I welcome Mr. Joe Mooney, director; Ms Karen Pickering, information officer; Mr. Hubert McCormack, administrator; Ms Kate Power, respite co-ordinator; Mr. Jimmy Mooney; and Dr. Matthew J. A. Wood, member of UK MDEX Consortium. I invite them to commence their presentation on research advances. We do not want to restrict the group too much, but we can only allow 40 minutes for the presentation because we are meeting another group afterwards and must also proceed to the Dáil for votes.
Muscular Dystrophy Ireland: Presentation.
I thank the joint committee for its invitation to come and explain muscular dystrophy, what Muscular Dystrophy Ireland does and the research project for which we are seeking funding. I will hand over to Ms Kate Power who will explain muscular dystrophy and the service we provide.
Ms Kate Power
Muscular dystrophy is a collective term for a number of neuromuscular conditions which are characterised by progressive degeneration and weakening of the muscles and which affect both children and adults. Ms Pickering will go into more detail on Duchenne muscular dystrophy, while I will outline the services provided by and the role of Muscular Dystrophy Ireland.
Our main aim is to provide information and support for our members through various services, including respite services. We provide assistance for families and members in accessing in-home respite care, holiday respite care, camps and weekend breaks. Our youth service focuses on the personal and social development of our young members. Youth workers draw up a programme of activities based on home visits, youth clubs, social outings, summer camps and workshops.
We employ some personal assistants who work with members and promote independent living. We have family support workers in each Health Service Executive region who link directly with families and provide information, advice and support on the different stages of muscular dystrophy. We also link up with other health professionals and service providers in this regard.
Muscular Dystrophy Ireland co-ordinates two clinics, one in the Central Remedial Clinic with Dr. Brian Lynch for children and the other in Beaumont Hospital with Dr. Orla Hardiman for adults. We are in the process of establishing a third at Our Lady's Hospital for Sick Children, Crumlin, to monitor the cardiac function of our young members. We have an information service and an information officer in Dublin who provides information for our members, the public and other health professionals. We also produce a newsletter which provides up-to-date information on medication, treatment and national and international events and activities within the organisation. Linked to this we also have a website which provides information.
Transport is a major issue for many of our members. We have a transport service and retain a driver in Dublin and Cork. We offer a number of accessible buses or vans to enable members to attend hospital appointments and access employment, education and social and recreational activities.
Muscular Dystrophy Ireland is committed to supporting and funding research into neuromuscular conditions aimed at improving quality of life and developing a treatment or cure. I will now hand over to Ms Pickering who will provide information on Duchenne muscular dystrophy.
Ms Karen Pickering
I will give an overview of Duchenne muscular dystrophy and explain why research is so important.
Duchenne muscular dystrophy is the most common type of muscular dystrophy and a serious condition that affects approximately one in every 3,500 male births. Symptoms in boys affected by the condition normally appear around the ages of three to five years and those with the condition normally need to use a wheelchair between the ages of eight and 11 years. The upper body of those with the condition loses strength and they need assistance with personal care and manual tasks. The muscles used for breathing and the heart may also be affected and these problems considerably reduce the lifespan of boys affected.
Current treatment research focuses on Duchenne muscular dystrophy because it is the most common type of muscular dystrophy and affects people so severely. A treatment that would affect the progression of the condition would make an enormous difference to a boy's life. Currently, there is no cure for any type of muscular dystrophy, but it can be managed to some extent. This requires a co-ordinated approach, the reason multidisciplinary neurology clinics are so important.
Physiotherapy, heart and respiratory checks and occupational therapy services are essential requirements. Ms Power has mentioned access to respite care and personal assistant services, which are necessary to provide boys with the ability to live an independent life. The services are over-subscribed and Muscular Dystrophy Ireland always fights for additional funding for them.
To illustrate the importance of managing the condition, a study of the statistics of the Newcastle muscle centre in the north of England shows that the average lifespan of a boy with Duchenne muscular dystrophy increased from 14.4 years in the 1960s to an average of 25 years in the 1990s for boys who had been ventilated. This is a significant development, but 25 years is not long enough for the boys concerned and their families. For this reason, there is a real need for research to find new therapies.
