diagnostics – Nystagmus Network

Your nystagmus research questions answered – question 7

We asked a group of Nystagmus Network supporters what questions they would most like to put to nystagmus researchers. Then we found researchers to answer them.

Your questions were answered by Jay Self (JS), a Consultant Paediatric Ophthalmologist at University of Southampton and nystagmus researcher and Helena Lee (HL), a Consultant Ophthalmologist at University of Southampton and a nystagmus researcher.

Question 7: Can you tell us about gene studies and personalised medicine and how that might be a breakthrough for nystagmus?

(JS) The main development in genetics is being able to do loads of sequencing. That means finding out all the genes that lots of individuals have, what their particular spelling changes are and how they’re different to everybody else. That’s part of the 100,000 genome project.

The problem we have is then interpreting all that material. All of us will have a few million variants that are different from each other, that we shouldn’t really have or that we haven’t seen before. When you test 3.2 billion things you find all of this data and the question is that we haven’t all got a million diseases so some of them are causing things, some aren’t. It’s all about interpretation. This is where diagnostics comes in. We are getting better at that. It will lead to being able to group patients better. So when you then go on to test things or see what happens during life, or to see whether having funny toe nails really is related to nystagmus, you can start to look at groups and what these conditions are and then what you can do about them.

The second thing about gene therapy and gene changing, that absolutely is relevant. There are quite a few retinal conditions which cause nystagmus for which gene therapy is already going through. There’s one which is now NIHCE approved. This is going to be available through the NHS as one of the first ever gene therapies. It’s for a type of RP called Leber’s.

Gene therapy is a potential, but it goes a bit further than that. There are various drugs now which we know can change certain spelling mistakes. There are also some albinism changes that we’ve looked at before.

There are lots of other potential medical therapies which might change genetic outcomes. This is where this all might contribute, but we need to keep refining and refining the patient groups stage. There is no way any of that is going to work as a panacea.

It’s one thing to look at nystagmus as an end point. All this is about looking at the opposite end, at very specific changes.

Quite often, if you’ve got a single gene that causes a disease, some drugs might only work if it’s a particular type of spelling mistake in a particular part of that gene, if you happen to be male, etc. So you can end up with tiny numbers. One of the challenges is that originally gene therapy was reported as being able to correct spelling mistakes. But if you have 4,000 spelling mistakes you can’t develop 4,000 different gene therapies. So the idea now is to develop gene therapies that replace bigger chunks to treat more variations or more patients.

(HL) As we understand how the disease is developing as a result of each of the spelling mistakes, we’ll also understand how to target the treatment. It might not necessarily be gene therapy. It might be something as simple as a dietary supplement. We need the genetic test then we can say you can benefit from this combination of things. You need this and this to start with. We know this is how your disease will turn out, we know that this type of gene therapy would probably be pointless for you. The idea with personalised medicine is that each person goes in and comes out with a different set of advice and guidance or treatment.

The Nystagmus Network is enormously grateful to Jay and Helena who gave up their time on a sunny Saturday afternoon to answer questions from the nystagmus community so openly and fully.

Your nystagmus research questions answered – question 5

We asked a group of Nystagmus Network supporters what questions they would most like to put to nystagmus researchers. Then we found researchers to answer them.

Question 5: What are nystagmus researchers currently focused on?

(JS) There are lots of different avenues. There is an element of ‘If you’ve only got a hammer, every problem looks like a nail’. What I mean by that is that I’ve got a background in genetics, so I will look at all the ways genetics can help with nystagmus. We both have a background in clinical trials, so we always look at ways we can test things. If you’re an eye movement person who’s done 30 years of eye movement research you’re always going to look for an eye movement avenue. There are different people with very different expertise. We really need to broaden the net, because there will be people whose research is based on a particular molecule and they’ll try and work out how that is relevant to nystagmus. The more people you have and the broader it is, what tends to happen is that things start to come together and you get collaborations. Or there’s a totally different avenue of science that none of us even knows about.

The work that the Nystagmus Network are doing to try and broaden it out with broad calls for research is a brilliant idea. You never know. You could get people coming in from a totally different angle which might seem crazy or we’ve just never heard of that technology and suddenly that’s the thing that unpicks one part of it.

There are lots of people doing lots of different things, but you can always get more. There are themes to the answer. Lots of people are looking at diagnostics. People like me from the genetics point of view. There are quite a few looking at the use of eye trackers to help with diagnostics. There are others focusing more on support and wellbeing. Then there’s the treatment group as well.

