PharmaLegacy Contributes to World’s First Gene Therapy for Hereditary Deafness

Recently, The Lancet published the world’s first clinical trial study on gene therapy for hereditary deafness. This study has proved the safety and demonstrated the great potential of gene therapy for the treatment of hereditary deafness, which has attracted extensive attention from medical community.

The deafness gene therapy drug RRG-003 (AAV1-hOTOF), used in this study was jointly developed by Eye & ENT Hospital of Fudan University, Harvard Medical School and Shanghai Refreshgene Therapeutics Co., Ltd. This study reported the safety and efficacy of gene therapy with an adeno-associated virus (AAV) serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) as a treatment for children with autosomal recessive deafness 9.

Preclinical studies of this gene therapy were published in November 2023 in Molecular Therapy-Methods & Clinical Development. PharmaLegacy participated in the preclinical safety evaluation of the gene therapy, helping it to smoothly start the IIT study.

PharmaLegacy’s advanced and comprehensive hearing research platform can provide services ranging from early product development to preclinical research, including pharmacokinetic, efficacy, and safety evaluation. The team has extensive experience helping clients all over the globe in their preclinical stage R&D.

Hearing Loss Model

A variety of hearing impairment models can be provided by PharmaLegacy, including noise exposure, chemotherapy drug induction (e.g. cisplatin), aminoglycoside antibiotic induction, transgenic mice, aged mice, and others.

Local Delivery

PharmaLegacy’s hearing team has rich experience in local delivery, and accurately completed the injection without affecting hearing.
Middle ear delivery (1. Transtympanic injection; 2. Bulla ostomy)
Inner ear delivery (3. Round window membrane delivery; 4. Posterior semicircular canal injection; 5. Cochlea ostomy)

Pharmacokinetic (PK) Studies

PharmaLegacy provides drug PK laboratory services, including local PK (Perilymph collection).

Auditory Function Evaluation

PharmaLegacy has multiple sets of hearing test system that provide high-throughput auditory brainstem response, ABR) and distortion product otoacoustic emissions (DPOAES).

Cochlear Explants & SGNs Culture

PharmaLegacy provides isolation, culture, and drug evaluation in newborn animals of cochlear explants and spiral ganglion neurons (SGNs).

Lab Animals for Hearing Studies

PharmaLegacy conducts hearing studies in mice, rats, guinea pigs, and non-human primates.

Ex vivo Assays

A variety of ex vivo assay services are available, including cochlear implants, frozen/paraffin sections, immunofluorescence and immunohistochemistry.

PharmaLegacy’s confocal imaging platform (Nikon AX laser confocal microscope) can fully meet various requirements for high-quality imaging.

References:

  • Lv J, Wang H, Cheng X, et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet. Published online January 24, 2024.
  • Zhang L, Wang H, Xun M, et al. Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates. Mol Ther Methods Clin Dev. 2023; 31:101154.
  • Fang QJ, Wu F, Chai R, Sha SH. Cochlear Surface Preparation in the Adult Mouse. J Vis Exp. 2019; (153):10.3791/60299.
  • https://mp.weixin.qq.com/s/foSOaFxOhIvYRxXT09DCLA