As Ms Power said, Muscular Dystrophy Ireland aims to support and fund research into muscular dystrophy. However, it is a small organisation and only has a small research fund. For funds we depend on the fundraising efforts of our members. Because of this we tend to focus on support services before funding small-scale research projects. However, there is so much optimism about the exon skipping research in the United Kingdom that it has led to a number of parents of children with Duchenne muscular dystrophy fundraising to support it. This research has captured people's imagination, but ultimately the amounts parents can raise are small in relation to the overall cost of the research. We believe it is important for Ireland to support the research to ensure it is funded to a conclusion that will, I hope, result in a treatment. Also, support will ensure that when a treatment becomes available, families in Ireland will be able to access it as quickly as possible.
I will hand over now to Dr. Matthew Wood from the University of Oxford who will explain more about the research.
Dr. Matthew Wood
I thank the joint committee for the opportunity to address it. I will begin by referring to page 2 of the presentation document. Duchenne muscular dystrophy is a very severe but very common disorder. It results from errors in the gene called dystrophen. This gene is very important for muscle function and errors in it result in the lack of dystrophen protein, the reason muscles degenerate over the course of ten to 20 years.
One of the advantages of research conducted into Duchenne muscular dystrophy is that it has benefited significant areas of modern medicine. The dystrophen gene was the first gene to be cloned, which helped pave the way for the genome project and genetic diagnoses in common use.
In the 1990s we worked out the function of this gene. This has led the way to work out the functions of many other genes and is now paving the way for gene therapy in the 21st century. The research has really led the way in many areas of medicine.
There is no cure for this disease at present so that is the reason this research is so important. In order not to put all one's eggs in one basket, people are investigating many different types of putative therapies. These include gene therapies, stem cell therapies and several other types of therapy.
What we have been working on is a very promising type of gene therapy that we call exon skipping. The aim is not to put a new gene in to replace the dystrophen that is lost but to try and repair the existing gene. The way we do this is to try to engineer a little chemical drug that can skip over the errors in the gene so that when the genetic code is read, the mutations or the errors are skipped over and there is still a proper reading of the gene. We design very short pieces of DNA, the genetic material, and these are able to attach themselves to the dystrophen gene in order to obscure the errors so that when the code is read, these errors are missed out. It was a very exciting idea a few years ago and we have been able to put that into practice and test it out in a number of pre-clinical studies where we can test these out in very good animal models which mimic the human disease. The first reports in 2003 were a series of studies where we were able to show that this type of treatment could repair the gene and result in the production of some of the dystrophen protein in muscle. Because the protein is so critical, this was able to restore some degree of muscle function. We were able to increase the production of this protein and restore the function of muscles. This was done in animals, in mice.
As a result, in 2004 we formed a consortium in the UK called the MDEX Consortium. This was designed to bring together researchers from a number of institutions to take this forward into clinical development and trials so that we could really evaluate its potential.
I have shown the committee an indication of how we are proceeding with these trials. We are gearing up for the very first phase one clinical trial which is due to begin in London and Newcastle towards the end of this year, 2006. The study will be in a very small number of patients — about nine. We will inject our chemicals that are able to do the exon skipping into one muscle in the foot. The study is principally designed to test the safety of this treatment. We will also get some information about whether it works in a human being because we have not tested that yet.
Thereafter we need to work towards a systemic type of treatment that will treat all muscles and so we can deliver the drug systemically by way of the bloodstream so that it could reach all muscles. This will be quite a bit more work and it will require a fair bit of research and preparation and future clinical trials where we test out delivery to all the muscles.
The consortium we formed has an advisory board that advises us on how we conduct our research. We work with a range of partner charities and funders. We have international collaborators and we are now working with industrial partners who will produce the drugs for us.
