Teen girl receives world-first gene replacement therapy in Shanghai for rare genetic disease

A 16-year-old girl has received gene replacement therapy at Shanghai Children's Medical Center to treat her pyruvate kinase deficiency, a rare genetic disorder that causes the red blood cells to break down faster than normal.

She is the first patient in the world to receive such treatment, creating a new era in clinical practice.

The patient started to develop serious anemia upon birth and has had to depend on blood transfusions since.

She was diagnosed with PKD in 2022 and the family applied to participate in the clinical research at Shanghai Children's Medical Center in 2023.

The research began in January, since when her doctors removed and preserved ovary tissue and follicles to ensure her future fertility, collected her hematopoietic stem cells, and performed in vitro genome editing.

She has been receiving transfusions of the edited stem cells for the past two months and has regained a proper haematogenous function. The patient has now been discharged after her recovery, the hospital said.

According to experts, PKD is an enzyme-related glycolytic defect that results in red cell hemolysis. The disease can result in hereditary non-spherocytic anemia. Babies with serious PKD can develop anemia upon birth and must depend on blood transfusions to survive. So far, the treatments include blood transfusions and spleen removal surgery, while many sufferers show no effects from the treatments.

"Gene replacement therapy is a novel treatment, which uses the technique to recognize and remove the faulty gene, apply a piece of DNA in its correct form to repair the gene by the CRISPR genome editing technology and then transfuse the stem cells with normal genes back to the patient," said Dr Chen Jing, a leading expert in the therapy. "The treatment can help patients to regain a proper haemotogenous function without risk from stem cells donated by other people. It is a more effective and safer treatment.

"For patients with serious PKD and have no effects in blood transfusion and spleen removal, stem cell transplant from a donor is the only cure. But the treatment is limited by a difficulty in finding a matched donor and transplant-related complications. The gene therapy provides new hope," she said.

Two patients have currently undergone the investigator-initiated clinical research, and researchers plan to apply for registered clinical trials for global patients.

Interested sufferers of the disease can contact the doctors through qinxia@scmc.com.cn for a consultation.