AGSD (UK) Family Conference, October 16th 2005
Pompe Workshop Report
Allan Muir, Pompe Representative, AGSD(UK)
On October the 16th this year we held our annual AGSD (UK) family conference in Milton Keynes. For the Pompe Workshop we had a good number of families present and hopefully I left enough time in and around the programme for them to chat and swap stories amongst themselves. We had the added advantage this year of sufficient sponsorship to allow us to put on a conference dinner the previous evening, adding to the sociability of the event. I would like to thank Genzyme Europe for supporting our 2005 conference so generously.
After the AGSD (UK) AGM we had an interesting talk from Professor Smit on the bloodspot screening program in The Netherlands. Newborn screening for Pompe Disease in the UK is one of our major goals once the treatment gains regulatory approval, so hearing about the decision process in Holland helped us understand our own situation.
This year our Pompe Workshop was designed to concentrate more on the immediate needs of late-onset patients and less on crystal gazing into medical advances. The presentations are summarised below:
Pompe Programme Update
Julie Kelly - Senior Director, LSD Business Unit, Genzyme Oxford.
Julie gave a comprehensive overview of the trials progress. For each trial Julie explained their rationale, design, inclusion/exclusion criteria, endpoints and some of the latest results. There will not be a Late-onset Treatment Study trial site in the UK and so our members are not expected to participate in it, but we do have one 15 year-old in the Mini-LOTS trial in Rotterdam. The results of this trial will be invaluable in showing the regulatory bodies the efficacy of Myozyme in late-onset patients using enzyme from the 2000 litre bioreactors.
The Expanded Access Programmes were discussed, ongoing for infants and reviewed quarterly for new late-onset applicants. Sadly there is still very little material available for late-onset patients. Currently over 70 patients (all ages) in 14 countries at 38 sites are receiving Myozyme through the EAP.
On manufacturing we were informed about the new facility opened in Geel, Belgium that will produce Myozyme from two 4000-litre bioreactors; production is anticipated for 2009.
Julie ended by announcing that Genzyme (UK) plan to hold a Physicians Day in Oxford on May 23rd 2006 in anticipation of the European Medicine Agencys (EMEA) decision on Myozyme in March 2006.
Outcome of the ENMC Meeting and Future Therapies for Muscle Diseases
Prof Francesco Muntoni FMedSci
Professor of Paediatric Neurology, Department of Paediatrics, Imperial College London (ICL), Hammersmith Hospital.
Prof Muntoni has taken a special interest in Pompe Disease, his specialities lie in clinical and experimental studies in paediatric neurovascular diseases, muscular dystrophies dilated cardiomyopathies; gene therapy of muscular dystrophies and the genetic basis of muscular dystrophies.
He gave an outline of the ENMC Pompe Disease Workshop organised by Prof Volker Straub and Ans Van der Ploeg earlier this year. The meeting was designed to define standards of medical management in Pompe Disease; Volker Straub will be publishing his report on this very soon. The UK National Health Service (NHS) has recently set up six centres for the Diagnosis, Management and Treatment of Lysosomal Storage Diseases (LSDs); the outcome of this meeting will be an invaluable resource for these centres.
Prof Muntoni also discussed future therapies; in particular he explained current thinking in stem-cell research for muscle regeneration:
Satellite cells are quiescent cells under the basal lamina of muscle fibres that are responsible for muscle regeneration. They are a major source of muscle regeneration; they can be described as a tissue-specific stem cell. It is not known if they self-renew, or are replenished from other stem cells present in muscle or the blood circulation. The relative contribution of satellite cells and other stem cells to functional muscle regeneration has been under discussion for some time but some progress is currently being made.
Previous efforts of using myoblast transplantation in muscular dystrophy have not been successful, several studies have concluded that:
a. most of the transplanted cells do not survive long
b. those cells that survive are not as active as one would have hoped
More recent studies have clarified some fundamental aspects of the biological properties of muscle satellite cells, and new studies are being planned to overcome the previously observed difficulties with myoblast transplantation.
Commenting on how satellite cells fulfil the function of stem cells he reported that when one isolated fibre is transplanted into irradiated host muscle it can make more than 100 regenerated fibres. Following grafting of one isolated fibre, many more satellite cells are formed than were originally transplanted. When the regenerated muscle is re-injured by injection of snake venom, these donor satellite cells are capable of extensive regeneration. The mouse satellite cell therefore fulfils the definition of a stem cell (it has the capacity to differentiate, self-renew and provide long-term regeneration).
