Sensorineural hearing loss in humans, caused by degeneration of the sensory hair cells of the inner ear, is not a recoverable injury. Mammalian hair cells do not regenerate like many other cell types. A collaboration between Kevin Ohlemiller, PhD, and a private biotech company hopes to change that.
In 2015, a new start-up, Frequency Therapeutics, was establishing its research program. Co-founder Will McLean, PhD, sought to investigate a variety of test compounds for their ability to promote sensory hair cell regeneration in mice and eventually human subjects.
The Ohlemiller lab has long studied hearing loss models in mice, and offered Frequency a collaborative opportunity to study the effects of their compounds in vivo. Since teaming up with Frequency Therapeutics in 2015, Dr. Ohlemiller has brought his expertise in hearing mouse models and functional hearing testing to bear on this exciting new effort in regenerative medicine.
Now a clinical-stage biotechnology company, Frequency has worked with the Ohlemiller lab for nearly five years to investigate the effects of several regenerative compounds across a variety of mouse hearing loss models. Most importantly, the lab has provided auditory neurophysiological testing to help the company with their mission to select and develop drugs to restore hearing to patients with sensorineural hearing loss.
The collaboration began with trials of compounds locally applied to the ears of mice that had been exposed to noise. Over time, that work expanded to testing transgenic hearing loss models and chemical induced hearing loss models, and the physiological data collected has become more extensive.
The Ohlemiller lab has also conducted cochlear pharmacokinetic (PK) studies in mice. The PK work was eventually expanded to include Alec Salt, PhD, for sampling cochlear fluids in guinea pigs and PK computer modeling for humans. Research technicians currently working on the project include Jaci Lett and Bobby Voss in the Ohlemiller lab, and Jared Hartsock in the Salt lab.
“We are seeing some improvements in auditory brainstem response (ABR) thresholds, a functional test of hearing sensitivity,” says Ohlemiller. “And, we are seeing increases in sensory hair cell numbers after treatment with Frequency’s candidate regenerative compounds.”
“Frequency has been collegial and a pleasure to work with from the start,” says Ohlemiller. “We are involved in all decisions that bear on our contributions, and we will co-author any papers that result from this work. This work has also required me to expand my own skill set in ways that have promoted other collaborations.”
The compounds that Dr. Ohlemiller and Frequency have been studying recently completed a phase I/II clinical trial to test safety and effects on hearing in patients with stable sensorineural hearing loss.
“The work Dr. Ohlemiller has conducted has been important to our studies and our ability to select and move compounds into the clinic,” says Dr. McLean.
The results of the trial showed that the compounds had no adverse events, and a number of patients demonstrated hearing improvement.
“We saw very promising results from our therapeutic treatment, particularly in improving speech intelligibility performance,” Dr. McLean said. “We feel that these compounds have the possibility to help the millions of patients around the world with sensorineural hearing loss.”
The Ohlemiller lab and Frequency plan to continue their drug discovery collaboration to identify treatment candidates for hearing restoration.