Two Differing Articles on Gene Therapy

I know a lot of people believe that the hope for a cure to our T lies in gene therapy. So I took some time to do a little research on what the scientific community has to say about it. I found two different sites that talk about it in different lights. One I found from the University of Utah Health Sciences which discusses the challenges that gene therapy presents and why it has only had limited success and a good amount of failures. That can be found here:
http://learn.genetics.utah.edu/content/genetherapy/gtchallenges/

The other comes from a science news/magazine site and it talks about gene therapy in a more positive and hopeful light, stating that despite the challenges, gene therapy should be safer now. That can be found here:
http://www.the-scientist.com/?articles.view/articleNo/36481/title/Gene-Therapy-Coming-of-Age-/

I don't know about you but I'm worried that the second article, or articles like it are being a little too optimistic about gene therapy with click bait titles about it being a reality treatment in the near future or that that future is now. What do you guys think? Personally, I'd like to be hopeful but at the same time, I don't want to feel like an idiot if gene therapy gets trashed after awhile of not being able to get it to work.

Of course I do know and have read about the experiences that attheedgeofscience had with gene therapy but as such I don't want to base all my thoughts and hopes off of a few examples and ideas.

 

good articles...
concerning article one, if gene therapy would work for hearing loss, milions could profit and it would be an insane big market.
I know, it's sometimes written very optimistic without telling us about the real long way everything in medicine has to go.
The inner ear is still a mystery, at least it's a snail of nerves. But there are also some advantages, it's well isolated,from other organs and the nerve endings to regenerate are very short (in distance)
So it's theoretical "easier" to regenerate short nerves than longer ones like spinal cord nerves...
I'm positive to see good advances in the next 5 years, it's hope, it's something who let me better learn to live with this devasting conditions of hearing loss and tinnitus....

 

I always relished facts over opinions which is why I ignore all of media.

 

Gene therapy is still in its infancy. I have not heard of any successful clinical trial using gene therapy as its primary therapeutic method.

 

He had stem cell therapy in bangkok and was not from a clinical trial or university, etc. It was just a stem cell treatment not gene therapy. Please do not mix them up.

Gene therapy is where they will take a viral vector and put a piece of the gene that your DNA needs to manufacture a protein into the viral RNA. Then, said virus infects the area (adenovirus) and injects said gene in the RNA into the the DNA via proteins in the cell (transcriptases). So you do nothing with stem cells. However, stems cells could be an approach in the future but is way off.

There are clinical trials for CGF166 in Kansas funded by Novartis but the main research was done by the NIH (a grant from the VA - a lot of vets have hearing loss and T so the US gov did a bit of investment here). Novartis is a big pharma and they also invested in a company called GenVec that made the adenovirus to infect the gene into the cochlea.

So I would be optimistic. There will always be naysayers until we get results. So right now they are only in phase I of testing. The big phase is phase II (efficacy) and that may be in a year or two. Then two more phases and FDA approval.

Of course, as one link you submitted stated, an immunoresponse could neutralize the virus or the gene could get into the wrong tissue. Both of those have been addressed but will need testing during phase I. They actually inject directly into the cochlea so the virus will be more directed to the target tissue. Also the cochlea has immune privilege like they eye. Meaning that an immune response is less likely than other organs. Lastly, it could cause a tumour. But this gene (ATOH1) is actually a suppressive of other oncogenes. Hence, even if it leaks into the brain, it would be a protective gene and not a oncogene.

 

Well CGF166 is in phase I. So far, it has been successful in not causing harm. Phase II will tell us if it is promising. But we of course need to wait to phase IV when the FDA finally approves it. But we are moving fast. Also, if this works, then GenVec will get money from other companies for gene therapy for cancer. The US gov helped GenVec and Novartis but they will use this to spring to other treatments...probably mostly cancer since that is the big payola.

 

The problem regarding supporting cell replacement after they are used up in the gene therapy process is still not solved. Remember this is a treatment for severely hearing impaired. We do not know if this treatment will ever be considered for people who have T and some degree of hearing function. The loss of the supporting cell in the process might also cause a different T for all we know.

