Arthritis Research UK Submission to House of Lords Committee on Science and Technology Inquiry: Regenerative Medicine

Transcription

1 September 2012 Arthritis Research UK Submission to House of Lords Committee on Science and Technology Inquiry: Regenerative Medicine 1. Arthritis Research UK welcomes the opportunity to respond to the House of Lords Committee on Science and Technology Inquiry on Regenerative Medicine. 1 Through the examples in this submission we provide a brief overview of our charity s involvement in this area, and views of some of the researchers we support. We would be pleased to expand on the points below, and to provide further information to the Committee as oral evidence. 2. Arthritis is the UK s fourth largest medical research charity. Our vision is a future free from arthritis. Our remit includes arthritis and musculoskeletal conditions, which are disorders of the joints, bones and muscles including back pain along with rarer systemic autoimmune diseases such as lupus. Together, these conditions affect around ten million people across the UK and account for the fourth largest NHS programme budget spend of 5 billion in England. 2 Arthritis is the biggest cause of pain and disability in the UK and each year 20% of the general population consult with their GP about a musculoskeletal condition. 3 As a charity we fund research, provide information to patients and educational resources for healthcare professionals. 3. Our research strategy includes the goal that by 2020, working with our partners, we will Be at the forefront of international efforts to harness the potential of stem cells. More specifically, the charity will encourage a well developed programme of research in the UK with the necessary expertise, investment and infrastructure to carry out internationally competitive research aimed at using the body s own cells to replace worn out joints in disorders such as osteoarthritis Osteoarthritis is the most common type of arthritis, affecting 8 million people nationwide. There are, for example, over 5.5 million people in the UK with painful knee osteoarthritis, and as age and obesity are risk factors for knee osteoarthritis the prevalence of this condition is predicted to increase. Whilst healthy joints move painlessly due to an even layer of smooth cartilage coating the ends of bones, in osteoarthritis cartilage becomes thinned and pitted, and can wear away completely, causing severe pain and disability. 5 Regenerative medicine in musculoskeletal conditions 5. Regenerative medicine refers to the use of methods to replace or regenerate human cells, tissues or organs to restore or establish normal function including cell therapies, tissue engineering, gene therapy and biomedical engineering techniques In the musculoskeletal field, there are a number of disorders which are the result of trauma and degeneration where engineering replacement tissues has the potential for substantial benefit. In addition to osteoarthritis, there are unsolved problems including sports injuries to tendons, ligaments and cartilage, as well as fractures with delayed healing. Unlike other areas of medicine, tissue engineering requires that the new tissues 1 House of Lords Committee on Science and Technology (July 2012) Inquiry on Regenerative Medicine: Call for evidence 2 Department of Health (December 2011). England level programme budgeting data Arthritis Research UK National Primary Care Centre, Keele University (October 2009). Musculoskeletal Matters. 4 Arthritis Research UK (December 2010).Working in partnership towards a future free from arthritis, Our research strategy For information about osteoarthritis see -information/conditions/ osteoarthritis.aspx 6 House of Lords Select Committee on Science and Technology (July 2012) Inquiry on Regenerative Medicine: Call for evidence 1

