Gene-Correction Therapy Improves Hearing Loss by 10 Times

Having talked recently with someone that is very well informed of the research on the fighting deafness front, due to his personal hearing problems, he mentioned that gene therapy is right now the only way that he sees as credible in the long term. Having said that, I do not have any personal opinion on the matter, since I am just a layman, but these are some promising articles I could find with a quick google search for anyone interested.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796998/
https://www.sciencedaily.com/releases/2020/12/201223125732.htm
https://www.fiercebiotech.com/biote...to-push-hearing-loss-gene-therapy-into-clinic

 

It's not entirely on-topic, but there's promising news that a new gene therapy technique could help people with Parkinson's and perhaps (in my opinion) also for people who suffer from non-pulsatile tinnitus, since many researchers point toward overactive neurons as key actors in the manifestation of this particular 'brain circuit disorder' (for lack of a better term).

Gene Therapy Targeting Select Brain Cells May Treat Parkinson’s | Therapy Switches Off After Targeting Overactive Neurons | Parkinson's News Today (Maia, 2022)

UK team reports that therapy switches off after calming overactive neurons

A gene therapy designed to track down and keep overactive brain cells in check was able to lower the number of seizures in a mouse study of epilepsy. This therapy is also notable in sparing healthy brain tissue by switching itself off after its work is done.

Should early work continue to show promise and it move into testing in people, the gene therapy might be used to treat other neurological diseases marked by specific brain cells altered in pathological, or disease related, ways, including Parkinson’s.

“This approach can be used to treat important neuropsychiatric diseases that do not always respond to medication. The gene therapy is self-regulated and can therefore be used without deciding a priori which brain cells need to be targeted,” Dimitri Kullmann, MD, PhD, who co-led the study, said in a university press release. Kullmann is a professor at University College London’s Queen Square Institute of Neurology in the U.K.

‘Self-regulated’ therapy could be used for various neurologic diseases

“Importantly, it could in principle, be extended to many other disorders such as Parkinson’s disease, schizophrenia and pain disorders, where some brain circuits are overactive,” Kullmann added.

The study, “On-demand cell-autonomous gene therapy for brain circuit disorders,” was published in the journal Science.

In the healthy brain, nerve cells work along circuits that allow them to fire electrical signals from one neuron to the next. One circuit can link a number of regions in the brain, which often act together to control functions such as movement.

In Parkinson’s and other neurological diseases, some of the neurons in a circuit can start to wither away and die while others become overly active.

People with these diseases often fail to respond well to medications, or they experience side effects that cause them to stop the treatment.

Gene therapy is seen as a possible treatment approach. But “a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and ‘healthy’ surrounding or intermingled neurons,” the researchers wrote.

To get around this limitation, a team at University College London developed a gene therapy approach that quenches neuronal firing only for as long as brain cells are overactive.

“We invented a gene therapy that switches on only in overactive cells, and switches itself off if activity returns to normal,” said Gabriele Lignani, PhD, the study’s co-lead scientist.

The team placed the KCNA1 gene, which provides instructions for making part of a potassium channel called Kv1.1, under the control of a cfos promoter— a DNA sequence that’s switched on by intense neuronal firing. The flow of potassium ions into and out of neurons regulates their ability to pass along electrical signals. Kv1.1, in particular, transports potassium ions into neurons and reduces neuronal firing.

When packaged in a harmless viral vector for delivery into seizure-prone mice, the gene therapy calmed the brain cells that became overactive after a seizure was triggered. A seizure is a burst of uncontrolled electrical activity between brain cells.

The therapy also prevented spontaneous seizures from occurring, cutting their number by about 80% while leaving the animals’ behavior and cognitive function unaffected, the researchers reported.

“By re-directing this activity-sensing mechanism to drive the production of molecules that stop brain cells from firing, we showed that epileptic seizures can be suppressed,” Lignani said.

Similar observations were seen in miniature brains, a model created by growing skin-derived human stem cells in a lab dish.

Study results show that “activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders,” the researchers concluded.

 

Lol, it's not like you have the opportunity of using rodents; you HAVE TO to use rodents. Dr. Rauschecker lamented (which interview was it?), considering primates much preferable to rodents, how there are way too many obstacles even in getting "a geriatric monkey" from the zoo. It's really preposterous how these regulations are contributing to prolonging our suffering.

 

Regarding tinnitus, I think this is absolutely a term we should seriously think of adopting.

 

I'd rather have cancer.

 

Good! How many years do our lives still need to be on hold? When will this therapy be available? Once again in "5-10 years'"?

 

Can we just get rid of the FDA and red tape for this one project, please?!

 

If it's dignity you're yearning for, you can just lie to people that you have cancer, and folks'll consider you 'strong' and a 'fighter'. Imagine if people told cancer patients "you're so sensitive", and "don't be a drama queen!" for calling in sick from work.

 

I know from a smart friend of mine, this kind of treatment will help with epilepsy, but not with tinnitus, which has different potassium channels involved.

So this is useless for tinnitus sufferers.

 

Honestly, that's a tough nut to crack for an average Joe like me. Your friend may have a good point in regards to Kv1.1, aside from that Kv7.2/7.3 also plays a part in the manifestation of both epilepsy and tinnitus. Many research papers have firmly established the role of Kv1.1 in epilepsy, but that's not extensively researched in the case of tinnitus, except that this particular channel does play a fundamental role in auditory processing in the cochlear nucleus (which is part of the brainstem + a part of the auditory pathway).

I've forwarded your question to the author of this paper. Perhaps she could shed some light on this particular matter in regards to tinnitus.

 

Did they clarify the potassium channels involved?

 

What @Christiaan said below is good. Though research can always come up with more, right?

Kv7.2/7.3 are not the main potassium channels targeted by XEN1101?

 

Not to bring up the mice again, but I recall reading they can be ordered by labs with genetic alterations to be born with issues from the get go for testing new ideas.

 

Yes, XEN1101 is a Kv7.2/7.3 potassium channel modulator.

→ Link

 

This would only (hypothetically) help patients with a KNCQ4 mutation, in other words, only those with a genetic predisposition for a specific type of hearing loss.

Link to the published article:

→ In vivo outer hair cell gene editing ameliorates progressive hearing loss in dominant-negative Kcnq4 murine model

 

Are you absolutely sure about that?

 

Read the article.