Leverage the innovative treatment of genetic eye diseases China's first clinical research on "congenital black eye" gene therapy has begun

There are more than 500,000 forgotten blind people in China, some of whom may become blind in their twenties and thirties, and some of whom will become blind by the age of fifty or sixty. This group of "forgotten blind people" is a patient with hereditary retinal disease. Due to the lack of effective interventions, it has long been called "incurable" eye disease. The cost of gene therapy approved for listing internationally is often nearly one million US dollars, which makes many patients prohibitive. Now, this conundrum has finally been leveraged. Recently, the "National Team" of Clinical Research on Eye Diseases in China and the Ophthalmology Center of Shanghai First People's Hospital (National Clinical Medical Center for Eye Diseases) have opened the first clinical research on gene therapy for "congenital black eye" in China.

This means that the domestic independent research and development of new drugs for gene therapy ophthalmology has entered the "transformation fast lane", which is expected to fill the gap in the field of independent research and development of gene therapy drugs in China while bringing bright hope to blind people with hereditary eye diseases.

Xiao Yi (pseudonym) from Zhengzhou, Henan Province, is only 11 years old this year, but he is already an "old patient" with a 10-year history of hereditary retinal disease. At the age of 1, Xiao Yi's father discovered the child's abnormality. "When she learns to walk, she often wrestles, especially at night, it seems that she can't see anything." For Xiao Yi, there are only 8 to 10 hours a day, and as soon as the sun goes down, the colorful world in her eyes will disappear. It is understood that patients with hereditary retinal diseases carry disease-causing mutant genes, resulting in damage to the function of retinal nerve cells or even complete death. Because nerve cells cannot regenerate once they die, the patient's vision will gradually lose with the development of the disease, and conventional treatment methods are basically ineffective for this type of genetic disease. Every family of a patient with a hereditary retinal disease has suffered immensely and has been called the "nightmare of the family."

In December 2017, an ophthalmic gene therapy drug called Luxturna was launched in the United States to treat children and adult patients with specific types of "congenital blackness," but the nearly million dollars in treatment costs became a barrier for the vast majority of patients. In addition, the pathogenic gene mutation spectrum of hereditary eye diseases in China is different from that of foreign countries, and some of the more concentrated pathogenic genes and mutation hotspots have the characteristics of Mutation in China, making the target drugs developed abroad not fully applicable to domestic patients.

Therefore, it is imperative to explore the mutation hotspots of the Chinese people, and to develop precise treatment technologies for the characteristics of hereditary eye diseases of the Chinese people, and to build an efficient and high-quality gene therapy technology platform. As the supporting unit of the National Clinical Medical Center for Eye Diseases, the research team of the Ophthalmology Center of Shanghai First People's Hospital relies on the Shanghai Engineering Research Center of Ophthalmology and the Shanghai Key Laboratory of Ophthalmology, and jointly undertakes this task.

Explore genetic drugs suitable for Chinese people

Gene drug therapy was conceived from a very familiar and unfamiliar organism, the virus. "Recombinant adeno-associated virus" (AAV) as a therapeutic gene delivery carrier, it does not have the usual viral pathogenic effect, will not self-replication cause transmission, bioengineered it can carry the gene fragment of interest into the cell due to genetic mutation and affect the function, there for functional repair. This operation is applied in eye diseases, requiring not only the safety of the drug itself, but also the extremely exquisite skill of the operator - the precise injection of the drug into the retinal tissue only 0.3 mm thick by surgery, comparable to the micro-carving on the hair.

The research team selected and optimized specific AAVs, forming a "pseudovirus" that carries the normal RPE65 gene and specifically identifies the diseased cells, the retinal pigment epithelial cells, like an internal factory that begins to continuously produce the RPE65 protein that patients lack. Gene drugs are characterized by "one injection, long-term expression", and the imported drugs continuously express the RPE65 protein with normal function in RPE cells.

In June 2021, after detailed examination, strict evaluation and screening, clinical research and exploration officially began, and Xiaoyi became the youngest of the first six volunteers enrolled in the group. On September 16, 2021, Xiao Yi received a subretinal injection in his right eye. On December 16, 3 months after receiving the injection, Xiao Yi's review results showed that the right eye was in good condition, and his vision increased from the original 9 letters to 47 letters, and what was more gratifying was that Xiao Yi's dark vision was greatly improved. In addition to Xiao Yi, the other 5 enrollees also had different degrees of significant improvement in their vision after treatment.

Wang Hong, head of the shanghai ophthalmology gene therapy research team and deputy director of the Department of Ophthalmology, said that the future challenges are still very large, there are hundreds of gene therapy sites, and now it is just a good start, and it needs to be continuously explored in order to truly let this part of the "forgotten blind people" see the light again.

It is reported that China's first congenital black eye "LX101" drug used to carry out clinical research in the early stage has submitted a clinical research communication application for gene therapy new drugs to the Drug Evaluation Center of the State Drug Administration, and if successfully approved, this will be the first clinical trial application for new drugs for gene therapy submitted in China. Its significance is far more than expected to enable more patients with congenital nibble to get rid of blindness, but also means that China already has the conditions to build a clinical research system for gene therapy, opens up the industrial closed loop of biomedical research and development - production - clinical application, and has a demonstration and promotion effect on gene therapy for other diseases.

Text, photo/Guangzhou Daily, New Flower City Reporter: Zhou Yufei

Guangzhou Daily New Flower City Editor: Zhou Yufei