There are also people looking at other conditions, such as retinal dystrophy researchers. Nystagmus is a major part of their phenotype, but, if you asked the patients, they wouldn’t tell you they’ve got nystagmus, they’d say they’ve got RP or cone dystrophy, or whatever. The nystagmus is just considered part of it from their point of view.

When we go to American Nystagmus Network meetings everyone is joined together by their common nystagmus and actually nobody thinks beyond that or questions why their sight is particularly bad or another person’s really good. It’s because they’ve all got completely different conditions.

There are 3 different groups of patients with nystagmus. There are those with neurological problems of which there is a huge long list, not just the acquired nystagmus cases but also children born with various neurological conditions. Then there are the ones with significant eye problems. For example, anybody born with very poor vision will get nystagmus. Then there is the group where it’s a bit more mixed, where nystagmus is a part of it. In that group I include people with idiopathic nystagmus, subtle aniridic changes or albinism.

Research is still going on into the neurological causes. Neurologists would, however, probably be about 5 sentences in before they mentioned nystagmus, because it’s not considered the main part of the phenotype.

The Nystagmus Network is enormously grateful to Jay and Helena who gave up their time on a sunny Saturday afternoon to answer questions from the nystagmus community so openly and fully.

30 years of nystagmus research – what a difference it has made

When my daughter was 6 weeks old a paediatrician at baby clinic told me she was blind. Just like that. No preamble. It was a devastating experience, a cruel message, bluntly delivered.

I went to see my GP, whom I knew well and trusted. She confirmed what I already suspected. My daughter wasn’t blind, but she did have something wrong with her eyes.

My doctor wrote the word nystagmus on a compliment slip and handed it to me. She couldn’t tell me any more. I had so many questions, but she had no answers for me. She made me an emergency appointment (another scary thing to hear at this point) with the ophthalmic hospital. It took two weeks to come through.

There followed a barrage of tests, each more alarming than the last, and at the end of it all we still had nothing but that ugly word, nystagmus.

I keep that compliment slip to this day as a reminder of how far we have all come. It’s what spurs me on to support other parents and raise awareness and understanding of this complex condition.

Since the early 1990s the Nystagmus Network has campaigned for and invested in nystagmus research whenever funding permitted. Thanks to the generosity of our supporters, there has been a substantial sum invested nearly every single year.

In the past 30 years clinicians have gained so much knowledge about this truly Cinderella condition: how to diagnose it, which of the many possible causes may be responsible for it and even how well a child will be able to see. They have also learned a lot about delivering worrying news to a parent.

Today researchers stand poised to unlock genetic secrets, manipulate enzymes and stop nystagmus in its tracks.

We have come this far together in just 30 years, a period which has seen the birth of the internet, the end of apartheid in S Africa, the fall of the Berlin Wall, the credit crunch, a decade of austerity, Brexit and, today, a global pandemic.

Who knows what is to come next for our brave new world? One thing is for sure. The Nystagmus Network will still be here, making your voice heard, working alongside the best brains in the country to find effective treatments and yes, eventually, a cure.

With your help, we can do this.

To donate now to the Nystagmus Network research fund, please click here.

THANK YOU.

Sue visits Queen’s Medical Centre, Nottingham

Dr Kong Yien Chin, a clinical scientist working in the Evoked Potentials Clinic at Nottingham’s Queen’s Medical Centre, invited the Nystagmus Network’s Sue Ricketts to view the clinic, meet the team and discuss potential collaboration opportunities on nystagmus research projects.

Sue was very impressed by what she saw. The last time she had stepped inside such a clinic was some 25 years previously, when her baby daughter had undergone VER (visual evoked response) and ERG (electro-retinogram) testing to confirm her diagnosis of congenital idiopathic nystagmus.

Although the appearance of the test materials themselves may not have changed much over the years (Sue well remembers gazing at a flashing checkerboard image as she cradled her daughter), Head of Evoked Potentials, Professor Christopher Degg, explained that new techniques have been developed and refined over the years to increase the depth and precision of the analysis of the readings, providing different information about visual function relevant to patients, including those with nystagmus. The technology involved is firmly at the cutting edge of medical science.

Sue came away with an appreciation of how it can be beneficial for people affected by nystagmus to seek appropriate assessments for best possible understanding of their condition.

Dr Chin commented:”This meeting is an important milestone for the Nystagmus Network and the Evoked Potentials Service in Nottingham. We have the desire to play a significant role in future collaboration with the Nystagmus Network and alongside current and future research groups on potentially life-changing research that will particularly benefit those affected by nystagmus.”