Jordan Janz knows how lucky he is. It’s been almost six years since Jordan volunteered to be patient number one in a clinical trial at the University of California, San Diego (UCSD) to test a new treatment for cystinosis. People with this rare genetic disease accumulate the amino acid cystine in their organs. The toxic build-up causes severe symptoms, including respiratory problems, diabetes, blindness, and organ damage. Children with cystinosis often require kidney transplants, and in some cases, the condition can be fatal.
Now healthy and working, Janz joined UCSD’s Stephanie Cherqui, PhD, the scientists behind the development of his treatment, and Lisa McGinley, PhD, science officer on CIRM’s preclinical development team, in a recent webinar focused on transforming and developing new treatments for rare diseases. Janz took a beat before trying to describe his life before he underwent treatment.
“It’s kind of funny, but as I get older, I kind of forget … I don’t know, I just like, block it out,” Janz said during a webinar in late April focused on transforming the impact of rare disease research.
A clinical trial with a broader impact
We’ve written about Janz before, as well as Kurt Gillenberg, who also participated in this clinical trial. Both are still in remission, offering hope not just to others with this rare condition but also to those with other unrelated rare diseases. A rare disease, by definition, affects 200,000 or fewer people, but because there are so many of these conditions — more than 10,000 — about one in 10 people living in the US has a rare disease.
Cherqui, a professor in the Department of Pediatrics at UCSD, believes the stem–cell–based genetic therapy she developed to treat Janz, Gillenberg, and others with cystinosis could be used to develop treatments for other unrelated conditions.
To get to the stage of creating a therapy, you first need to understand the underlying biology.
More on cystinosis
In the case of cystinosis, researchers knew that a mutation in the CTNS gene prevented the body from removing the molecule cysteine from inside cells. The CTNS gene provides instructions for the cells to create a protein called cystinosin, a transporter protein within a membrane of lysosomes that acts as the cell’s “recycling bin,” breaking down material and transporting cysteine out of a cell.
The mutation interrupts that process, resulting in a toxic buildup of cysteine in every organ in the body, damaging them and leading to organ failure. Often, for children with cystinosis, the kidneys are the first organ to fail.
Cherqui and her team spent years perfecting a method of using stem cell genetic therapy to correct the mutation. Then they had the opportunity to test the experimental stem cell therapy in a clinical trial. Janz was the first patient to enroll.
The treatment changed Janz’s life, but it took years of effort and cost millions of dollars to develop. The treatment is still undergoing the final stages of clinical trials.
The California Institute for Regenerative Medicine (CIRM), which has been supporting Cherqui’s work on cystinosis for almost two decades through awards totaling about $30 million, is hoping to help many more others with rare diseases through a recently launched program called RAPID, or Rare Disease Acceleration Through Platform Innovation and Delivery. The $100 million program aims to accelerate therapies for rare diseases by developing treatments for several different conditions at one time.
From one therapy to many
The recent webinar, which included Janz, Cherqui, and CIRM’s McGinley, highlighted not only the development of the treatment for cystinosis but also how to leverage breakthroughs in rare disease treatments to create a model for developing treatments for related conditions.
“That’s what I want to do,” said Cherqui. “It’s very important to understand that everything we learn about a rare disease, every improvement in the technology, or every mechanism of action on a new therapy can be applied to so many other disorders.”
While Cherqui’s work has focused on developing therapies for individual diseases, each with a full development cycle and clinical trials, CIRM’s new program focuses on speeding that process more broadly for a number of different diseases.
Accelerating discovery
McGinley detailed how breakthroughs in a treatment for a rare disease like cystinosis — or another rare life-threatening disorder known as CPS1 deficiency, for which scientists recently found a potential new treatment, illustrated by the story of Baby KJ —could serve as a model to create a platform that would accelerate treatments for many other genetic diseases.
Why this is so important is that the drug development process is painstakingly slow and expensive. It often takes a decade or more to develop a drug. If you could reduce the time it takes and “de-risk” the process, you could accelerate the development of new treatments.
“Normally, each therapy for each disease must go through its own full development and testing process … and it can take a lot of time,” McGinley said. “So even for genetic therapies where development can be somewhat accelerated, it can still take many, many years, like five to 10 or more, to get from early development to FDA approval.”
Using a single-platform approach — whether through genetic editing, viral gene delivery, or RNA-based technology — developers could simultaneously generate multiple related therapies for multiple conditions.
What RAPID could accelerate
Just looking at the timeline and the work involved in Janz’s treatment highlights why a faster approach is needed.
Diagnosed at eight months old, Janz, like others with the condition, required dozens of medications every day to manage the disease, all with their own host of side effects.
“I think I was taking, like, 56 pills a day,” said Janz. “It was, like, 20-some in the morning, 20-some at night, and I think I threw up almost every morning, just because of the sheer number of pills I was taking.”
While the medication mediates some of the symptoms and prolongs the life of people with cystinosis, it doesn’t correct the underlying genetic disorder. Looking for an alternative to help her son, Janz’s mom learned about a clinical trial in California and made a phone call.
The promise of scalable genetic therapies
The therapy developed by Cherqui and her team involved collecting blood-forming stem cells from Gillenberg’s bone marrow and modifying the CTNS gene within those cells to produce a healthy copy of the protein. They then had to reintroduce those modified stem cells into a patient’s bone marrow, where they multiply and produce blood cells that can deliver the cytosine protein throughout the body. This, in turn, will infuse cells throughout the body and reduce cystine accumulation.
The treatment has already changed both Janz’s and Gillenberg’s lives and may yet help others with cystinosis.
None of these breakthroughs would have been possible without people like Janz and Gillenberg volunteering for clinical trials and without sustained funding to support understanding a disease through them.
You can find out more about CIRM-funded clinical trials or CIRM grant opportunities by visiting our website.
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