regenerative medicine in the management of neurological conditions · 2015-06-18 · regenerative...

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Regenerative medicine in the management of neurological

conditions

Horizon Scanning Centre

August 2012

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This report presents independent research funded by the National Institute for Health Research (NIHR). The views expressed in this publication are those of the author(s)

and not necessarily those of the NHS, the NIHR or the Department of Health.

The NIHR Horizon Scanning Centre,

University of Birmingham, United Kingdom

[email protected]

www.hsc.nihr.ac.uk

Copyright © University of Birmingham 2012

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Contents Page Number

Summary 4

Introduction and background 5

Clinical need and burden of disease 5

Aims and objectives 6

Methods 6

Results

Identified products 7

Phase III clinical trial – multiple sclerosis 13

Phase II/III clinical trial – spinal cord injury 13

Phase II clinical trials 14

Phase I/II clinical trials 15

Conclusion 15

Appendices

Appendix 1 UK regenerative medicines, organisations and network 17 Appendix 2 Online search sources 18 Appendix 3 Glossary of terms 20

References 21

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Summary

Aim

To identify and investigate the stage of development of emerging regenerative medicine

technologies that potentially may benefit patients with chronic neurological conditions.

Methods

We conducted an initial search to scope the review and identify appropriate contacts and

organisations in the UK. We followed this with a more detailed online search to identify

developments using pre‐determined search terms. Once potential developments had been

found we searched clinical trial databases to gather further information on products closer to

licensing or launch.

Results

Fifteen emerging products or techniques were identified in late clinical trials for a range of

neurological diseases. One is in phase III clinical trials; one in phase II/III trials and thirteen in

phase II. A total of 76 clinical trials were identified in phase I to III trials. The products nearest

to full clinical use are in development for multiple sclerosis and spinal cord injury. Two of the

fifteen trials identified are industry led and one is a joint collaboration between industry and

researchers.

Conclusion

Developments in regenerative medicine for chronic neurological conditions show signs of

promise but it is likely to be several years before any technology is translated into clinical

practice. Multiple sclerosis appears to be the chronic neurological condition that shows most

promise in research with one phase III trial in progress and five phase II trials identified. Stem

cell technology is at the forefront of research in chronic neurological conditions accounting for

over two thirds of research in phase II or III trials. The challenge of demonstrating effectiveness

and safety to use in routine clinical practice still needs to be proven.

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Introduction and background

Regenerative medicine and in particular cellular therapy is a rapidly developing field that is

being investigated as an option for the restoration of function in many disease areas including

neurological disease. Regenerative medicine may have a significant role in the future

treatment of chronic neurological conditions.

There is considerable interest and research of regenerative medicine technologies in chronic

neurological conditions.1 A recent review of neurorestorative clinical trials activity worldwide

identified 106 ongoing or planned clinical trials.2 Approximately three‐quarters of all clinical

trials targeted one of four disease areas: multiple sclerosis, stroke, Parkinson’s disease and

amyotrophic lateral sclerosis. Cell‐based therapy represented two‐thirds of the clinical trials

focus and almost all trials are in phase I or II of development.

Clinical need and burden of disease

A ‘long term neurological condition’ results from disease of, injury or damage to the body’s

nervous system (the brain, spinal cord and/or their peripheral nerve connections) which may

affect the individual and their family for the rest of their lives.3

Long term neurological conditions encompass many different diseases (approximately 130

conditions) and results in very different experiences for people. Conditions may be present at

birth or be acquired later in life. Some conditions appear in childhood, for example muscular

dystrophy, or develop during adult life, including Parkinson’s disease. Some, such as cerebral

palsy and hydrocephalus may be associated with varying degrees of learning disability. The

prognosis for different conditions also varies widely. The average time between diagnosis and

death for someone with motor neurone disease is 14 months, while someone with multiple

sclerosis may live with the condition for decades.

