Groundbreaking Gene Therapy for Usher Syndrome Type 1B Administered in Italy: A New Era in Genetic Medicine
The world of genetic medicine has witnessed a monumental breakthrough with the first administration of an experimental gene therapy for Usher syndrome type 1b, a rare hereditary eye disease that is also associated with deafness. This landmark event took place at the University of Campania Luigi Vanvitelli in Naples, Italy, as part of a phase 1/2 clinical trial. The innovative therapy, developed at the Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli, represents a significant leap forward not only for Usher syndrome but potentially for a wide array of other genetic diseases that currently lack effective treatments. By aiming to correct the underlying genetic defect causing the disease, this therapy holds promise for transforming the lives of countless patients who suffer from debilitating genetic conditions.
Gene therapy, at its core, seeks to address the root cause of genetic diseases by providing a functional version of the defective gene through the use of harmless viruses as vectors. While this concept has been applied to various diseases, the field has faced notable limitations, particularly concerning the size of the genes that can be delivered using viral vectors. Traditional vectors are often unable to accommodate large genes, which restricts their applicability to certain conditions. However, researchers at TIGEM have pioneered two groundbreaking platforms that overcome these size constraints, enabling the transfer and subsequent reassembly of large fragmented genes within the body. One such platform, known as ‘dual-aav,’ was employed in the treatment of the first patient with Usher syndrome type 1b, marking a pivotal moment in the evolution of gene therapy.
The administration of the therapy involves injecting the vector directly into the subretinal space of the eye, a procedure that requires precision and expertise. This trial, sponsored by Aavantgarde Bio—a biotech company founded in 2021 as a spin-off of TIGEM—represents the first human application of the dual-aav technology for an ophthalmological indication. The institute’s director, Alberto Auricchio, expressed his excitement and optimism regarding this development, highlighting the potential for positive outcomes in patients. The ultimate goal of this pioneering therapy is to help patients regain visual function, offering a glimmer of hope to those affected by Usher syndrome type 1b and other similar conditions.
This initiative is part of a larger project named Luce-1, which aims to explore the broader applications of the dual-aav technology. The technology has already demonstrated promising results in laboratory studies, providing a solid foundation for its clinical application. The success of this trial could pave the way for future advancements in gene therapy, potentially extending its benefits to a wider range of genetic diseases. By overcoming the size limitations of traditional viral vectors, the dual-aav technology enhances the efficacy of gene therapy, making it a more viable option for treating complex genetic conditions.
Aavantgarde Bio recently announced the initiation of the Luce-1 trial, a phase 1/2 clinical study designed to assess the safety and tolerability of their proprietary dual hybrid gene therapy platform in subjects with retinitis pigmentosa related to Usher syndrome type 1b (USH1b). The dual-aav technology for large gene delivery is the brainchild of Prof. Alberto Auricchio at TIGEM, an internationally renowned research institute based in Naples and managed by the Telethon Foundation. As a spin-off of TIGEM, Aavantgarde holds an exclusive license for the AAV-dual technology for inherited retinal diseases, underscoring the significance of this collaboration in advancing gene therapy research.
The first subretinal gene therapy procedure in the Luce-1 study was conducted under the supervision of Prof. Francesca Simonelli, head of the ophthalmology unit at the University Hospital of Campania Luigi Vanvitelli in Naples. This hospital is one of three clinical sites participating in the phase 1/2 trial, with Prof. Simonelli serving as the global chief investigator. Her involvement as the principal investigator in this first-in-human clinical study of AAVB-081 for patients with retinitis pigmentosa related to USH1b is a testament to her expertise and dedication to advancing patient care through innovative gene therapies.
Prof. Simonelli expressed her enthusiasm for being part of this groundbreaking clinical study, emphasizing the potential to revolutionize the approach to understanding and treating underserved patients with Usher syndrome type 1b. The goal of the Luce-1 trial is to generate robust evidence that will not only advance scientific knowledge but also have a direct impact on patient care. Dr. Jayashree Sahni, Chief Medical Officer of Aavantgarde, echoed this sentiment, highlighting the importance of bringing this potentially novel therapy to the USH1b patient community as swiftly as possible. The collaboration between Aavantgarde and Prof. Simonelli represents a significant step towards achieving this goal.
Prof. Alberto Auricchio, founder and Chief Scientific Officer of Aavantgarde, shared his excitement about seeing the dual hybrid technology being tested clinically in an ophthalmology indication. He expressed hope that the years of research invested in developing this technology would prove its value in addressing the high unmet needs of patients with Usher syndrome type 1b. The involvement of Prof. Simonelli, with her extensive experience and expertise in gene therapy for ophthalmological conditions, is expected to be invaluable in ensuring the successful development and implementation of this therapy.
AAVB-081, the gene therapy product being evaluated in the Luce-1 trial, is an intra-retinal AAV8-based dual hybrid product specifically targeting myo7a-associated Usher syndrome (USH1b). This innovative therapy utilizes two AAV8 vectors, each containing half of an expression cassette encoding for the myo7a gene. Once inside the cell nucleus, the two halves combine to generate therapeutically meaningful protein levels, as demonstrated in animal models. This approach addresses the challenge of delivering large genes, which has been a significant hurdle in the development of effective gene therapies for complex genetic diseases.
Usher syndrome type 1b is an inherited disease that affects both the retina and the inner ear, leading to progressive vision and hearing loss. It is estimated that approximately 20,000 patients in the United States and European Union are affected by this condition. Currently, there are no effective treatments available for Usher syndrome type 1b, making the development of AAVB-081 a beacon of hope for those affected. Aavantgarde’s technology offers a potential solution to the challenge of delivering large genes to patients, providing a new avenue for treatment and improving the quality of life for individuals with this debilitating condition.
The potential impact of this gene therapy extends beyond Usher syndrome type 1b. The dual-aav technology developed by TIGEM and utilized by Aavantgarde represents a significant advancement in the field of gene therapy, with the potential to be applied to a wide range of genetic diseases. By overcoming the size limitations of traditional viral vectors, this technology opens up new possibilities for treating conditions that were previously considered untreatable. The success of the Luce-1 trial could pave the way for further developments in gene therapy, ultimately leading to improved outcomes for patients with various genetic disorders.
As the Luce-1 trial progresses, the scientific community and patient advocacy groups are closely monitoring its outcomes. The collaboration between TIGEM, Aavantgarde, and the University Hospital of Campania Luigi Vanvitelli represents a model for how academic research institutions and biotech companies can work together to advance medical science and improve patient care. The dedication and expertise of the researchers and clinicians involved in this trial are crucial to its success, and their efforts are poised to make a lasting impact on the field of genetic medicine.
In conclusion, the administration of the first experimental gene therapy for Usher syndrome type 1b in Italy marks a significant milestone in the field of genetic medicine. The innovative dual-aav technology developed by TIGEM and implemented by Aavantgarde Bio offers new hope for patients with this rare hereditary eye disease and other genetic conditions. The Luce-1 trial represents the beginning of a new journey for gene therapy, with the potential to transform the lives of countless individuals affected by genetic diseases. As the trial continues, the scientific community eagerly awaits the results, which could pave the way for future advancements and bring us closer to a world where genetic diseases are no longer a barrier to a healthy and fulfilling life.