Regenerative medicine - Science and Technology Committee Contents


Chapter 2: Definitions and examples

What is regenerative medicine?

8.  The term "regenerative medicine" is used to refer to methods to replace or regenerate human cells, tissues or organs in order to restore or establish normal function.[4] This includes cell therapies, tissue engineering, gene therapy and biomedical engineering techniques, as well as more traditional treatments involving pharmaceuticals, biologics and devices. In Boxes 1 and 2 we set out some key definitions.

BOX 1

Definitions

ATMP (Advanced Therapy Medicinal Products): innovative, regenerative therapies which combine aspects of medicine, cell biology, science and engineering for the purpose of regenerating, repairing or replacing damaged tissues or cells.[5]


Biologics: medicinal products that contain one or more active substances made by or derived from a biological source.[6]


Cells: the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialised functions such as secretion of hormones, information processing, defence against disease, and transport of nutrients. Cells also contain the body's hereditary material and can make copies of themselves.[7]


Cell therapy: administration of cells to the body to the benefit of the recipient.[8]


Gene: single unit of genetic material located in the cell nucleus in chromosomes (long, threadlike structures in each of the body's cells that contain DNA). Genes contain the genetic information that influences almost all the characteristics of the individual from hair colour to risk of dying of heart disease.[9] Some genes code for proteins, the body's building blocks; others act as control switches, and others do not have any known function.


Gene therapy: deliberate introduction of genetic material into cells to the benefit of the recipient.[10]


Scaffold: support, delivery vehicle or matrix for facilitating the migration, binding or transport of cells or bioactive agents.[11]


Tissue engineering: use of a combination of cells, engineering, materials and methods to manufacture ex vivo (outside the living body) living tissues and organs that can be implanted to improve or replace biological functions.[12]


BOX 2

Cell definitions: types, potency and therapy types

Allogeneic: where donor and recipient cells are from different individuals.[13]


Autologous: where cells are from the same individual.[14]


Differentiation: the process whereby an unspecialised embryonic or other cell acquires the features of a specialised cell such as a heart, liver, or muscle cell. Differentiation is controlled by the interaction of a cell's genes with the physical and chemical conditions outside the cell, usually through signalling pathways involving proteins embedded in the cell surface.[15]


Multipotent: cells that have the ability to develop into a limited number of specialised cell types.[16]


Pluripotent: cells that are capable of differentiating into all tissues of an organism, but are not alone capable of sustaining full organismal development.[17]


Stem cells: cells with the ability to divide for indefinite periods in culture and to give rise to specialised cells.[18]


Embryonic stem cells: undifferentiated cells derived from a pre-implantation embryo (an embryo of about 150 cells produced by cell division) or blastocyst that is pluripotent.[19]


Induced pluripotent stem (iPS) cells: human embryonic stem cell-like cell that is produced by reprogramming a cell to a state of pluripotency.[20]


CURRENTLY AVAILABLE TREATMENTS

9.  Regenerative medicine is explained well by illustration. The following examples are a selection of treatments that are currently available. There are only two regenerative medicine treatments with European Union Marketing Authorisation (central approval which is binding in all Member States): glybera, a gene therapy to treat lipoprotein lipase deficiency (a rare disease in which patients have a defect in the gene encoding an enzyme responsible for breaking down fats); and ChondroCelect, an autologous cell therapy where a patient's cartilage cells are biopsied, grown and expanded in the laboratory and used to treat cartilage defects in knees.[21] ChondroCelect has been used in the UK in private healthcare settings but is not available through the NHS as NICE has not completed its evaluation, meaning no centrally agreed level of reimbursement can be offered.[22] Glybera has only recently been approved for use.

10.  Bone marrow transplantation is widely recognised as the original stem cell therapy.[23] A bone marrow transplant involves taking healthy stem cells from the bone marrow of one person and transferring them to the bone marrow of another (or, in some cases, a patient's own healthy bone marrow).[24] Transplants are often used to treat conditions, such as leukaemia, which damage bone marrow so that it is no longer able to produce normal blood cells. In the period 2004-09, 14, 366 haematopoietic (giving rise to blood cells) transplants were performed in the UK,[25] demonstrating that this treatment is both available now in the UK and is undertaken extensively.

