, the corrected proteins must have reached his hair follicles. Once excess cystine was removed, normal melanin production resumed, and his hair darkened.
Hair color has now become a useful way for patients to teach scientists more about the CTNS gene. Researchers have added hair biopsies to the trial to track these changes more systematically.
The outcome, while surprising to researchers, didn’t seem like a sign of something going awry; instead, they determined it might be a very visible sign that the gene therapy was working.
Read the full article on The Atlantic.
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.
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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!