In this individual (the first to receive gene therapy in the United States for a genetic form of hearing loss) hearing was restored across all tested frequencies (achieving thresholds of 65 to 20 dB HL) and within the normal hearing range at some frequencies at the Day 30 visit. The company noted that both the surgical administration procedure and the investigational therapy were well tolerated, and no serious adverse events were reported.
“Gene therapy for hearing loss is something physicians and scientists around the world have been working toward for over 20 years,” said John Germiller, MD, PhD, attending surgeon and director of clinical research in the division of otolaryngology at Children’s Hospital of Philadelphia, and a principal investigator of the AK-OTOF-101 clinical trial who administered AK-OTOF to this participant. “These initial results show that it may restore hearing better than many thought possible.”
Akouos was co-founded by Manny Simons, PhD, the company’s CEO, in 2016. The company’s two leading programs are the first two inner ear AAV programs to enter clinical development. AK-OTOF is an AAV gene therapy for the restoration of hearing in individuals with a genetic sensorineural hearing loss due to mutations in the otoferlin gene. The otoferlin gene is expressed in the sensory cells that are found in the inner ear and that convert sound-driven fluid waves into neural signals.
To date, there has never been a single drug or biologic approved for direct inner ear administration. The inner ear is not easy to access. It is closer to the brain than the middle ear, and the sensory cells are encased in a fluid-filled, bony structure.
AK-OTOF (AAVAnc80-hOTOF) is a dual adeno-associated viral (AAV) vector-based gene therapy designed to restore auditory function by gene transfer and durable expression of normal, functional otoferlin protein to the inner hair cells of the cochlea. AK-OTOF utilizes AAVAnc80, a capsid with high transduction efficiency for inner hair cells, together with a strong ubiquitous promoter to achieve expression of otoferlin, observed only in the target inner hair cells, at levels that have the potential to restore high acuity physiologic hearing.
Simons told GEN in 2022 that AAV gene therapies are “ideally suited to the inner ear.” AAV vectors can be delivered directly without exposure to the rest of the body, allowing a high ratio of vector to contact the target cells. Also, the hair cells don’t divide, which means the expression of functional genes may be sustained over the long term.
In the AK-OTOF-101 trial, participants receive a single, unilateral intracochlear administration of AK-OTOF. Participants in cohort 1 receive AK-OTOF at a dose of 4.1E11 total vector genomes.
The Akouos delivery device, being developed in parallel specifically for intracochlear administration, enables a minimally invasive surgical approach to deliver AK-OTOF throughout the cochlea.
These results, including initial data from a second participant to receive AK-OTOF, will be presented during the Late Breaking Presidential Symposium at the 2024 Association for Research in Otolaryngology (ARO) MidWinter Meeting.
https://www.genengnews.com/topics/translational-medicine/gene-therapy-restores-hearing-in-11-year-old-after-just-one-month/
Check out our AAV CDMO service to expedite your gene therapy research
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
Related News
Exploring Tau Protein’s Role in Glaucoma: New Insights and Therapeutic Potential
Glaucoma, a chronic neurodegenerative disorder, leads to irreversible vision loss by damaging retinal ganglion cells (RGCs) and the optic nerve, often associated with increased intraocular pressure (IOP). Despite the benefits of IOP-lowering treatments, the underlying...
FDA-mandated CAR-T monitoring period could be halved, say researchers
In patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL), the two hallmark post-chimeric antigen receptor (CAR)-T therapy toxicities are extremely rare after two weeks, supporting a shorter, more flexible toxicity monitoring period, according to a study...
Ancestral CRISPR-Cas13 Ribonucleases Discovered: Implications for Genome Editing
In a pioneering study published in *Science*, a team of researchers led by Peter H. Yoon and Jennifer A. Doudna from the University of California, Berkeley, has made a remarkable discovery in the realm of CRISPR technology. The team has identified an ancestral clade...
KBI Biopharma Expands Manufacturing Contract with Global Pharmaceutical Company
KBI Biopharma Inc., a JSR Life Sciences company and global cGMP contract development and manufacturing organization (CDMO), has extended and expanded its manufacturing contract with a leading global pharmaceutical company. Originally initiated in 2020, the renewed...
Related Services
Plasmids GMP Services
AAV GMP Services