Neurological conditions affect people of all ages, although the prevalence of neurological

conditions increases with age. Over the next two decades it is predicted that the number of

people with neurological conditions will increase significantly due to factors including

improved survival rates, improved general health care, increased longevity and improved

diagnostic techniques.3

A review undertaken in the United Kingdom (UK) estimated that there are in excess of 10 million people living with a neurological condition that has a significant impact on their lives.4 Over 1 million people (approximately 1 in 60 people of the UK populationa) are disabled by their neurological condition.2 Typically disability means people may need help with some daily

a Applying Office for National Statistics (ONS) mid‐2010 UK population estimate of 62.3 million

http://www.ons.gov.uk/ons/rel/pop‐estimate/population‐estimates‐for‐uk‐‐england‐and‐wales‐‐scotland‐and‐

northern‐ireland/mid‐2010‐population‐estimates/index.html

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tasks and are likely to be out of full time employment. This figure includes most people living with cerebral palsy, those who have recently had a brain injury or illness, those who have had a stroke, some people living with motor neurone disease (MND), multiple sclerosis (MS), Parkinson’s disease and forms of dementia.4 It also includes some of those with epilepsy or migraine. Annually, an estimated 1% of the UK population are newly diagnosed with a neurological condition equating to 600,000 people.4 In primary care, 17% of GP consultations are for neurological conditions, and in secondary care, 10% of accident and emergency visits and 19% of hospital admissions are for neurological conditions.4

The NHS spend on neurological conditions has increased by 38% in real terms, from £2.1 billion

in 2006‐07 to £2.9 billion in 2009‐10. Spending on social services for people with neurological

conditions has remained at an estimated £2.4 billion for the period 2005‐06 to 2009‐10.5

Currently there are no curative therapies or interventions for the majority, if not all, long term

neurological conditions and the aim of health and social care is to maximise quality of life for

people.2 The majority of treatments currently available help to reduce symptoms of disease

rather than affect progression. The hope is that regenerative medicine techniques and

products may restore the function of diseased or damaged tissues or organs through a variety

of approaches.6

Aims and objectives

The aim of this review is to identify and to investigate the stage of development of emerging

regenerative medicine technologies that potentially may benefit patients with chronic

neurological conditions.

Methods

We undertook an initial search of online sources to scope the review.

Detailed online search

We conducted an online search to find developments using combinations of pre‐determined

search terms including: neurological, nervous system, stem cells, gene therapy, tissue

engineering, biomedical technology and transplants.

Sources used (see appendix 2) included:

Medline, Embase and the Cochrane research database

Regulatory authorities

UK research councils

EU framework programme research consortia

Global trial registries

UK regenerative medicine organisations and networks (see appendix 1)

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Once we had identified potential developments we searched clinical trial databases to identify

developers and specific technologies that are in clinical trials closer to licensing and launch.

We initially searched for any cell therapy, tissue engineering and regenerative technique

products being developed for any neurological indications in any clinical trial phase. We then

excluded any that were in, or had reported results from proof of concept or phase I trials, but

had no indication or evidence of ongoing phase II trials. Trials that were listed as phase I/II

were excluded if they were essentially proof of concept trials. For technologies in phase II or III

trials additional information about complete or ongoing trials was collected. Stroke is classified

as a long term neurological condition but is excluded from this review due to its inclusion in the

published cardiovascular disease review.

Results

Identified Products

We identified 76 relevant clinical trials of regenerative medicine techniques and products

across 14 neurological conditions (table 1). Two principal therapy approaches were identified;

cellular therapy and gene therapy. Cellular therapy was the research approach used in 68 of

the clinical trials. Eighty per cent of the trials were in phase I or II, 17% in phase II, and one

each in phase II/III and phase III stages.

Multiple sclerosis and spinal cord injury were the two most researched conditions with 20 and

19 clinical trials identified respectively. Parkinson’s disease and amyotrophic lateral sclerosis

both had nine clinical trials identified. The four most researched conditions totalled 57 (75%) of

the clinical trials identified. The remaining nine chronic neurological conditions had fewer than

five clinical trials identified per condition.

Table 2 details the approach or intervention under investigation, indication, sponsors and

collaborators, and any relevant trial information for those in phase II and III clinical trials.

