As a taste of what to expect at our Festival this year, we thought we’d showcase some of our best and brightest speakers and the fascinating topics they’ll be speaking on. Stay tuned for even more.

Front Line Genomics was created with a social mission after our founder lost his father to mesothelioma, a rare form of cancer commonly caused by exposure to asbestos. That’s why we thought it so important to showcase Nick Sireau, a man who has done incredible things to further science and healthcare after a rare disease, Alkaptonuria or AKU for short, hugely affected his life. Nick co-founded the AKU Society to combat the disease, and is now about to finish a seven-year study into a drug which play a major part in eradicating AKU altogether. 

What Does the AKU Society Do? How was it First Founded?

I’m the chairman and the CEO at the AKU Society, which is a patient group working on an ultra-rare disease called AKU, otherwise known as “black bone disease”. We have an office and a small team of four based in Cambridge, though most of our research happens in Liverpool at the Royal Liverpool University Hospital.

The AKU Society was founded in 2003 by a doctor called Dr Ranganath and his patient Robert Gregory, both in Liverpool. I joined shortly afterwards and we set it up as a charity. At the beginning we set up a website, contacting patients and giving them updates on AKU news, making contact with researchers and trying to get it started. The society grew from there.

How Difficult Was it to Co-Found Your Own Company? What Tips Do You Have for Others Starting that Journey?

First, see if there’s an existing patient group. If so, join forces with them. If not – or if they’re not doing a very good job – set up your own patient group. For that you need to register as a charity with the Charity Commission, set yourself up as an organisation and get a board of trustees, and then start making contact with scientists and researchers to push research forwards.

Another crucial piece of advice is to keep going and be persistent. It’s important to never give up, because the early years of setting up a patient group or charity will always involve very hard work. It takes time to build credibility, to get traction, and to get people interested, but it does work.

Additionally, if you’re a patient group it’s good to look at the existing science surrounding a particular disease you’re working on. We found for example that even though AKU was first identified in 1901, one hundred years later there was still very little research on it at all. What we did then was look at the research that had been done, and built on it. For this we raised funds to perform an autopsy of a patient to find out more about the disease and how it had affected them. We raised funds to do an animal model of the disease, and that gave good indications of what might actually happen. By doing those we got very strong scientific credibility.

What Were the Toughest Challenges You Faced in Starting This Organisation?

There were three main problems: the first was a lack of patients. We vaguely knew that AKU was about one in half a million, or four in a million or so, but we only knew of four patients and two of them were my children! So we did a massive patient identification campaign where we contacted all 50,000 GPs in the UK and sent them material – one was just a piece of paper with photos of the four diagnostic criteria of AKU, those being black urine, black spots in the eyes, black ears and black bones. We also sent a questionnaire to see how much they knew about it and to see whether they had any patients – and that allowed us to recruit around 60 to 65 patients, which was a good start.

The second challenge was finance. The charity sector is very competitive, and there are lots of applications to funders and we found it difficult at first to raise the funds. We brought in a fundraising consultant who did a short strategy for us and who later told us he didn’t think we had a single chance of raising the money! Luckily he didn’t say that at the time, so we went ahead. In the end we were very successful, but it just took time.

The third challenge is that of the science. Science takes time and you can’t rush it, and it depends a lot on financing. So until you have the financing in place it’s hard to do the science that you need.

How has the Rare Diseases Sector Changed Since the AKU Society was First Set Up?

The area of rare diseases is much better now than it was 15 years ago, and there are a number of reasons for that. It has become a lot more organised: now, there are a number of individual patient groups out there but there are also a number of umbrella groups working as a unit for the benefit of the sector. In the UK there are the Genetic Alliance UK and Rare Disease UK, and in Europe we have the European Organisation of Rare Disorders (EURORDIS). They have all campaigned at policy level to make sure there are national rare disease strategies, but they have also fought battles at EU level to make sure there’s funding available for large research projects, so the sector has definitely changed a lot.

I think the science has also changed very fast. Fifteen years ago people thought that gene therapy was far in the future, and now in 2018 we’re starting to see some gene therapies actually entering the clinic, which is really phenomenal. Our understanding of the science is also much better, as is our understanding of the genome and the factors involved in these rare genetic diseases, so I think it’s changed a lot.

How do You Foresee Brexit Affecting the Rare Disease Sector?

Brexit is not good for rare diseases. That’s because the only institution which can really think on a broad-enough and long-term enough level for rare diseases is the EU, as that organisation can think in seven or eight year timeframes, which national governments can’t due to re-election every four or five years.

Also, what’s “rare” in one country can actually be almost common at the EU scale. The European Commission has been funding a lot of rare disease clinical trials, up to around six million euros per trial. This is a lot more than you’d get in any national country, and separating ourselves from the EU would mean we wouldn’t see that funding level again. So no, Brexit is not good for rare diseases in the UK or in Europe.

By the End of January 2019, You’ll Finish a Seven-Year Study of a Drug to Combat AKU, Known as Nitisinone. How Will the AKU Society Develop After this Project is Complete?

Even after the project is finished, there’s still a lot of work to do. We’ll have six months to look at the data, followed by six months to prepare an application to the European Medicines Agency, which then has a year to look at the information. If in about two years’ time they approve Nitisinone and give it a licence, it has to go through the national funding bodies such as NICE in the UK. That means there’s still a lot of work to be done.

Beyond this, we’re also looking at other therapies. We’re currently exploring the possibility of a co-therapy that can reduce the side effects of Nitisinone, we’re looking at gene therapies, and we’re looking at repurposed drugs, so there’s definitely still a lot to do.

What Other Projects Are You Running in Addition to the AKU Society?

I set up a charity called Findacure about five or six years ago because I was being frequently contacted by parents of children with rare diseases who wanted to set up patient groups and were asking how we did it – that is, how we set them up, how we raised the funds, how we interacted with industry and how we set up clinical trials. Because of this I set up Findacure, which helps to grow patient groups and enables them to better build their capacity.

One of the things Findacure does, as an example, is to conduct annual peer mentoring programmes where we connect emergent patient groups with more established ones, or maybe with a PR agency if they’re interested in doing communications, and then over the course of the year ensure they’re mentored and trained in specific areas where they feel they need to develop. We do several workshops throughout the year on different issues such as fundraising, clinical trials, patient identification. We also work on drug repurposing, which is the idea of taking existing drugs and re-using them for other conditions, because existing drugs which have already been approved obviously don’t have to go through all the toxicology screenings and that sort of thing. Since a lot of the time drugs can be used for several conditions, we can find solutions to diseases without having to start from scratch every time.

You’re Speaking at the Festival of Genomics 2019 on AKU and Your Time Spent Combating it. Do You Think Talking About and Disseminating This Information at Festivals Helps Forward Your Cause?

Absolutely. A lot of what we need to do is to raise awareness about these issues. A lot of people aren’t aware that there are about 7,000 rare diseases in the world affecting millions of people. That’s why we have to go to these festivals and communicate it.

There’s also the fact that the study of rare diseases helps us understand common diseases: for example, the study of AKU has helped us understand a much more common disease called osteoarthritis, for which there is no treatment. But we also know that the study for instance of an ultra rare disease called familial hypercholesterolemia led to the development of statins, which are widely used to lower cholesterol and prevent heart disease. So there’s a very strong interest in making people understand why we need to study these diseases. 

Nicolas Sireau will be giving a talk on “Developing a Cure for AKU (Black Bone Disease) – A Personal Story” at 1pm on the 23rd of January, in theatre 3.