The first clinical trial was able to be planned and undertaken as a result of the genetics initiative, the genetics White Paper published in the UK in 2003. From the UK Department of Health we received £1.6 million worth of funding to develop the first phase one trial. More research is required to prepare for the systemic trial. We have received funding to do this from the muscular dystrophy campaign in the UK. The Muscular Dystrophy Association of Ireland has very generously committed to supporting this research with a sum of up to £100,000. There is still a shortfall of funding in this area.
Funding from the UK Medical Research Council is beginning to be in place for the next phase of the clinical trial but there is a significant shortfall in this area.
I refer to the slide that lists the members of our consortium with our principal collaborators from the University of Western Australia in Perth.
I hope our presentation will have given the committee a view of what MDA does and the research project that we are involved with in England. I thank the committee.
I thank the delegation for its presentation which is very valuable to the committee.
I wish the research well. It sounds like a very exciting project. Will these clinical trials be carried out on adults?
Dr. Wood
Not on adults. The treatment will ultimately need to treat very young boys. We would like to start with boys as young as possible but for ethical reasons we are unable to recruitboys younger than ten years old for the first trial. It will be boys between the ages of ten and 14 years.
I wish the project well. We are not as developed in Ireland with regard to the issue of having a genetics White Paper but it would be a very good idea if we did.
I note there is some support from Ireland. All politics is local and I wonder whether the delegation considered including any Irish researchers in this project? I would have thought it was the kind of project that might be useful on a cross-national basis. I note there is a person from Australia. Is it Dr. Wood's view that there are people here who would be of benefit to him?
Dr. Wood
Irish researchers are working in the field of muscular dystrophy, many of whom will be familiar with this work and some of them might well be very valuable contributors at later stages in the studies. This exon skipping work is highly specialised. I have recruited to my laboratory one of the two or three people in the world who can do what I need to do and she is from China. It is very specialised work. We look for the very best people wherever we can find them.
I have three brief questions about the recommendations in Dr. Wood's report. I note that the services are in Dublin and that this creates difficulties for people outside Dublin. Has Dr. Wood any proposal as to how that can be changed for the better? Are there certain locations where services should be provided since they cannot be provided everywhere? On the question of a multidisciplinary approach which is a theme that is raised by delegations to this committee, will the delegation expand on this approach? On the question of personal assistant, PA, services, will they indicate what the shortfall is? Is it a case of needing 25% more?
We are a national organisation and we have staff all over the country. We have a family support organisation. We employ eight family support workers between part-time and full-time workers. We also have a youth service. We are trying to expand services such as transport. We link in with other organisations. However, some people with the condition live in very remote areas. We do our best and we are a member-focused organisation. We try to meet the needs of the members as much as possible.
We promote the idea of multidisciplinary teams. Dr. Lynch in the Central Remedial Clinic has a multidisciplinary team which includes a dietitian and a physio. Mr. Jimmy Mooney is a parent of a boy who has attended the CRC and will be able to speak about the CRC and its facilities. The adult clinic in Beaumont does not have a similar multidisciplinary service. We have a neurologist, Dr. Orla Hardiman, and she refers patients. The idea would be a one-stop shop whereby a person could come from, for example, Donegal and go to Beaumont and do his or her own physiotherapy, respiratory and pulmonary functions — the whole works. Unfortunately, that is not happening. We have been lobbying to try to get a team in Beaumont that would cater for that, but it is not in place yet.
On the personal assistant, PA, service, it is like asking how long is a piece of string. As it is a progressive disorder, people with muscular dystrophy may only require 20 hours in 2006. However, by 2010 they may need 24-hour assistance because of the progression of the condition. We would have approximately 20 members on our books seeking additional PA hours. We do not publicise it because we do not want to break people's hearts or say that we will try to lobby. However, we provide emergency respite for people with muscular dystrophy. If they are badly stuck or a family member is sick, we have a number of trained people who can step in.
Again it comes down to funding. We have a limited budget of €1.2 million, as outlined at the back of our presentation. To do everything we would like to do would cost €1.6 million or €1.7 million, which indicates under-funding of €500,000. Unfortunately we must cut our cloth to suit what we can do. We apply for everything that is going, from the dormant accounts fund to the national lottery funding.