11.  The Scottish National Blood Transfusion Service (SNBTS) developed and operates a UK-wide pancreatic islet transplantation service for patients with type one diabetes who have poor glycaemic awareness (problems recognising when their blood sugar levels become dangerously low). Islet cells, which make and release insulin, are extracted from the pancreas of a deceased donor, isolated and then transfused into the liver of a recipient patient to restart the body's insulin production in an experimental treatment. This procedure was carried out 61 times in the period 1 December 2010-30 November 2012.[26] Severe hypoglycaemia was reduced by >95% among patients who have received the treatment, and overall insulin requirement was halved, with a significant numbers of patients becoming insulin-independent.[27] There is great need for such a treatment, with up to 2, 000 of the 28, 000 people with type one diabetes in Scotland alone struggling to recognise low blood sugar levels,[28] but the number of transplants is limited by supply.[29]

12.  Regenerative treatments are also used to help patients with burn injuries. Replacement skin cells can be grown from a postage stamp-sized sample of a patient's healthy skin to replace the top layer of skin (epidermis) for patients with severe burns. Cells from the skin sample are separated and grown by a process called tissue culture, which involves feeding the cells with specific nutrients and maintaining strict environmental controls so that the cells multiply to form sheets of skin. They can be grown on a layer of irradiated mouse cells. A surgeon then undertakes a procedure which covers (grafts) the lost or damaged skin. This grafted skin replaces the patient's top layer of skin in order to help burn wounds heal.[30]

TREATMENTS LIKELY TO BE AVAILABLE IN THE NEXT FIVE YEARS

13.  Having considered the limited number of treatments currently available in the UK we asked which treatments were likely to be widely available in the next five years. Regener8 (an organisation seeking to build collaboration between industry and universities) observed that treatments which supported the body's own regeneration and repair mechanisms, such as treatments that use scaffolds and matrices, were more likely to be available in the next few years than ATMPs, as were treatments that required minimal manipulation of a patient's own cells.[31] The BioIndustry Association (BIA) (a trade association for innovative enterprises involved in UK bioscience) observed that treatments likely to be available in five years would need to have regulatory approval already, or to be in late stages of clinical trials.[32] We considered some examples of treatments in the later stages of clinical development which showed some promise.

14.  Clinicians at Moorefield's Eye Hospital and the company Advanced Cell Technology (ACT) are trialling a treatment for presently incurable eye diseases. They have developed embryonic stem cells (cells from early stage embryos which have the potential to develop into any type of body cell) into a specialised eye tissue type: retinal pigment epithelial (RPE) cells. Many eye diseases are caused by the degeneration or malfunction of this tissue and so replacement of destroyed RPE cells with healthy ones may be an effective treatment option for conditions[33] such as retinitis pigmentosa (a diverse group of inherited eye disorders),[34] age-related macular degeneration (an eye condition where the part of the eye responsible for central vision is unable to function as effectively as it used to, leading to gradual loss of central vision which affects nearly 50, 000 people in the UK)[35] and Stargardt's disease (juvenile macular degeneration).

15.  ReNeuron (a Guildford based stem cell company) is trialling the injection of neural stem cells ("CTX cells") into the damaged brains of elderly patients who are left moderately to severely disabled by an ischaemic stroke (when blood flow leading to, or in, the brain is blocked). There are currently no therapies available for stroke patients who have a stable and fixed neurological deficit. This treatment seeks to reverse the damage caused to the brain.[36]

16.  Imperial College London and the University of Edinburgh are taking part in a European clinical trial using stem cells to treat multiple sclerosis (MS) (a disease affecting nerves in the brain and spinal cord which causes problems with muscle movement, balance and vision).[37] Current treatments for MS are not curative.[38] Mesenchymal stem cells (stem cells derived from a patient's bone marrow) are grown and given back to the patient. It is anticipated that they might help repair the central nervous system.[39]

17.  We consider clinical trials in the UK further, including additional examples, in the next Chapter.

LONG-TERM POSSIBILITIES

18.  The examples above demonstrate that there are exciting potential treatments in the near-delivery end of the pipeline, but regenerative medicine also offers significant hope for treatments for a plethora of diseases in the long-term. Ongoing pre-clinical work suggests that it might eventually be possible to treat Parkinson's disease, cardiovascular disease and diabetes.[40]

