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research focus research focus The clinical trials for MonoPepT1De are open to anyone aged between 18 and 40 in the 100 days since being diagnosed with type 1 Vaccine trial shows early promise Mark Peak man with his lab group Our volunteer writer Nikhil Patel finds out the latest on the research at King’s College London which is testing a vaccine with the potential to at least slow down beta cell destruction Know your facts on autoimmunity 14 A type 1 diabetes vaccine, with the potential to be ‘absolutely brilliant’ according to a patient who has taken part in its trial, is becoming a real possibility. In fact two clinical trials at King’s College London are seeking to develop a vaccine that could slow or halt the process that destroys insulin-making cells. These innovative trials are being pioneered by Professor Mark Peakman who, during his many years of type 1 autoimmunity research, hit upon the idea that it was possible to reverse the damaging immune system response by creating a ‘protective’ immune response. His collaboration with other experts, particularly Professor Colin Dayan of Cardiff University, turned this initial hypothesis into two trials, MonoPepT1De and MultiPepT1De, that will assess whether a recently diagnosed person’s ability to make insulin can be preserved. Thanks to JDRF supporters, the charity has been able to fund these trials, which use tiny fragments of a precursor to insulin, known as ‘proinsulin’, to teach the immune system to allow insulin-producing cells to flourish. This is very similar in concept to recent work on treating allergy that uses peanut extracts to teach the body to tolerate peanuts. The clinical trials are open to anyone aged between 18 and 40 who have been recently diagnosed with type 1. Taking part involves receiving small injections and being monitored regularly over a 6-12 month period. Alex Collins, 34, is an investor from London who recently took part in Autoimmune conditions affect around four million people in the UK. the MonoPepT1De trial. He was diagnosed in August 2013 and signed up to take part in the trial a couple of months later. He said: ‘It’s impossible to say whether my condition has improved directly because of the vaccine, but since I got my blood glucose under control after diagnosis my HbA1c has been between 5.7 and 5.9. ‘In other words my levels are very good, which may be partly because of the trial.’ ‘[The vaccine] would be absolutely brilliant for anyone newly diagnosed. If doctors can halt or even slow down the progress of type 1 once it’s been diagnosed it would have a huge impact on the quality of life of those suffering from the condition.’ Alex, a dedicated JDRF supporter who has run the London Marathon to raise funds for research, added: ‘I cannot recommend the clinical trial highly enough. ‘Having a lot of contact with diabetes professionals is fantastic. I’m impressed with the care I get from the NHS and I get on well with my doctor, although I only see him for half an hour every six months. Particularly when you’re newly diagnosed it is amazing to spend more time with diabetes professionals – for that reason alone it is worth doing.’ h a nn t a n o J de rso He n Volunteer Editor-in-Chief When protection is the best means of attack Mark Peakman, Professor of Clinical Immunology at King’s College London, talks to Jonathan Henderson, editor-in-chief of Type 1 Discovery, about the MonoPepT1De and MultiPepT1De trials. This is the latest step in pioneering research into developing a vaccine J onathan Henderson: You say you are taking ‘a vaccine-type approach’ to slowing or preventing the type 1 process. What does this mean? Mark Peakman: The concept of a vaccine is that you stimulate the immune system in a safe encounter that protects the host from whatever the threat is. Usually you’re doing this against a virus and so you present the immune system with bits from the virus in a harmless way. The aim then is to develop a response that protects against an encounter with that virus in the future. In type 1 diabetes we believe that the immune system identifies the insulinproducing parts of the body as a threat. So we’re aiming to present these elements to the immune system in a safe way that promotes a protective response rather than an aggressive one. JH: And this is what these trials are investigating? How do MonoPepT1De and MultiPepT1De differ? MP: MonoPepT1De was a prototype that allowed us to get into human trials, show safety and test biomarkers and tolerability. MultiPepT1De is the second generation that will be ready to go into trials for the first time in 2015. MonoPepT1De was a single fragment from the beta cell that we were using as a drug and MultiPepT1De is multiple fragments from the beta cell. So we believe it should have greater breadth and be more