We focus everything on our members. Our members tell us what they want and we try to deliver. I will ask Mr. Jimmy Mooney to talk about the Central Remedial Clinic.
The Central Remedial Clinic, CRC, is very good. Dr. Lynch is an excellent neurologist and he has all the different places set up. There are other things he would need to make up his team. He is always focusing on his team. However, ultimately, he needs his tools for the treatment of these children. When we got the diagnosis for Liam two years ago — he has just started school now — there was no treatment for it. It was limited to steroids, which have their own problems. It may slow it down for a time. We were told that he might make it to ten years and would need to go in a wheelchair. We thought that was bad enough, but then we heard that his breathing would give up and his heart would have problems. Late teens or early 20s was the diagnosis we got. The doctors knew about it, but it was hard to get information.
I went to some of the conferences. At an MDI conference in Dublin, Dr. Ian Graham, a colleague of Dr. Wood's, first explained about exon skipping. While many different avenues exist, I felt that would be the only hope for our child. I went to other conferences and followed up the matter and it seemed to be the view of many of the parents. All the science backs it up. I went to America to a conference and I went to London twice. It is the general consensus that exon skipping is the most realistic option for the children.
Ms Power
I wish to add one point about the PA hours. It is important to realise that within MDI, carers become the main providers of PA. Duchenne muscular dystrophy starts at such a young age and families are the main carers for such a young child. PA hours are just not available. We battle with or link with the IWA, CIL and Health Service Executive, HSE. We can end up in an emergency situation where the parent becomes ill. Carers in families really need PA hours.
I thank the delegation for the information. It is encouraging that progress has been made. I would like to hear much more about exon skipping, including when it will happen. Any progressive disease can be frustrating and halting the progress is the main objective. I find it very frustrating that neurologists are so overworked. While recommendations have been made to increase their numbers, it does not appear to be happening. Perhaps Dr. Wood would outline his experience in accessing neurology services. He spoke about increasing life expectancy. What is the life expectancy now and how does Ireland compare internationally?
I did not hear Dr. Wood refer to stem cell research and I ask him to expand on any developments in that area. He mentioned the trials and that the earlier intervention takes place, the better. Starting to work with a child between the ages of three and five would be ideal to arrest progress. He mentioned that it is not possible to carry out trials involving children younger than ten. This gives rise to a conundrum which I would like the doctor to address.
Responsibility for giving the consent of a child below 18 lies with parents. While I do not know whether it happens here, we have seen the negative consequences of some drug trials recently. We also hear of people in other countries receiving payments for their involvement in trials. Perhaps Dr. Wood would outline how it is intended to break that barrier. It needs to be broken in some way. Dr. Wood spoke about trials in his university. Is there a worldwide link and are other countries working together to make progress or are individual groups trying to get there first?
It is frustrating to hear a group outline how it needs to apply for funding from various sources, including the national lottery. It makes it sound as if it is out with a begging bowl. The group should be funded by the Department of Health and Children and should not be required to seek funding elsewhere.
Obviously Dr. Wood should link with Science Foundation Ireland on research as it has teams of researchers. Having listened to the doctor's presentation, I believe there would be great potential in linking with the foundation to share ideas and work on projects. He mentioned a budget from the Irish end of approximately €100,000. Considerably more money should be available through Science Foundation Ireland by comparison with that paltry sum.
I compliment the delegation on the information presented today. We should support Dr. Wood's exon skipping project. Is there a delay in getting people to clinics for a diagnosis? It would seriously affect a child's development if he or she were having chest infections, etc., at the same time. No mention was made of genetic counselling. Is there adequate access to genetic counselling for families? I was very surprised to read that 50% of cases turn out to be spontaneous genetic mutations. Regarding personal assistant services, which are so important, I repeatedly get complaints that FÁS trainees are being used, when such services should be provided by people who have worked as personal assistants for a considerable time.
I would like to conclude by referring to a transport-related complaint that I often hear from people who use wheelchairs. Reduced rates apply to the licences of taxis which are supposed to be wheelchair-accessible. I understand that the drivers of such taxis are frequently reluctant to pick up, or even take bookings from, people who use wheelchairs. Has this been a problem for the representatives of MDI?
