Complete Restoration of Hearing Loss and Cochlear Synaptopathy

[streifzug]

Complete Restoration of Hearing Loss and Cochlear Synaptopathy via Minimally Invasive, Single-Dose, and Controllable Middle Ear Delivery of Brain-Derived Neurotrophic Factor–Poly(dl-lactic acid-co-glycolic acid)-Loaded Hydrogel

Abstract
Noise-induced hearing loss (NIHL) often accompanies cochlear synaptopathy, which can be potentially reversed to restore hearing. However, there has been little success in achieving complete recovery of sensorineural deafness using nearly noninvasive middle ear drug delivery before. Here, we present a study demonstrating the efficacy of a middle ear delivery system employing brain-derived neurotrophic factor (BDNF)–poly-(dl-lactic acid-co-glycolic acid) (PLGA)-loaded hydrogel in reversing synaptopathy and restoring hearing function in a mouse model with NIHL. The mouse model achieved using the single noise exposure (NE, 115 dBL, 4 h) exhibited an average 20 dBL elevation of hearing thresholds with intact cochlear hair cells but a loss of ribbon synapses as the primary cause of hearing impairment. We developed a BDNF-PLGA-loaded thermosensitive hydrogel, which was administered via a single controllable injection into the tympanic cavity of noise-exposed mice, allowing its presence in the middle ear for a duration of 2 weeks. This intervention resulted in complete restoration of NIHL at frequencies of click, 4, 8, 16, and 32 kHz. Moreover, the cochlear ribbon synapses exhibited significant recovery, whereas other cochlear components (hair cells and auditory nerves) remained unchanged. Additionally, the cochlea of NE treated mice revealed activation of tropomyosin receptor kinase B (TRKB) signaling upon exposure to BDNF. These findings demonstrate a controllable and minimally invasive therapeutic approach that utilizes a BDNF-PLGA-loaded hydrogel to restore NIHL by specifically repairing cochlear synaptopathy. This tailored middle ear delivery system holds great promise for achieving ideal clinical outcomes in the treatment of NIHL and cochlear synaptopathy.

Sounds really promising, doesn't it?

 

[dd314]

This is exactly what OTO-413 was I believe, are there any differences?

 

[HighleyTall]

Unfortunally this will not cure tinnitus.

 

[streifzug]

This is exactly what OTO-413 was I believe, are there any differences?

This seems like a similar approach now that you mention it. Maybe the delivery mechanism is different? I thought it was news

 

[Muggumbo]

Would be great if this worked in human trials.

 

[Nick47]

Some questions:

1) It's mice, will it translate to humans? Guinea pigs have hearing physiology close to humans, mice less so.

2) This is a BIG ONE for me: how long after noise exposure were the mice treated? If it's within days or weeks, I ain't enthused. Acute vs. chronic is always a big difference.

It ain't that promising to be honest.

 

[Joey Lodes]

Like everything else, hopefully this leads to human trials and eventually a measurable objective treatment for hearing loss.

 

[ColinUK]

Mice again

 

[Street Novelist]

I can't get excited about studies with mice. When they actually inject humans and get the same results, let me know.

 

[Nick47]

Anyone that reads any study on hearing loss or tinnitus MUST ask at least these 2 questions.

1. Were they human subjects?
2. Was the tinnitus or hearing loss chronic?

The study MUST be able to answer yes to both for further interest to be maintained, at least as a patient.

I'm even skeptical of Prof. Thanos Tzounopoulos' work as his studies cannot answer yes to any of the above questions.

 

[BB23]

I'm even skeptical of Prof. Thanos Tzounopoulos' work as his studies cannot answer yes to any of the above questions.

If you have the time, research how antiepileptics benefit epilepsy patients and visual snow syndrome/HPPD sufferers to have an understanding of how these drugs work.

I expect Prof. Tzounopoulos' stuff to be, at best, a good band-aid-like treatment to the actual problem for most, and a permanent reduction for a small group, maybe elimination for even a much smaller group, based on especially what happened with Retigabine use here on Tinnitus Talk.

Similar results are observed with antiepileptic use with visual snow syndrome/HPPD/epilepsy as well.

 

[Stayinghopeful]

It's a big and exciting year for mice with tinnitus.

 

[Joey Lodes]

I feel bad for the mice. Feel free to test on me