The value and importance of regenerative medicine

UNMET MEDICAL NEED

19.  Despite significant progress in medical innovation, there are still many diseases for which there are either no cures or only partially effective treatments. The weight of evidence to our inquiry was that regenerative medicine has the potential to deliver new, innovative therapies, or even cures, where conventional approaches do not provide adequate solutions.[41] Many submissions to the inquiry offered a "health warning", however, that public expectations must be managed as many of these treatments are relatively far from delivery to the wider public.[42] Around 30% of the UK population suffer from a chronic disease,[43] and the World Health Organisation (WHO) estimates that the UK loses $3.4 billion annually in income as a result of deaths from such conditions.[44] Chronic diseases can seriously diminish the quality of life of individuals as well as place great demands on family members and other carers.

ECONOMICS

20.  It is widely acknowledged that the UK's National Health Service (NHS) is facing a funding crisis. According to research from the Nuffield Trust, the increasing cost of chronic disease management, coupled with increased life expectancy, means that "if NHS funding is held flat in real terms beyond this spending review period, the NHS in England could experience a funding gap worth between £44 and £54 billion in 2021-22".[45] Chronic disease management is estimated to account for 70-75% of all UK healthcare costs,[46] and chronic diseases are increasing in prevalence (as illustrated in Table 1 below). An Ernst and Young report observed that the percentage of US GDP spent on healthcare rose from 16% to 18% from 2007-09 and estimated that it would grow to 37% by 2050 without more innovative treatments.[47] The King's Fund estimate that, if healthcare spending and national income increase at similar rates, by the 2070s NHS spending will consume one fifth of total national income, rising to just over half by 2135.[48] Table 1 shows the number of people in the UK affected by specific long-term conditions.

TABLE 1

Number of people in the UK affected by specific

long-term conditions[49]
Long-term condition Number affected by each condition (patients could appear under multiple categories) % change
2006-07 2010-11
Diabetes1, 962, 000 2, 456, 00025%
Coronary heart disease 1, 899, 0001, 878, 000 -1%
Chronic kidney disease 1, 279, 0001, 855, 000 45%
Stroke or Transient Ischaemic Attacks (TIA) 863, 000944, 000 9%
Chronic obstructive pulmonary disease 766, 000899, 000 17%
Heart failure420, 000 393, 000-6%
Epilepsy321, 000 337, 0005%
Dementia213, 000 267, 00025%

A rough indication of the direct costs of chronic disease can be seen in NHS programme budgeting data, which show the amount spent by primary care trusts on different conditions under the old healthcare system but also include some costs for conditions which aren't chronic and do not include the cost of GP contract expenditure which the Department of Health says cannot be estimated at a disease specific level. Table 2 shows the healthcare costs associated with selected conditions.

TABLE 2

NHS programme budget expenditure[50]
Programme Budgeting Category Gross Expenditure (£billion) Expenditure as % of total spend
2006-07 2007-08 2008-09 2009-10 2010-11 2010-11
Cancers and tumours 4.354.96 5.135.86 5.815.43
Disorders of blood 1.031.24 1.261.4 1.361.27
Endocrine, nutritional and metabolic problems 2.132.43 2.532.89 32.80
Mental health disorders 9.1310.28 10.4811.26 11.9111.13
Problems of learning disability 2.492.86 2.933.15 2.92.71
Neurological2.99 3.443.69 4.144.3 4.02
Problems of vision 1.381.60 1.671.93 2.142.00
Problems of hearing 0.330.42 0.420.5 0.450.42
Problems of circulation 6.97.23 7.418 7.727.21
Problems of the respiratory system 3.543.8 4.254.59 4.434.14
Problems of the gastro intestinal system 3.854.1 4.14.58 4.434.14
Problems of the skin 1.551.7 1.812.08 2.131.99
Problems of the musculoskeletal system 3.534.09 4.214.76 5.064.73

21.  The costs of chronic disease are more than those simply of providing healthcare; chronic disease carries significant indirect and intangible costs such as the psychological dimensions of illness. Indirect costs include work absence, reduced productivity, early retirement, premature mortality, and the implications of family members needing to act as carers.[51] It is estimated that productivity losses for employers could be over four times higher than the equivalent medical and pharmacy costs.[52] Regenerative medicine has the potential to cure or provide more effective treatments for a number of chronic diseases, which would be of major benefit to the UK public purse given the rising expenditure on healthcare associated with chronic disease management and related indirect costs.