I will answer the question about clinics and neurological services. The clinic in Beaumont Hospital was established after MDI approached Dr. Orla Hardiman over two years ago. We wanted her to set up a clinic because many people in this country were not seeing a neurologist. There is a lack of neurologists in the country. We were concerned that people have to travel long distances — from Donegal or Cork, for example — to see Dr. Hardiman. As I said earlier, some people get to talk to Dr. Hardiman for just five or ten minutes, unfortunately. During that time, she cannot do much more than diagnose people, talk to them about their conditions and recommend other treatments to them. Some people have to spend four hours travelling home after seeing the doctor for just ten minutes. MDI is part of the Neurological Alliance of Ireland, which is campaigning for more neurological services. People can spend up to six months on the waiting list for such services. When we are contacted by people who wish to see a neurologist, we put them in direct contact with Dr. Hardiman. I commend Dr. Hardiman, who is very good and very accommodating. She agrees to see people in emergency circumstances, etc.
I would like to speak about the issue of age, as it relates to this discussion. In the respiratory area, we have seen an increase in the use of breathing aids, such as Breeze equipment and bi-PAPs, in Ireland. There seems to have been an increase in the average age, thankfully. It is still not enough, however. We have to try to grab people early. MDI is currently in negotiations with Dr. Richard Costello, who is a respiratory consultant in Beaumont Hospital. He wants to establish a monitoring service for people with this condition so that they do not have to travel to Dublin. The service is based on the wearing of a watch at night-time to measure people's heartbeats, carbon dioxide levels and oxygen levels, etc. Dr. Costello hopes to get a system up and running so that many people can be saved. It is also hoped to introduce the bi-PAP, which would increase the length of people's lives. I have seen for myself that the use of bi-PAP machine can increase life expectancy. Some members of MDI who have Duchenne muscular dystrophy are 28 years of age and are still going strong.
Things are improving, but we are very hopeful for this extra scheme. This is the most exciting and hopeful thing I have seen in the almost 30 years in which I have been involved in MDI. Parents are constantly ringing me to look for information. They want to know where they should go and what they should do. I have had people crying in front of me, asking me where they should go and telling me that the cost of going to America or Australia does not matter to them. I have to tell them that nothing is available at the moment, unfortunately. We are very hopeful for this because it is a big thing.
Quality of life is an important issue for MDI. The personal assistant service was mentioned in the context of the FÁS scheme. One can spend 19.5 hours a week on a community employment scheme, but one's disability does not go away after that time, unfortunately. We have to live with disability 24 hours a day. I use the personal assistant service. Fortunately, I have been availing of the Irish Wheelchair Association service in Dublin for over 12 years. New people are coming in all the time. As Ms Power said, this area is crucial. We need to consider the role of the whole family network. Parents are left to deal with these issues. Many parents are the main carers. People with the condition are not becoming independent — they are depending on their parents. That is a big area for us.
I will refer the questions about research and the national statement to Dr. Wood.
Dr. Wood
I will touch on some of the points which have been raised. The establishment of our consortium was a very unusual thing to do, scientifically. It is not often that researchers from a number of institutions and laboratories decide to co-operate with a single aim, rather than to work against each other competitively. While it is extremely unusual, it is working very well. Holland is the only other place in the world where a similar consortium is working. We are working closely with the Dutch consortium on the way we design the trials, so that they will be comparable. They are using slightly different chemicals, however. It is hoped that we will learn different things from each trial, but they should be comparable at the end.
As I have already said, the first trial will involve injecting little chemical drugs into a single muscle. That is why those of us in the regulatory committees in the UK felt we could not recruit patients under the age of ten. Such a procedure would not be of any therapeutic value to these children. It was felt that the children really needed to have an understanding if they were to be able to consent to undergo a trial that would benefit other people, rather than them. We will be able to recruit younger children for the second trial, which is a systemic trial that might offer some benefit to them. I do not think there will be any problem with recruiting younger children for that trial, as their parents will be able to give consent on their behalf. People felt that the children really needed to understand that the first trial, which will begin this year, would not benefit them.
