Gene therapy to treat glaucoma

In countries like the UK, about 2% of people over 40 have the eye condition called glaucoma. This is where pressure builds up inside the eye, damaging the optic nerve. Untreated, it causes irreversible blindness and is a major problem worldwide. Now, researchers have come up with a way to use gene therapy to stimulate the damaged optic nerves to regenerate in experimental animals with the condition. Veselina Petrova worked on the study at Cambridge University, and spoke about the work, published in Nature Communications, with Adam Murphy...

Veselina - In our study, we looked at the ability of a molecule called protrudin to promote regeneration and repair of the injured nerves, and we've used three different models to test this. In one model we grew nerve cells in a dish and injured them using a laser, and in two other animal models we actually use the optic nerve damage to look at the efficacy of protrudin. The optic nerve is actually the nerve that connects the eye to the brain and which relays visual information. And what we found in our study is that in all three models, delivering protrudin to the nerve cells actually improves not only their survival, but also their repair and regrowth after injury.

Adam -
Could you tell us what protrudin is then?

Veselina - Yeah, protrudin is a protein which is normally found in the cells. And what it actually does is it acts as an adaptive protein, and it brings together a lot of things that are important for growth, and concentrates them exactly at the area that they're needed at during growth after injury.

Adam - And then when this chemical is in cells in the eye, it means it regenerates them and makes them live longer. Is that right?

Veselina - Yes, that's right.

Adam - And then how do you know that it works? Mice are hardly famous for their eyesight...

Veselina - Yeah, that's true. We are currently doing further studies to actually look at the functional output to see whether they can regain some of their vision back. But this is some of the greatest regenerative effect that we've seen with any treatment in our lab. We believe that such a massive outgrowth... if we can make these nerves grow back so there are target areas in the brains, then that could really help functionality. But we're currently studying this.

Adam - Do you know if this is a long term effect, or is it just temporary?

Veselina - So we've only looked in our mouse models for several weeks after injury, and we could see really sustained effect in humans. Of course we have to test this, but there's currently some treatments that have been licensed specifically for the eye. And they really show that if you deliver gene therapy to the eye, that leads to a long lasting effect. So we hope to see a similar thing with our gene therapy approach.

Adam - And how likely is something like this to work in humans?

Veselina - There's already treatments that are available in the UK that include gene therapy in the eye, and there's several others that are underway in clinical trials. So gene therapy does work in the eye. How likely our treatment is to work in the eye? As I mentioned, we've only tested this in animals, so there is a lot of further work needed to see whether first of all, it's safe; also effective in humans. But we're really hopeful that even if it isn't, we've discovered a new pathway involved in the process of regeneration, which could potentially provide some targets for pharmaceutical treatment.

Adam - What about other conditions where there's nerve damage like spinal cord injury? Could a similar kind of approach work there?

Veselina - We tested this in the eye, but the eye is part of the central nervous system, and the optic nerve is part of the central nervous system, and nerves of the spinal cord and the brain are also part of the central nervous system. So we believe that similar processes are happening in all these systems, and possibly we could apply what we found in the eye to the spinal cord and the brain. And we're actually doing these studies in our laboratory right now. So hopefully I'll have an answer for you later on.

Adam - How do you actually get this protruding into the eye?

Veselina - We use viruses which have been inactivated, so they're not infectious. We just take the outer coat of the virus and package the gene inside, and then we trick the cells of the brain into thinking that the virus is infectious, so they take up the virus and the DNA is released and integrates into the eye cells' DNA. So it's kind of like a Trojan horse, If you think about it: we just trick the brain to think that the virus is infectious, but it's not actually, we just use it as an approach to deliver the gene to where we need it.