First gene therapy treatment for a hereditary form of deafness in the USA
Jan 26, 2024
The Children's Hospital of Philadelphia announced the treatment with an experimental gene therapy for a hereditary form of deafness in an 11-year-old boy - the first time this has ever happened in the United States. This treatment was described in an article in the New York Times. The form of hereditary deafness in question is due to variants in the gene coding for otoferlin, one of more than 150 genes known to date to cause deafness in humans. According to the hospital's official statement, “almost four months since receiving the investigational gene therapy in one ear, the patient's hearing has improved enough that he now has only mild to moderate hearing loss in the ear that was treated. The patient is literally hearing sound for the first time in his life. He can hear his father's voice, the sound of a car passing by and even the scissors clipping his hair.”
This is important news for the novel possibilities it offers, and it also makes Telethon proud: the dual vector technology used, in fact, has benefited from the work of Alberto Auricchio's group, head of the Molecular Therapies programme at the Telethon Institute of Genetics and Medicine (Tigem) and full professor of Medical Genetics at the 'Federico II' University of Naples. Auricchio has been working for many years to try to overcome one of the 'practical' limits of gene therapy, that of the capacity of viral vectors. This obstacle has limited the application of gene therapy in those diseases associated with large genes: while scientists have learnt to turn certain viruses into vectors for therapeutic gene transfer, they have very often come up against a limitation of bulk. Auricchio’s research as always focused on adeno-associated vectors (AAVs), among the most widely used in the clinical field today, and it is precisely on these vectors, for example, that the world's first approved gene therapy drug for a hereditary form of blindness or the experimental gene therapy for mucopolysaccharidosis type 6 developed in Tigem's laboratories are based.
To try to overcome this capacity problem, starting in 2012, thanks to the support of Telethon and competitive funds such as those made available by the European Research Council (ERC), Auricchio and his team developed two platforms (the 'Dual Hybrid' system and the intein-based system, described in the figure below) that is designed to allow the genetic material load to be split into several viral vehicles and then form the complete therapeutic protein in the cell.
This dual hybrid system is licensed to Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company, a precision genetic medicine company focused on developing gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for people worldwide who live with hearing loss. With this dual system, a cell is exposed to two vectors carrying two different portions of the therapeutic gene and sequences that allow the two portions to recombine in the cell, reforming the gene in its entirety.
Confirming the value of this and other technological platforms developed at Tigem are the numerous European investments, in particular those of the European Research Council (ERC), and subsequently the substantial industrial capital from the Sofinnova-Telethon fund, which in 2021 gave sight to the start-up AAVAntgarde Bio, and three major international investment companies (Atlas Venture, Forbion and Longwood) in 2023.
There are at least a thousand large disease genes that are not currently 'packable' in current vectors, and several hundred genetic diseases that could potentially benefit from multi-vector systems.: The hope is therefore that these technologies will open the door to gene therapy for an ever-widening number of diseases, and the news that has just arrived from Philadelphia bodes well.
The Children's Hospital of Philadelphia announced the treatment with an experimental gene therapy for a hereditary form of deafness in an 11-year-old boy - the first time this has ever happened in the United States. This treatment was described in an article in the New York Times. The form of hereditary deafness in question is due to variants in the gene coding for otoferlin, one of more than 150 genes known to date to cause deafness in humans. According to the hospital's official statement, “almost four months since receiving the investigational gene therapy in one ear, the patient's hearing has improved enough that he now has only mild to moderate hearing loss in the ear that was treated. The patient is literally hearing sound for the first time in his life. He can hear his father's voice, the sound of a car passing by and even the scissors clipping his hair.”
This is important news for the novel possibilities it offers, and it also makes Telethon proud: the dual vector technology used, in fact, has benefited from the work of Alberto Auricchio's group, head of the Molecular Therapies programme at the Telethon Institute of Genetics and Medicine (Tigem) and full professor of Medical Genetics at the 'Federico II' University of Naples. Auricchio has been working for many years to try to overcome one of the 'practical' limits of gene therapy, that of the capacity of viral vectors. This obstacle has limited the application of gene therapy in those diseases associated with large genes: while scientists have learnt to turn certain viruses into vectors for therapeutic gene transfer, they have very often come up against a limitation of bulk. Auricchio’s research as always focused on adeno-associated vectors (AAVs), among the most widely used in the clinical field today, and it is precisely on these vectors, for example, that the world's first approved gene therapy drug for a hereditary form of blindness or the experimental gene therapy for mucopolysaccharidosis type 6 developed in Tigem's laboratories are based.
To try to overcome this capacity problem, starting in 2012, thanks to the support of Telethon and competitive funds such as those made available by the European Research Council (ERC), Auricchio and his team developed two platforms (the 'Dual Hybrid' system and the intein-based system, described in the figure below) that is designed to allow the genetic material load to be split into several viral vehicles and then form the complete therapeutic protein in the cell.
This dual hybrid system is licensed to Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company, a precision genetic medicine company focused on developing gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for people worldwide who live with hearing loss. With this dual system, a cell is exposed to two vectors carrying two different portions of the therapeutic gene and sequences that allow the two portions to recombine in the cell, reforming the gene in its entirety.
Confirming the value of this and other technological platforms developed at Tigem are the numerous European investments, in particular those of the European Research Council (ERC), and subsequently the substantial industrial capital from the Sofinnova-Telethon fund, which in 2021 gave sight to the start-up AAVAntgarde Bio, and three major international investment companies (Atlas Venture, Forbion and Longwood) in 2023.
There are at least a thousand large disease genes that are not currently 'packable' in current vectors, and several hundred genetic diseases that could potentially benefit from multi-vector systems.: The hope is therefore that these technologies will open the door to gene therapy for an ever-widening number of diseases, and the news that has just arrived from Philadelphia bodes well.