The second trial, which is planned for 2008, will involve testing a systemic therapy on the whole body. It is hoped that the results of that trial will start to come through in 2009. We should have some idea within the next three years of whether a therapy that treats all the muscles in the body is feasible. We will be able to open out a bigger trial after that. The first trial will involve nine patients and the second trial will involve 20 or 25 patients. We hope to be able to recruit some patients in Ireland for the second trial, especially as MDI has shown a commitment to the process. The numbers here are such that we hope to be able to find some suitable patients from Ireland to include in the trial. It is difficult to find suitable patients, for a number of reasons. We have to find exactly the right genetic mutation that is treatable by our chemical drugs in each instance. The drugs have to be tailored to the patients. We need to search quite widely to find the nine or 25 patients we need.
I have spoken about the timeframe. Deputy Connolly asked about stem cells. That work is being actively pursued, not in my university or my research group but by other people throughout the world. It does not seem quite as promising as the moment because the researchers will ultimately need to face the challenge of getting the stem cells to every single muscle in the body, which is like what we are trying to do. It is more difficult to do that with cells than with small chemical drugs. That is the problem faced by those working with stem cells.
I also asked about the work being done in Ireland.
Dr. Wood
Yes. That sounds excellent. A number of Irish specialists are experts on the pathology of the disease. When we start to take biopsies from the treated patients, we will need to recruit pathologists to the study. I think that is where some of the specialists in Ireland could be very helpful.
Ms Pickering
Many of the members of MDI go to the genetic clinic at Our Lady's Hospital for Sick Children, which offers an absolutely essential service. There is a waiting list for that. Most of the boys with Duchenne are probably being diagnosed at a fairly early stage. If it is known to be in the family, perhaps it will be identified earlier. If it is not known to be in the family, perhaps they will be sent for diagnosis when symptoms start appearing between the ages of three and five. As it is the most common form of muscular dystrophy, it is diagnosed in a more timely fashion than some of the other types of muscular dystrophy which are much rarer.
Many of the registered members of MDI do not know what type of muscular dystrophy they have — they were never given an actual diagnosis. That obviously makes it difficult for them. If they are intending to have families, they do not know how their type of muscular dystrophy was inherited and they do not know whether they will pass it on to any children they might have. I often hear from people who tell me about an uncle, for example, who died many years ago and they did not really know what was the cause of his death. If a woman is coming up to the time when she is planning to get married and thinking about having children, and she suddenly learns that her uncle died from this condition, she might have to try to access genetic counselling to find out if there is a possibility that she might pass on Duchenne muscular dystrophy to any children she might have. Genetic counselling is, therefore, a major issue. The service in Our Lady's Hospital is very good.
Is there a delay in getting an appointment?
Ms Pickering
I believe it takes more than six months to be seen. Some of those who have contacted us are in an emergency because they have found out they are pregnant and are not sure if they are carriers. In an emergency it is possible to be seen earlier but the service is so oversubscribed that it takes at least six months to get an appointment.
Life expectancy is fairly similar to other regions but our multidisciplinary clinics are at an earlier stage. For example, the muscle centre in Newcastle-upon-Tyne has been in operation in the United Kingdom for several years. Heart and respiratory monitoring is still at an early stage here. As Mr. Mooney indicated, this service is having a major influence as it is now more widely available as is information on assisted ventilation. A clinic in Crumlin opened this summer to monitor the heart function of boys with Duchenne muscular dystrophy. It was established because parents who had read the research asked whether their boys should have their heart checked and whether they needed to take drugs. It is due to them that the Crumlin clinic is up and running. We fully support multidisciplinary clinics.
I thank the delegation for its presentation. The joint committee will try to relay the issues it has raised, particularly in the area of funding, to the Department when it makes recommendations in its presentation.
I must apologise for leaving before the next presentation. I am acting Whip today and must attend to other business.
Sitting suspended at 10.22 a.m. and resumed at 10.25 a.m.