Science & Pipeline

Deafness is a very common affliction, with more than 300 million people affected worldwide with vast personal, social and economic implications.

Almost 90% of cases are sensorineural in nature, involving the loss of hair cells and/or their associated otic neurons. These are the key cells of the inner ear -the sensory hair cells detect the sound and the otic neurons conduct the signals to the brain. These cells are only produced during the development in utero, your complement at birth have to last a lifetime. If these cells are damaged, they are lost for good and permanent hearing loss ensues.

Hearing loss therapeutics is an exciting field emerging from recent advances in our understanding of inner ear biology but significant complexities and challenges in interacting with the hearing loss condition(s) means that there are still no approved pharmacological treatments for hearing loss.

auditory neuropathy
NEED

Of all the forms of deafness, auditory neuropathy is of particular concern. Auditory neuropathy is a form of sensorineural deafness specifically affecting the conduction of the nerve impulse from the cochlear hair cells to the auditory centres of the brain.

This condition, defined primarily by damage to the auditory neurons with relative preservation of the hair cells, is responsible for a substantial proportion of patients with hearing impairment. While the loss of hair cells can be circumvented partially by a cochlear implant, no routine treatment is available for sensory neuron loss since poor innervation clearly limits the performance of an implant.

Given the absence of an endogenous regenerative response, the use of an external source for cell replacement is a viable concept in hearing loss therapeutics. Rinri’s approach is to utilise the power of pluripotent stem cells in a ‘cell replacement’ therapeutic strategy in which a functioning auditory nerves are regenerated by transplanting appropriate cells to replace and recover the damaged sensory circuitry and restore hearing.

cell therapy
CUTTING EDGE

For our cell therapy approach to work, there is a need for a reliable, renewable source of human progenitors, with the ability for sensory replacement.

Hair cell-like phenotypes and sensory neurons, with different degrees of functional maturation, have been obtained from stem cell populations but none have demonstrated evidence of functional recovery. The cause was our impaired understanding of the molecular events involved in normal human auditory development.

auditory biology
INFORMED

Rinri has capitalised on its unique deep understanding of auditory biology to build developmentally informed protocols to produce pluripotent cell-derived auditory neurons that match natural cochlear phenotypes and functional physiological characteristics.

progenitor cells
FUNCTIONAL

Under the right laboratory conditions, we have shown that our progenitor cells are able to mature into functional auditory neuron cells which exhibit the same morphology and electrophysiology as native cells of the inner ear.

neural connections
RESTORATIVE

Our preclinical studies have clearly demonstrated that when we deliver our cells to the cochlear they survive, engraft, mature and re-establish neural connections to auditory hair cells and wider auditory neural architecture. In models of auditory neuropathy these cells result in a reversal of hearing loss and a 40% improvement in the hearing threshold.

cell therapy for hearing loss
CLINICAL

Following our ground-breaking proof of concept data, significant progress has been made to refine and optimise our technology improving yield, efficiency, potency and purity to the levels required to start the pioneering journey towards first in man clinical trials and to ultimately realise the potential of cell therapy for hearing loss.

PUBLICATIONS

Chen et al. (2009). Human Fetal Auditory Stem Cells Can Be Expanded In Vitro and Differentiate Into Functional Auditory Neurons and Hair Cell-Like Cells. Stem Cells. 27: 1196-1204

https://doi.org/10.1002/stem.62

Nature com

Chen et al. (2012). Restoration of auditory evoked responses by human ES cellderived otic progenitors. Nature. 11; 490(7419). 278-282.

https://doi.org/10.1038/nature11415