2 have the same mechanical (structural) characteristics properties as well as the functional properties of the original tissue. 7. Approaches to restore damaged musculoskeletal tissues are dependent on the development of effective solutions involving tissue scaffolds, biological factors and cellular strategies. This brings unique scientific and regulatory challenges to regenerative medicine in musculoskeletal conditions. Whilst some new therapies in development are based on differentiated stem cells, it is also important to recognise that other cell types may also be used. The research base How does the UK rank internationally in the scientific field of regenerative medicine? 8. The use of regenerative medicine for musculoskeletal conditions is an area in which the UK has considerable expertise, and there are examples in this field in which the UK has established an international lead. For example, the identification and characterisation of a population of cartilage progenitor cells in human articular cartilage was achieved in the UK. 7 As far as we are aware, the Arthritis Research UK Tissue Engineering Centre is one of the first initiatives in the world dedicated to the development of regenerative medicine approaches, including adult stem cell engineering, for disorders such as large joint osteoarthritis. It has the ultimate goal of developing interventions which can be delivered widely and affordably within the NHS and can either reduce or postpone the need for surgery such as joint replacement. 8 Where does the UK have strengths and weaknesses in the field? 9. Progress in regenerative medicine requires multidisciplinary expertise, including the involvement of basic scientists, engineers and clinicians. Such cross-disciplinary working, and the ability to involve teams in both hospital and academic settings, can be a UK strength. The Arthritis Research UK Tissue Engineering Centre is a multi-site centre of excellence which brings together experts including cell biologists, material engineers and orthopaedic surgeons, working collaboratively to deliver clear research themes. 10. Academic clinicians play a key role in the translation of scientific discovery through delivery to the patient via the clinic. It is important to ensure that the UK develops and supports sufficient academic clinicians in this field to enable translation of research and subsequent implementation within the health service. Who are the major funders of research in the field of regenerative medicine? What funding is available to support this research? 11. In the UK there is a strong involvement of academia, charities and the NHS in the field of regenerative medicine, with a range of funders supporting key national facilities. 9 As a charity, Arthritis Research UK funds a range of pre-clinical and clinical research in regenerative medicine. The following sections provide examples of the research we support. 7 Williams et al. (2010) Identification and Clonal Characterisation of a Progenitor Cell Sub-Population in Normal Human Articular Cartilage. PLoS ONE 5(10): e doi: /journal.pone Examples include the Tissue Engineering and Regenerative Medicine Centre (TERM) at Imperial College London, and the Wellcome Trust-Medical Research Cambridge Stem Cell Institute. 2

3 12. Arthritis Research UK Tissue Engineering Centre Launched in October 2011, the Arthritis Research UK Tissue Engineering Centre is led by Newcastle University and is based at four sites across the UK: Newcastle University, the University of Aberdeen, Keele University/the Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, and the University of York. It brings together leading clinicians, engineers and biologists from research and clinical groups. The Centre aims to regenerate bone and cartilage by using patients own stem cells to repair the joint damage caused by osteoarthritis. It is funded by a core grant of 2.5 million over five years from Arthritis Research UK with a further 3.4 million pledged by the four participating universities. 10 This is also an example of the role that funding from an independent charity can play in supporting cross-institutional collaboration. 13. Clinical Trials Arthritis Research UK supports work including: REACT: Arthritis Research UK has funded clinical research to review and follow a cohort of patients treated for cartilage defects with autologous chondrocyte implantation (implantation of the patient s own cartilage cells) with a follow-up of up to 15 years. There is much to learn from this cohort, including for example, the factors which predict the 80% of patients who benefit from such approaches, and factors which associate with those who do not report improvement. 11 ASCOT: This future prospective randomised trial will compare chondrocyte and mesenchymal stem cell treatment for early osteoarthritis of the knee. A third group in the trial will be treated using both cell types, as there is evidence that the combination may be better than either cell type alone. 14. Project Grants and Fellowships Arthritis Research UK supports a number of Project Grants and Strategic Fellowships which use regenerative medicine approaches to address a range of different research questions, for example: Research to address important questions which will help in the development of a stem cell therapy for the treatment of intervertebral disc degeneration, one of the major causes of low back pain. 12,13 Research to determine how stem cells regenerate cartilage in osteoarthritis. 14 Research to explore whether embryonic stem cells can generate the cells needed to repair joint cartilage. 15 Application of the science What are the current applications of the science of regenerative medicine for the treatment of disease in the UK and internationally? 15. The majority of applications in musculoskeletal health have been for cartilage repair, with some work focusing on bone regeneration. Research to restore cartilage has also led to progress in other fields. For example, Arthritis Research UK Professor of Rheumatology