Current research at
Results from the IPA/ Erasmus MC Pompe survey
Update on Enzyme Replacement Therapy studies
Marloes Hagemans MSc. and Dr. Nadine Van der Beek, Erasmus MC
Marloes started the presentation with an overview of the clinical manifestations of Pompe Disease before describing the first IPA/EMC Pompe Survey. The research goals for this study were:
- Describe the natural course of late-onset Pompe disease
- To Describe the disease severity
- To survey the use of medical care
- To develop and test measurement scales for assessing disease severity and clinical follow-up.
A total of 303 patients returned questionnaires for the survey that was initially piloted in The Netherlands before being translated and expanded to include the international patient population.
A follow-up study has been designed which is sent to patients 3 years after their baseline survey (2 years in Holland). Dutch patients have completed their questionnaires and the international follow-up is now in progress. UK forms have recently been distributed.
Marloes showed some of the analysis that has been possible from the data, here is her short summary:
Pompe disease is a spectrum:
- First symptoms may appear at any age
- Mild and severe patients in every age group; disease severity depends on disease duration and not on age
- Mobility and respiratory problems may exist separately
- Respiratory function should be measured periodically in all patients
- Subgroup of patients under 15 years with more rapid course
- Intensive follow-up & timely intervention
Pompe disease is a progressive disorder, in two years:
- Mobility problems increased
- Ability to perform functional activities decreased
- Need for artificial ventilation increased significantly
- Handicap/participation scores decreased significantly
- Four patients died at a relatively young age
Marloes stressed the importance of this data; it leads to a better understanding of the disease impact on patients lives and supports the treatment of late-onset patients. The analysis is an important resource for patients, physicians, nurses, paramedics, and policy-makers, and will help in our calls for reimbursement for expensive drugs from health-care providers.
Dr. Nadine Van der Beek followed on by describing a Prospective Observational Study designed to yield the following:
- A better insight spectrum of disease and disease progression
- Genotype-phenotype correlation
- Advice about supportive measures
Together with results from the ERT trials data, the study should also decide, in respect to future enzyme replacement therapy (ERT):
- Which patients need ERT?
- When to start ERT?
- The effect of ERT in larger patient population?
This study is on-going, 27 patients are enrolled and undergo a number of muscle function tests, lung function tests and laboratory assessments. They are followed up every six months.
Nadine then presented results from the ERT studies at Erasmus MC. Since 1999 they have treated 7 infants (0-1yr), 9 late-onset children (2-17yrs) and 4 late-onset adults. We were treated to some videos showing the outstanding success of ERT in infants and children. The conclusions thus far for infants are:
- The outcome of ERT in classic infantile patients is to some extent determined by age, but more so by the state of disease; early start of treatment is essential
- Respiratory failure is difficult to restore
- ERT increases survival significantly
- ERT shows a good response to the heart
For late-onset Pompe, the conclusions are:
- Significant effect on pulmonary function, however it is difficult to restore pulmonary function if patients are severely affected.
- Effect on motor performance is highly dependent on the condition of the patient at start of treatment
- Patients experience an improvement in quality of life
More data is required in late onset patients to learn the full effect and limits of ERT on pulmonary and motor function. The Mini-LOTS trial for youngsters between 5 and 18 will provide much needed data as will the LOTS study just starting in Rotterdam as well as 3 sites in the USA and one in France.
A multidisciplinary approach to the management of patients with neuromuscular disorders
Dr David Hilton-Jones
Oxford Muscle & Nerve Centre ,Radcliffe Infirmary
Dr. Hilton-Jones is a Neurologist who runs one of the five Specialist Centres supported by funds from the Muscular Dystrophy Campaign (MDC). Other centres are at the Hammersmith Hospital (Prof Muntoni), Newcastle (Prof Volker Straub), and the Scottish and Welsh Muscle Networks. Pompe sufferers attending the Oxford centre age between 41 and 67 and he discussed the difficulties of caring for patients whos condition varies so much. He commented that historically the UK has had a very small number of Neurologists (300 serving a population of 60 million compared with The Netherlands who have 1600 serving 16 million people). Traditionally, the experiences of patients with very rare disorders have not been good; doctors would not have a special interest, a different (junior) doctor would be seen at each visit and the patient would receive a random or late referral to specialist centres.
The MDC centres are able to offer great improvements over the traditional care; the muscle centre at Oxford holds two "informal and fun" clinics per week and is run by a team of 5 staff:
- Consultant (David Hilton-Jones)
- Nurse (Eve Goodger)
- MDC Care Advisor (Jane Stein)
- Physiotherapist (Jane Freebody)
- Genetics counsellor (Gael Bretz)
The hospital supports other needs of neuromuscular patients, for example:
- Surgery (spinal, tendons)
The MDC also supports a Neuromuscular Research Fellow who spends 70% of his time in research and 30% developing clinical skills. His role includes selecting patients for research and bringing research developments rapidly to the clinic for the benefit of patients. A laboratory scientist and secretary/administrator complete the team of staff supported by the MDC.
