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A recent clinical study has shown that gene therapy can restore hearing function, allowing five children with congenital bilateral deafness caused by genetic mutations to regain their ability to hear.
DNA, RNA, molecular biology, genetic manipulation, and more recently gene therapy: so many words are coming to the forefront, and drawing a lot of attention but most importantly, big hopes. And for good reason! But what exactly is gene therapy? Can we truly treat diseases by manipulating a patient’s DNA? This field of research, which has now become a medical practice, has considerably evolved over the past few decades. What once seemed like pure science fiction is now a tangible reality, thanks to technological breakthroughs and a better understanding of human genetics. Gene therapy is thus a groundbreaking approach aimed at treating and potentially curing diseases by directly modifying the genetic code, and thus the patients’ DNA. In practice, it involves introducing a healthy gene into a patient’s cells to replace or correct a defective gene responsible for a genetic disease (such as spinal muscular atrophy—a rare neurological genetic disorder leading to severe muscle weakness and eventually muscle atrophy) or an acquired condition (such as cancer or neurodegenerative diseases). As such, this therapeutic strategy offers new prospects for treating diseases that were once deemed incurable.
Proof of Concept
“Innovative therapies have now become a key component of treatment for several conditions, including hereditary and rare diseases,” says Professor Salima Hacein-Bey-Abina, a leading pioneer in gene therapy, in an exclusive interview with This is Beirut. In 2000, alongside Professor Alain Fischer, she achieved a historic breakthrough by using gene manipulation to correct severe combined immunodeficiency in “bubble babies,” children with a critical genetic disorder and nearly nonexistent immune systems. This accomplishment was the first major global success of gene therapy. “More recently, this therapeutic approach has entered the field of cancer, with the emergence of cellular immunotherapies such as genetically modified T lymphocytes, known as CAR-T cells, which are currently used as a second-line treatment for certain hematological cancers,” explains the French researcher. She concludes, “Given these proofs of concept, gene therapy applications are set to gradually expand to other conditions.”
Congenital Deafness
Recently, a gene therapy clinical trial successfully restored hearing in five children aged between 2 and 11 years, who were affected by a form of congenital bilateral deafness caused by mutations in a gene called OTOF. This gene is crucial for producing otoferlin, a protein essential for transmitting auditory information to the brain. According to the results published on June 5 in Nature Medicine, all patients showed improvements in hearing function and speech, along with restored sound localization abilities. “Bilateral hearing is known to improve speech recognition in noisy environments and is essential for better music perception, sound localization, and greater overall satisfaction in daily life,” note the authors of the Chinese study, who previously conducted a clinical trial on single-ear deafness. The results of that initial trial were published in January 2024 in The Lancet.
The recent study is an interim analysis of a single-arm trial (where all patients received the same treatment being tested), conducted over a period of 13 or 26 weeks at the Eye and Ear Hospital of Fudan University in Shanghai, China. The researchers injected functional copies of the human OTOF gene into both inner ears of the patients using a specialized, minimally invasive surgical procedure. During the follow-up period, 36 adverse effects were recorded, but no serious events were reported. The trial is ongoing with continuous monitoring of the participants. So far, the results seem mostly promising: “Two patients were able to enjoy music 13 to 15 weeks after receiving gene therapy, as demonstrated by their dancing while listening to music,” the scientific publication reports.
Genetic Screening
These results provide the first proof of concept that gene therapy is viable, safe, and effective for this type of genetic deafness. They pave the way for extending this therapeutic strategy to hereditary deafness caused by other genes. “For children with congenital hearing loss, we recommend universal genetic screening to enable early intervention,” conclude the Chinese researchers. According to the World Health Organization, more than 5% of the global population, or 430 million people, suffer from hearing loss, including 34 million children. Furthermore, around 26 million people experience congenital hearing loss, with 60% of these cases due to genetic factors. Pathogenic mutations in the OTOF gene account for 2 to 8% of hereditary deafness cases.