 

I'm pretty sure that in phase IV (more open trials) they will have to apply this to subjects that have at least moderate hearing loss...not just severe loss. Otherwise, this probably would not get approved by the FDA. This is a treatment for hearing loss and will go to that market. However, for phase I and II they will probably only test with severe loss, as that is a better group for the initial phases. But to get this approved, they will have to show efficacy at all levels of loss.

Supporting cell replacement seems to not be an issue with Novartis or the FDA. I do agree that if they are lost, you may not get another shot at them again.

I guess it depends on the degree of hearing loss and gain in hearing function. If you have 60dB loss and your T is 20dB in volume, then maybe after getting more hair cells and say you go to 30dB you may still have T but it might be 5dB in volume. So probably you may still have some T but the volume will go way down as more nerve impulses reach the brain. But that is speculation at this point. Maybe some of these subjects in the trials will have T too and can report their loudness if they gain hearing function.

 

Okay thanks for the clarification (please also be aware that I am not a scientist nor do I study the sciences extensively so it is easy for someone like me to mix them up).

 

I'm hopeful for gene therapy. It might need some tweaking but this is pretty monumental that it is already in clinical trials ...with a big pharmaceutical company backing it. There is nothing for stem cells and a hearing loss cure..nothing at all. And all the other "band-aids" that will help with T ...won't help with hearing nor cure T. So the clinical trial we have now is amazing. But it could still fail so we don't want to be too optimistic but there is more hope than before....way more.

 

I was reading about stem cells and hearing loss cure and basically its a lot harder than everyone thought. I think thats why everyone is going the gene therapy route right now.

 

The stem cell approach is a bit of a challenge since the only type of cells that could be used to regenerate new cilia are of embryonic origin.

 

I think that was only one of the challenges. I remember reading that the liquid in the cochlea would kill the cells if they were transplanted there.

 

It's not exactly that. Just injecting stem cells in the cochlea won't do anything. The cells have to be instructed in which type of cells to differentiate. The won't magically become hair cells just because they happen to be next to other hair cells. Gene expression must be regulated in order to sucessfully turn them into hair cells. If they don't become anything else, then yeah they're just going to wane off and die.

 

http://www.reuters.com/article/2015/05/26/us-science-embryos-obama-idUSKBN0OB1TF20150526

On the other hand, seems the ethicists in the US are hell-bent on stopping gene therapy because we might make some "mutants" down the line. It starts because of genetically altering embryos but moves to all genetic engineering. The media and public will outcry we are "tampering with nature and trying to be God" and research stops on anything called "genes". So like my rants in other posts, we may need other countries to step up and do this research.

 

supporting cell are not doing anything at the moment, they just sit there waiting to be used, so i doubt they do anything wrong in regards to hearing or T.

 

Supporting cells are definitely not useless :

http://www.nih.gov/news/health/jul2013/nidcd-25.htm

It doesn't make any sense that supporting cells are just sitting there waiting to be used, where the biological pathways to do so are naturally inactivated after birth, in mice at least. I guess we'll never know with humans as no one would want to induce hearing loss in their child while still in the womb.

You also have to think, what happens if this gene therapy is administered to people with relatively good hearing function. Supporting cells will sprout out and may destroy any hair cells that is already there. It's not specific in the sense that it selectively targets damaged areas of the cochlea to regenerate.

This therapy, in its current form, will only be viable to the profoundly deaf.

 

In my opinion, gene therapy and stem cells could both prove to be useful for treating or even curing tinnitus in the future - Theoretically they have the potential, but we've just gotta wait for results. I have some ideas of experiments i'd do if I had a lab + funding and i'm assuming that some of the researchers out there working on this stuff would have had similar ideas on ways of treating tinnitus with these technologies.

In terms of the first link you posted, I think it's just an information page showing the limitations - so shouldn't be taken in isolation.

Some pros and cons of gene therapy. 'Might' since we don't know yet.

Pros
- Might prove to be a solid way of treating hearing loss/tinnitus
- Might restore natural hearing
- Has shown therapuetic efficacy (in treating things other than hearing loss/tinnitus) previously

Cons
- Random genome integration site means it could cause tumors (unlikely)
- Immune responses against the viral DNA could cause damage (unlikely)
- Price / Ethics / Regulation

 

They've been able to differentiate stem cells into auditory nerves too!
http://www.natureworldnews.com/articles/7699/20140621/stem-cells-restore-hearing-study.htm