4 and Tissue Engineering at the University of Bristol, Professor Anthony Hollander, developed techniques to form human cartilage from a patient s own stem cells. This technology contributed to an international collaboration to grow the first trachea (windpipe) for transplant from a patient s own cells. 16 What potential does regenerative medicine hold to treat disease in the next 5-10 years? 16. As in many biomedical research fields, it is important to recognise that the timescales between initial research discoveries and the delivery and take up of health interventions are often long (up to decades), variable and difficult to predict. 17. However, in the next 5-10 years one of the aims of research funded by Arthritis Research UK is to develop the capability to treat the joint damage caused by osteoarthritis at an earlier stage. If successful, it is hoped that these techniques slow down the progression of the disease and therefore delay the requirement for joint replacement. Such approaches are needed because, although joint replacements are often highly successful, joint replacements can, despite variations in design, fail over the lifetime of the younger active patient. Techniques that can delay the first joint replacement may prevent joint revision in later life which can be costly and carry significant risks. 18. The future work of the Arthritis Research UK Centre for Sports and Exercise Injuries will also encourage the development of cellular therapies for a range of musculoskeletal conditions. 17 For example, rupture of the cruciate ligament surrounding the knee is a common sporting injury which can lead to osteoarthritis. Current therapy to treat cruciate ligament damage relies on a surgical approach. However, we anticipate the development of innovative and more effective approaches which may involve cellular, or combined cellular and surgical, techniques. Future collaboration between Arthritis Research UK s centres of excellence will facilitate this work. Barriers to translation [Are actions sufficient] to encourage the safe development of regenerative medicine treatments and to overcome the significant regulatory barriers and challenges to innovation? 19. The cost and complexity of clinical trials governance in regenerative medicine is significant, and due to the evolving nature of the process can be difficult to predict in terms of time and money. There is a need for effective partnerships between the NHS and research groups for clinical trial delivery. On-going challenges include: The complexity of the regulatory environment for therapeutic products which involve both cellular material and non-biological components (scaffolds). A lack of flexibility in regulation, particularly for pilot studies. Complexity of licensing for cell therapy products. Cost of license applications and inspections is great and difficult to predict accurately. A lack of Qualified Persons with cellular therapy expertise to assist the process of approval by the Medicine and Healthcare products Regulatory Agency (MHRA), and on-going governance of cell production. Training in quality control of cell production could usefully include cell biologists as well as pharmacists. A current European Union Framework Programme 7 project Academic GMP aims to address some of these points Macchiarini et al (2008)Lancet.13;372(9655): leases/2011/july/national-centre-for-sports-injuries.aspx

5 European regulation of advanced therapy medicinal products (ATMPs). Current EU legislation hinders development of novel cellular therapies due to the need for expensive good manufacturing practice (GMP) compliant processes which are inflexible and based on drug therapies. 20. Additional barriers to translation include: Difficulty in securing agreement for the allocation of the excess treatment costs component of research costs associated with clinical trials. Although risk can be minimised, the risks of application of new treatment may not be known until a trial takes place. Researchers are personally responsible for the accuracy of data collection and analysis and may not have extensive resources to ensure this accuracy. Fear of litigation can therefore act as a barrier to translation Barriers to commercialisation What business models are most appropriate to support the development of regenerative treatments? 21. Models of working which support collaboration between academic groups are important, and charity funding can be an important mechanism in bringing groups together in this way. Many cellular therapies are developed and pioneered in academia. It is important that investment from the pharmaceutical industry complements charity, NHS and Government support - closer integration of the sector, bringing a two-way model between academic and the industry sector would be beneficial. Additional means of supporting the sector include: Pharmaceutical company investment into earlier stages of research. Initiatives to bring together infrastructure and academia in a critical mass. International comparisons What could the UK learn from its competitors about supporting the development and commercialisation of regenerative medicines? 22. In relation to regenerative medicine approaches in musculoskeletal health, there is strong support for the advancement of techniques involving cell therapy related operations in countries including Belgium and the Netherlands. There may be opportunity to learn from the work in these countries. Contact details 23. We are very grateful to the following for their contributions to this response: Professor Andrew McCaskie, Professor of Orthopaedic Surgery, Newcastle University Dr Sally Roberts, Spinal Studies & ISTM, Keele University Professor Anne Dickinson, Professor of Orthopaedic Surgery, Keele University Professor James Richardson, Professor of Orthopaedic Surgery, Keele University I hope this information is helpful. Please contact the policy and public affairs team at the address below if require further information. 5

6 Yours sincerely, Professor Alan Silman Medical Director, Director of Research Strategy and Policy Arthritis Research UK For further information on this submission please contact: Dr Laura Boothman Policy Manager Arthritis Research UK 41 Portland Place, London, W1B 1QG Tel , Mob Registered charity in England and Wales No , Scotland No. SCO41156 A Company registered in England and Wales and Limited by Guarantee No