An Emerging Gene Therapy in Turkey Could Bring Hope to Patients

Gazi University making waves as they pursue new research and clinical trials

(Main photo credit: Gazi Üniversitesi)

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a progressive, painful disease that results in high blood phosphate and is characterized by non-cancerous calcium phosphate deposits throughout the body. In mild cases it can cause issues in the eyes and feet, but worse cases can mean deposits in the joints that impair movement, or even deposits in the brain. 

“I am working in one of the busiest centers (in Turkey), taking care of patients with both metabolic disorders and syndromic disorders,” said Dr. Fatih Süheyl Ezgü, Professor of Pediatrics and Head of the Department of Pediatric Genetics Disorders at Gazi University. “So, as you know, these two groups constitute the majority of the genetic diseases in childhood.”

HFTC is a rare, recessive disease, but due to the prevalence of consanguineous marriages in Turkey (marriages between people who share a blood relation), there are more patients than average for recessive diseases. Understanding the danger, researchers from Gazi University decided to take action and start the first ever gene therapy trials in Turkey. HFTC was chosen as the target partially for its promising gene target, but also because it offers the opportunity to gain practice in several crucial areas of treatment.

“If you consider the whole body, it is most difficult to treat diseases which involve central nervous system,” Dr. Ezgü said, due to the difficulty in administering drugs to the brain. “So, considering that this disorder is a disease that involves the brain, we thought it would be a good candidate to develop a gene therapy.”

Another area of difficulty is that the enzyme they will be trying to replace through gene therapy is secreted from the bone – another area that is difficult for researchers to access. So given a promising target and at least two critical areas of the body that are difficult to deal with, HFTC was the ideal candidate. It offers learning opportunities while still having an achievable target.

“We had many meetings, drank a lot of coffee, and then decided that OK, this will be our target disorder,” Dr. Ezgü said. “The experience we would get would be a huge, especially in Turkey, considering that we do not have such an effort in other diseases.”

The next step was to determine where to get funding and help. The Turkish Council of Higher Education, recognizing the potential not only for this disease but for the gene therapy pathways it could open, designated their department as a department of priority, meaning they recognized their potential for medical progress, and allocated some funding for the venture. 

They then reached out to established industry leaders, including Charles River, for help with the starting material. Charles River agreed to collaborate by providing plasmid DNA for Gazi’s AAV production. News of this and other collaborations spread through the scientific community in Turkey, stirring excitement for this completely new endeavor for the country. Customs will need to learn how to accept plasmids, new protocols will need to be put in place, and everywhere they look, researchers will be building new initiatives. “Now if we study a second disorder, all these steps that took a couple of months will be just one week,” Dr. Ezgü said.

With all of the excitement, Dr. Ezgü and the rest of the team are not losing focus on the main goal: helping patients.

“We do not want this to be commercialized,” Dr. Ezgü said. The plan is to give the finished product to the government for mass distribution, and to prove that a collaboration between local academic and international industry can work as a model for gene therapy development in Turkey.