22.  A further consideration is that regenerative medicine could generate income for the UK economy. In a speech to the Royal Society, the Chancellor of the Exchequer, Rt Hon George Osborne MP, recognised that regenerative medicine could not only "transform current clinical approaches to replacing or regenerating damaged human organs or tissue" but could also be one of "eight future technologies where we [the Government] believe we [the UK] can be the best—where we already have an edge, but we could be world-leading".[53] The UK could see financial returns from foreign patients paying to be treated here, from the development of the domestic regenerative medicine industry and international companies setting up operation in the UK, and from companies paying to conduct clinical trials in the NHS.

Government initiatives

23.  The Government have undertaken and sponsored a number of initiatives to support the field's development.

TAKING STOCK OF REGENERATIVE MEDICINE

24.  The Government published Taking stock of regenerative medicine in the UK in July 2011. The report sought to assess the UK's position in the field internationally, to identify barriers to development and to "lay the ground-work" for a regenerative medicine strategy. The report identified "steep technological, regulatory and strategic barriers to realising regenerative medicine's significant potential" and outlined 10 actions the Government would take to support regenerative medicine in the UK. These included taking steps to "better co-ordinate public investment and leverage funding from private sources; ensure the regulatory framework is facilitating and supported by a strong intellectual property regime, and appropriate standards; provide more clarity and help to get these highly innovative products to patients; and support the sector in the long-term, staying ahead of developments".

LIFE SCIENCE STRATEGY

25.  In December 2011, the Government published their Strategy for UK Life Sciences, which set out actions to protect the UK's status as a world-leader in life science innovation, strengthen the country's life sciences industries and to help to "build a sustainable economic recovery". The three pillars of the strategy were:

(1)  "Building a UK life sciences ecosystem (making it easier for researchers to commercialise academic research, placing clinical research at the heart of the NHS, and empowering patients to participate in research);

(2)  Attracting, developing and rewarding talent; and

(3)  Overcoming barriers and creating incentives for the promotion of healthcare innovation".

26.  Notable actions to which they committed included: an Early Access Scheme "to increase the speed and efficiency of routes to market approval for innovative, breakthrough therapies"; the creation of a more enabling regulatory environment for the adoption of innovative manufacturing technology; establishing a Biomedical Catalyst Fund and a Cell Therapy Technology and Innovation Centre (later to become the Cell Therapy Catapult) (more details in paragraph 50 below); and re-launching an enhanced web-based UK Clinical Trials Gateway to provide patients and the public with authoritative and accessible information about clinical trials in the UK.

STRATEGY FOR REGENERATIVE MEDICINE

27.  The research councils and Technology Strategy Board (TSB) Strategy for Regenerative Medicine, published in March 2012, identified eight key UK strategic objectives which needed to be addressed if the UK is to make the most of its current position:

(1)  investment in underpinning research;

(2)  studying efficacy and safety of the various therapeutic options, including cell transplantation, the stimulation of the body's own repair systems, and the use of acellular products;

(3)  product development: linking early stage regenerative medicine product development with the establishment of manufacturing, transportation and delivery solutions;

(4)  clinical delivery and evaluation: workshops to explore clinical trial challenges in order to establish the most effective trial designs and improve the transparency of the regulatory framework;

(5)  innovation and value systems: investigations addressing issues such as the evolution of new business models, product development mechanisms (including reimbursement and adoption), and open innovation;

(6)  remaining alert to international developments;

(7)  focus: identify key disease areas/therapy types meriting concerted investment; and

(8)  promoting interdisciplinary collaboration: bringing together of strong complementary skills, expertise and infrastructure across disciplines.