powerful. Many people with type 1 live with at least one other autoimmune disorder. Around eight per cent have coeliac disease too. 15 research focus research focus There’s another dimension to JDRF, which is that they bring you into the right room. When we’ve needed to speak to other people or institutions, JDRF has been incredibly helpful Your support has helped us to make this research possible. To fund more research like this, visit jdrf.org.uk/donate JH: A few years ago we interviewed you about a JDRFfunded study you were running called DGAP (Diabetes Genes, Autoimmunity and Prevention Project). Does this fit with the work you’re currently doing? ts Helper T cells responding to isle Some cells have a good response (green), others a bad one (red). The cells that produce both responses (yellow) are particularly interesting to Prof Peakman’s team. The concept of a vaccine is that you stimulate the immune system in a safe encounter that protects the host from whatever the threat is Know your facts on autoimmunity 16 JH: These trials are focusing on adults newly diagnosed with type 1 diabetes. Does this work have any relevance for people who have had type 1 for many years or for children? MP: First, it is worth saying that there is some research just coming out that suggests for the first time that there might be benefits for people who have had type 1 diabetes for much longer than three months – even up to a few years. But in answer to your question, yes, we are hoping to launch studies in younger patients with type 1 and some small pilot studies in individuals who don’t have diabetes yet but who we know are at risk. This is definitely on our radar at the moment. JH: If treatments such as MultiPepT1De can work to prevent type 1, how would you get it to the right people at the right time? MP: What all the animal studies have suggested is that the earlier you can get this kind of treatment to patients the better. So if the trials show promise we’re probably talking about robust screening programs of high-risk individuals. These might be individuals who have a family history, but one might even consider screening the school-age population. And this is not such a ridiculous suggestion as it may sound. It is a model that is actually being developed in Bavaria, Germany, at the moment. So this is how we might get to the high-risk groups as early as possible. There are thought to be more than 80 autoimmune conditions, each affecting a different part of the body. MP: Yes, because we showed in DGAP that there are probably different types of immune responses in patients with type 1. These different types of responses may require different kinds of therapeutic approach, which we’re beginning to call personalised medicine: the right drug for the right patient at the right time. Based on the work we did in DGAP we think that the vaccines may be even more effective in some people than in others. JH: Has JDRF played a significant role in your type 1 research? MP: Yes it has in many different ways. For example, JDRF funded the basic DGAP studies and the MonoPepT1De clinical study. But there’s another dimension to JDRF that people are probably less aware of, which is that they bring you into the right room. They get you talking to the right people. This has been very important in taking our development forward. When we’ve needed to speak to other people or institutions, whether it be other funders, pharmaceutical companies or regulators, JDRF has been incredibly helpful. JH: Other than funds, what would help speed the progress of your research? MP: Being able to get trials up and running and enrolled quickly. It is one of the things that keeps me awake at night: are we going to be able to deliver the number of patients we need, in the time when we have the funding? Because when you’ve got a study open and you’re not recruiting you’re basically burning cash. So getting patients enrolled and engaged and getting them to stay in the studies is tremendously important. Biography Mark Peakman trained in medicine at University College London and pursued postgraduate training in clinical immunology. After he received his PhD based on studies of the immune system in type 1 diabetes, he held senior positions at the University of Pittsburgh before returning to the UK, and he now oversees a research group at King’s College London in the Department of Immunobiology. If you’d like to get involved in a clinical trial, which is a vital step in making this vaccine a reality, visit jdrf.org.uk/trials. You can take part if you’re aged between 18 and 40 years and have recently been diagnosed with type 1 diabetes. Many autoimmune conditions share similar underlying mechanisms – this means that drugs developed to treat one condition, such as psoriasis, may be effective in other conditions, such as rheumatoid arthritis. 17