According to the National Organization for Rare Disorders (NORD), a disease is consider rare if it affects fewer than 200,000 people. If you combine the over 7,000 known rare diseases, about 30 million people in the U.S. are affected by one of these conditions. A majority of these conditions have no cure or have very few treatment options, but a CIRM funded trial (approximately $12 million) for a rare pediatric disease has showed promising results in one patient using a gene therapy approach. The hope for the field as a whole is that this proof of concept might pave the way to use gene therapy to treat other diseases.
Cystinosis is a rare disease that primarily affects children and young adults, and leads to premature death, usually in early adulthood. Patients inherit defective copies of a gene that results in abnormal accumulation of cystine (hence the name cystinosis) in all cells of the body. This buildup of cystine can lead to multi-organ failure, with some of earliest and most pronounced effects on the kidneys, eyes, thyroid, muscle, and pancreas. Many patients suffer end-stage kidney failure and severe vision defects in childhood, and as they get older, they are at increased risk for heart disease, diabetes, bone defects, and neuromuscular problems. There is currently a drug treatment for cystinosis, but it only delays the progression of the disease, has severe side effects, and is expensive.
Dr. Stephane Cherqui at UC San Diego (UCSD), in partnership with AVROBIO, is conducting a clinical trial that uses a gene therapy approach to modify a patient’s own blood stem cells with a functional version of the defective gene. The corrected stem cells are then reintroduced into the patient with the hope that they will give rise to blood cells that will reduce cystine buildup in the body.
22 year old Jordan Janz was born with cystinosis and was taking anywhere from 40 to 60 pills a day as part of his treatment. Unfortunately the medication affected his body odor, leaving him smelling like rotten eggs or stinky cheese. In 2019, Jordan was the first of three patients to participate in Dr. Cherqui’s trial and the results have been remarkable. Tests have shown that the cystine in his eyes, skin and muscle have greatly decreased. Instead of the 40-60 pills a day, he just takes vitamins and specific nutrients his body needs. What’s more is that he no longer has a problem with body odor caused by the pills he once had to take. Although it will take much more time know if Jordan was cured of the disease, he says that he feels “essentially cured”.
In an article from the Associated Press, Jordan is optimistic about his future.
“I have more of a life now. I’m going to school. I’m hoping to open up my own business one day.”
You can learn more about Jordan by watching the video below:
Although gene therapy approaches still need to be closely studied, they have enormous potential for treating patients. CIRM has funded other clinical trials that use gene therapy approaches for different genetic diseases including X-SCID, ADA-SCID, ART-SCID, X-CGD, and sickle cell disease.
The Stem Cellar 
Gene therapy is the treatment of any disorder or pathophysiologic state based upon transfer of a normal copy of a single defective gene would revert the disease pathogenesis or prevent the development of disease. However, technical factors related to gene therapy remain a major impediment to widespread application of this technology. The efficiency of gene therapy is depended on the feasible of technology to deliver the therapeutic gene to the appropriate target cell and expression of therapeutic gene must be selective at a defined level, in the target cell. Moreover, transfer and expression of the therapeutic gene must not be deleterious to the patient or present a health hazard to bystanders. Current gene therapy to treat Cystinosis by modifying a patient’s own blood stem cells with a functional version of the defective gene. Then the modifying cells are reintroduced into patients to give rise to blood cells. The approach of genetically modifying cells ex vivo and then reinfused to the patient had limitations, largely in the contexts of not all patients’ target cells can equally propagate and maintain in tissue culture for prolonged periods of time after gene transfer. The second criteria is gene transfer vectors is designed to exploit the efficient cellular entry characteristic to accomplish delivery of a therapeutic gene. Viral vectors with high efficiency of gene tranduction are widely used in gene therapy than nonviral vectors. The promoter of viral vectors play critical role to regulate the levels of gene expression. Viral promoter with the potential to upregulate gene expression may require small number of targeted cells to archive clinical response. Whereas, viral promoter with downregulate of gene expression may require high number of transfected cells for optimal clinical response. In addition, the ability of some virions elicit a prominent inflammatory response shouldn’t be taken lightly. The diverse immune response among the patients may substantially halt the efficiency of gene therapy. Lastly, the possibility of viral gene functions may affect gene expression patterns in the targeted cells. For instance, viral vectors associated with an integration step has high risk for viral DNA insertion into the genome of targeted cell which may cause neoplastic transformation cannot be entirely rule out. Therefore, a therapeutic window of nontoxic but efficacious dose of recombinant virions made gene therapy a realistic goal for medicine in variety of genetic diseases including X-SCID, ADA-SCID, ART-SCID, X-CGD and Sickle Cell Disease.