Jane Stein - MDC Care Advisor
Oxford Muscle & Nerve Centre
Radcliffe Infirmary, Oxford
Jane Stein gave a very comprehensive list of concerns and needs of patients with neuromuscular disease. She indicated how each could be tackled and how the Muscular Dystrophy Campaign can help with advice on each of the areas below:
- Equipment at Home
- Riser Arm chairs
- Bathroom fixtures
- Kitchen equipment
- Housing Adaptations
- Social Services O.T.s
- MDC Adaptations Manual
- Other families
- Council tax banding
- Which benefits may be relevant?
- How do I get information about benefits?
- How do I apply?
- What is the appeals procedure?
- Obtaining a wheelchair
- Wheelchair services
- Voucher schemes
- Charitable organisations
- Red Cross (on loan)
- Vehicles and driving
- Mobility Road shows
- Blue Badges
- Social Care
- What is "social care?"
- Who provides it?
- How do I access it?
- How is this care financed?
- Health Care
- What is "health care?"
- Who provides it?
- How do I access it?
- Who pays for it?
- Further education
- Adult education
- Support in finding work
- Access to work
- Workplace rights
For more information on these topics please refer to the MDC website (http://www.muscular-dystrophy.org). Alternatively you can telephone them on:
Muscular Dystrophy Campaign
7-11 Prescott Place
Jane Freebody - Chartered Physiotherapist
Oxford Muscle & Nerve Centre
Radcliffe Infirmary, Oxford
Jane Freebody works part time at the Oxford Muscle Clinic for adults with neuromuscular diseases and also part time with children in the community. She has a strong interest in sport and the benefit of exercise and has been involved with sport for the Disabled for many years. She is an internationally accredited classifier for athletics with the International Wheelchair and Amputee Sports association.
She recently visited Brazil to teach the classification system to their National Federation and is involved in a pilot project looking at the effect of exercise in adults with Muscular Dystrophy.
Jane described how an individual patient would be assessed at the Muscle Clinic, gathering information on the individuals lifestyle, work, mobility, activities and specific exercises. Assessments would be made of posture, mobility, gait, muscle power/weakness and any functional limitations. These would lead to an exercise programme tailored to the individual. Jane did, however, give some general advice on how to maintain the muscles by staying active. She suggested that we should all exercise five times per week; each session being of moderate intensity and last for about 30 minutes. The exercise should result in the body warming up a little and faster breathing. Exercise shouldnt be strenuous and could include any activity: walking, gardening, swimming, shopping or housework, for example. Many patients find mobility aids useful, such as walking sticks, walking poles (better as the handles are much higher than sticks), elbow crutches or wheeled walkers.
Information and Advice Line Officer
Muscular Dystrophy Campaign
The AGSD (UK) has employed the services of Helen for one day per week to help with some of the important work that had overwhelmed the voluntary staff (guess who!). The relationship with Helen brings with it much more than her administrative help, it brings the two charities together and helps the AGSD (UK) support its members through the many services of the MDC, as described above by the Oxford team and in Helens own presentation.
Helen gave a very full (and very animated) account of the services offered by the MDC and I dont propose to repeat it all here, I suggest that UK Pompe sufferers should go to the website or join the MDC by contacting them with the details I gave above (Jane Steins talk). Membership is free and on joining you will receive a membership pack detailing many of the services offered.
Helen is currently surveying all the (UK) Late-Onset Pompe Sufferers known to the AGSD (UK) and once this is complete we will have a better understanding of the needs of the Pompe community in the UK, and what we might do to try to improve the situation.
Allan Muir, Pompe Representative, AGSD (UK)
The final session was my account of the years events and the current concerns we have. Much of what I had to say is soon to be published in our next Pompe Update and so I wont repeat it here other than to say that we are encouraged by the messages emerging from our National Health Service (NHS) regarding funding for ERT, but we are very concerned that the label for Myozyme may not initially cover late-onset patients. There would seem to be little prospect of the NHS funding Myozyme off-label (prescribed for an adult when the therapy is only approved for infants).
I took the opportunity to advertise the latest IPA publications, now available on the IPA website: www.worldpompe.org. Pompe Connections is a series of brochures offering a wide range of information for Pompe patients.
I am very pleased to announce that brothers Corrie and Luke Fraser accepted editorial responsibility for the Pompe Bulletin. It has distressed me this year that I have been unable to find time for this important publication. With all that is going on in the Pompe world currently, we need to have good and regular communication with our membership, hopefully now we will be able to achieve that aim.
Finally I would like to thank all those who gave up their valuable spare time to join us in Oxford, meet our members and enlighten us with their presentations.