They will undertake work on in vivo regenerative medicine approaches in this respect.
Utilizing Mogrify’s cellular reprogramming platform, the partners want to identify the transcription factors involved in cell differentiation to generate new cochlear hair cells, the sensory cells of the auditory system.
Astellas Gene Therapies, a division of Astellas, is covering the research cost of the work as well as contributing its expertise in adeno-associated virus (AAV) based genetic medicine and translational capabilities to complete experiments in pre-clinical models.
Mogrify will exploit its bioinformatic platform, screening, and validation process to characterize potential therapeutic factors.
Astellas' US subsidiary, Astellas Venture Management, was a participant in the Series A for Mogrify in May 2021.
When asked what data supports the idea that the combined platforms could address hearing loss of this nature, Dr Louise Modis, CSO, Mogrify, told BioPharma-Reporter:
"Mechanosensory hair cells are the primary receptors of our senses of hearing and balance. However, as highlighted by Warchol (2011), the mammalian inner ear lacks the regenerative ability to replace lost of hair cells.
"Elucidation of the transcriptional networks and identifying the specific factors regulating hair cell fate determination and differentiation could serve as an approach to regenerate these cells and enable cell replacement therapies for hearing disorders. To date, only a single factor (Atoh1) has been delivered in a clinical trial with inconclusive results.
"Whilst analysis of factor combinations, such as Atoh1, Gfi1 and Pou4f3 by various research groups (Costa et al. (2015); Lyer et al. (2022)), have confirmed the feasibility of inducing hair cells in mouse models, a lack of functional maturity suggests that alternative factors or combinations would be required to produce the desired cell phenotype and subsequent therapeutic effect.
"Utilizing Mogrify’s proprietary direct cellular programming platform and Astellas’ delivery expertise in AAV-based gene therapy, the collaboration will seek to identify novel combinations of transcription factors and deliver these in vivo to generate new cochlear hair cells and address hearing loss."
The alliance, she continued, is looking to validate the effect of identified transcription factors in pre-clinical models. "Based on the results of this collaboration, we would like to hold discussions toward the clinical stage."
An estimated 1.57 billion people globally suffer from hearing loss, and US data suggests that over 10% have severe to profound sensorineural hearing loss in at least one ear, the result of damage to and/or loss of sensory hair cells.
Addressing diseases with high unmet clinical need
Mogrify, founded in 2016, has developed a suite of technologies that utilize a systematic big data approach to direct cellular reprogramming and the maintenance of cell identity.
The biotech's platforms deploy next-generation sequencing, gene regulatory and epigenetic network data to enable the prediction of the transcription factors and optimal culture conditions required to produce any target human cell type from any source human cell type.
The company is leveraging its technology to develop scalable ex vivo cell therapies and in vivo reprogramming therapies for immuno-oncology, ophthalmology and other diseases with a high unmet clinical need.
February 2021 saw Sensorion and Institut Pasteur announce a gene therapy collaboration for hearing loss.