4   Op. cit. A brief definition of regenerative medicine. Back

5   Human Tissue Authority (HTA): Advanced Therapy Medicinal Products Regulation and Quality and Safety Regulations, 2008. Back

6   EMA: Questions and answers on biosimilar medicines, 2012, FDA: What is a biological product, 2010. Back

7   National Institutes of Health: Help me understand genetics handbook, 2013. Back

8   British Standards Institution (BSI): Publicly Available Specification (PAS) 84: Regenerative Medicine-Glossary, 2008. Back

9   NHS: Introduction to genetics, 2012: http://www.nhs.uk/conditions/Genetics/Pages/Introduction.aspx. Back

10   Op. cit. PAS 84. Back

11   Op. cit. PAS 84. Back

12   IbidBack

13   IbidBack

14   IbidBack

15   National Institutes of Health (NIH): Stem cell glossary, 2013Back

16   Op. cit. PAS 84. Back

17   Op. cit. Stem cell glossary. Back

18   IbidBack

19   IbidBack

20   Op. cit. PAS 84. Back

21   See:
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000878/human_med_000698.jsp&mid=WC0b01ac058001d124
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002145/human_med_001480.jsp&mid=WC0b01ac058001d124, Q 358. 
Back

22   Cell Therapy Catapult. Back

23   Alliance for Regenerative Medicine. Back

24   NHS Choices: bone marrow transplant, 2012: http://www.nhs.uk/conditions/Bone-marrow-transplant/Pages/Introduction.aspx. Back

25   The British Society for Blood and Marrow Transplantation (BSBMT), the British Society for Haematology (BSH) and the Royal College of Pathologists (RCPath). Back

26   NHS Blood and Transplant Organ Donation and Transplantation Directorate Pancreatic Islet Taskforce: 2 year review of the national pancreas allocation scheme, 2013. Back

27   UK Islet Transplant Consortium: Referral guidelines: islet cell transplantation, February 2013. Back

28   Scottish Government press notice: Diabetes treatment success, 2012. Back

29   Association of the British Pharmaceutical Industry (ABPI). Back

30   See, for example, Epicel: Patient information, 2007: http://www.epicel.com/~/media/Epicel/Files/epicel-patient-information.pdf, FDA: Epicel cultured epidermal autograft, 2007: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm074878.htm. Back

31   Regener8. Back

32   BioIndustry Association (BIA). Back

33   Advanced Cell Technology: Retinal Pigment Epithelial Cell Program: http://www.advancedcell.com/our-technology/act-stem-cell-related-research-pipeline/retinal-pigment-epithelial-cell-program/. Back

34   Royal National Institute of Blind People: Retinitis pigmentosa, 2012: http://www.rnib.org.uk/eyehealth/eyeconditions/eyeconditionsoz/Pages/retinitis_pigmentosa.aspx. Back

35   NHS Choices: Macular degeneration, 2012: http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Introduction.aspx, GE Healthcare. Back

36   ReNeuron: ReN001 for Stroke: http://www.reneuron.com/ren001-for-stroke. Back

37   NHS Choices: Multiple sclerosis, 2012: http://www.nhs.uk/conditions/Multiple-sclerosis/Pages/Introduction.aspx. Back

38   NIH: Clinical trials database-Stem Cells in Rapidly Evolving Active Multiple Sclerosis, 2013: http://clinicaltrials.gov/ct2/show/NCT01606215. Back

39   IbidBack

40   BIA. Back

41   Alliance for Advanced Therapies, Alliance for Regenerative Medicine, Association of British Neurologists, ABPI, CIRM, Dr Paul Kemp, Korea Health Industry Development Industry. Back

42   Miltenyi Biotec, Oxford Stem Cell Institute (OSCI), Research Councils UK (RCUK). Back

43   Department of Health (DH): Long Term Conditions Compendium of Information, 2012. Back

44   World Health Organisation: An estimation of the economic impact of chronic noncommunicable diseases in selected countries, 2006. Back

45   Nuffield Trust: A decade of austerity?, 2012. Back

46   Op. cit. Long Term Conditions Compendium of Information, and Gemmill, M.: Research Note: Chronic Disease Management in Europe, 2008. Back

47   Ernst and Young: Beyond border global biotechnology report, 2011. Back

48   The King's Fund: Spending on health and social care over the next 50 years, 2013. Back

49   Op. cit. Long Term Conditions Compendium of Information. Back

50   See www.gov.uk/government/uploads/system/uploads/attachment_data/file/156133/dh_131856.xls.xls. Back

51   The Oxford Health Alliance: Chronic disease: an economic perspective, 2006. Back

52   Op. cit. Research note: Chronic Disease Management in Europe. Back

53   Her Majesty's Treasury: Speech by the Chancellor of the Exchequer, Rt Hon George Osborne MP, to the Royal Society, November 2012. Back


 
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