Children’s Hospital of Philadelphia (USA) corrected genetic hearing loss using a gene therapy procedure developed in Italy. An 11-year-old kid with a rare type of congenital deafness has been able to hear for the first time thanks to a gene therapy method created by an Italian team. A team at the Children’s Hospital of Philadelphia in the United States produced the world-first result, which expands upon the work of Alberto Auricchio’s team at TIGEM Telethon Institute of Genetics and Medicine in Pozzuoli.
Defects in the OTOF gene, which codes for otoferlin and is one of the more than 150 genes known to cause deafness in humans, are the source of the boy’s condition. Gene therapy has the potential to replace a malfunctioning gene with a functional one. Genes are often carried by small viral vectors like adeno-associated viruses (AAV), however huge genes like OTOF are too large for the virus, which is unable to carry long DNA sequences.
The gene might be divided into two parts that could each fit on a single viral vector and then reconstruct inside the patient’s cells, according to the researchers in Naples. Additionally, the scientists added recombinant gene sequences to the vectors to direct the union of the two halves and splicing signals to aid in the subsequent removal of extraneous sequences. The procedure could guarantee that the patient’s body produces the required protein.
For the past ten years, the Italian team has been developing novel gene therapy systems, mostly focusing on treating uncommon eye conditions. Note, that there is currently no therapy for this condition, and patients are deaf and blind from birth. After receiving approval from the Italian drug agency, the researchers plan to begin retinitis clinical trials at the University Hospital in Naples in the coming months. The most prevalent kind of inherited macular dystrophy, Stargardt’s disease, is another project the organization is focusing on.
While looking for funding for the retinitis pigmentosa trial — which has now been granted by the Sofinnova investment fund and the Telethon Foundation — Auricchio’s team had licensed the technology to the American company Akous, a biotech company owned by Ely Lilly. That company then partnered with John Germiller’s team at the Children’s Hospital in Philadelphia to experiment with gene therapy for deafness.
Last October, they performed surgery on the 11-year-old to deliver a gene therapy based on Italian system into his inner ear by an endoscope. The boy went from total deafness to mild hearing loss after four months, and the team notes that he can now hear voices and background noise. There is a larger clinical trial going on in several hospitals.
Source: https://doi.org/10.1038/d43978-024-00032-3