Stem cell therapy was almost exclusively the cellular therapy of choice, with adult stem cells

being used predominantly. Hematopoietic or mesenchymal stem cells were used in trials with

sources including bone marrow, peripheral blood and umbilical cord. Autologous and

allogeneic stem cells were investigated, with a similar number of trials under investigation at

phase II. The procedures of extracting and inserting the stem cells in to humans varied, as did

the use of immunotherapy. Six of the eight clinical trials utilising gene therapy were focused on

Parkinson’s disease.

Research was undertaken or involved collaboration with industry in twenty one clinical trials

(27%). Three of the phase II trials involved industry, the remaining eighteen trials were all at an

earlier phase.

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Table 1: Summary of clinical trials identified for chronic neurological conditions by condition, therapy type and phase.

Condition Therapy Clinical trial phase

Cellular therapy Gene therapy I I/II II II/III III Total

Alzheimer's disease 2 2 2 1 1 0 0 4

Amyotrophic lateral sclerosis† 9 0 4 4 1 0 0 9

Cerebral palsy 4 0 1 2 1 0 0 4

Encephalopathy 1 0 0 1 0 0 0 1

Hereditary ataxia 1 0 0 1 0 0 0 1

Hereditary cerebral ataxia 1 0 1 0 0 0 0 1

Huntington's disease 1 0 0 0 1 0 0 1

Multiple sclerosis 20 0 5 9 5 0 1 20

Neurological 1 0 1 0 0 0 0 1

Parkinson’s disease 3 6 2 6 1 0 0 9

Myasthenia gravis 1 0 1 0 0 0 0 1

Spinal cord injury 19 0 7 8 3 1 0 19

Epilepsy 1 0 1 0 0 0 0 1

Brain injury 4 0 1 3 0 0 0 4

TOTAL 68 8 26 35 13 1 1 76

† The most common form of Motor neurone disease (also known as Lou Gehrig’s disease).

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Table 2: Products in Phase II and/or III clinical development

Indication Approach/Intervention Sponsor/Collaborator Phase Trial information Route/method of delivery

Multiple sclerosis

Autologous unmanipulated peripheral blood stem cell therapy.

Northwestern University, USA

III Hematopoietic stem cell therapy for patients with inflammatory multiple sclerosis failing interferon: a randomized study (NCT00273364).7 Estimated enrolment 110 patients, estimated primary completion December 2012.

Not stated

Spinal cord injury

Bone marrow derived adult stem cells (unknown if autologous or allogeneic)

Bansal Foundation, India

II/III An open label, randomised, multicentre, prospective, clinical study to determine the safety and therapeutic effectiveness of bone marrow derived adult stem cells via multiple routes of administration in the treatment of patients with complete spinal cord injury (CTRI/2010/091/001469).8 Estimated enrolment 100 patients, estimated duration of trial 2 years from commencement in February 2011.

Intrathecally below the site of lesion, intravenously or directly at the site of lesion

Alzheimer’s disease

Gene therapy: CERE‐110: adeno‐associated virus delivery of nerve growth factor

Ceregene, USA II A double‐blind, placebo‐controlled (sham surgery), randomized, multicenter study evaluating CERE‐110 gene delivery in subjects with mild to moderate Alzheimer's disease (NCT00876863).9 Estimated enrolment 50 patients, estimated primary completion December 2013.

Injection into brain during surgery

Amyotrophic lateral sclerosis

Allogeneic umbilical cord mesenchymal stem cells

General hospital of Chinese armed police forces

II The clinical study on the use of umbilical cord mesenchymal stem cells in amyotrophic lateral sclerosis (NCT01494480).10 Estimated enrolment 30 patients, estimated primary completion January 2013.

Intrathecal injection ‐ lumbar puncture

Cerebral palsy

Allogeneic umbilical cord blood

Bundang CHA Hospital, Republic of Korea

II FLT(3'‐Deoxy‐3'‐[F‐18]Fluorothymidine)‐PET activity change after allogeneic umbilical cord blood cell therapy in cerebral palsy (NCT01486732).11 Estimated enrolment 40 patients, estimated primary completion April 2012. Study suspended.

Infusion intravenously or intraarterially under non‐myeloablative immunosuppression

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Huntington’s disease

Intracerebral graft of homologous foetal neurons

Assistance Publique ‐Hôpitaux de Paris

II Multicentric intracerebral grafting in early Huntington's disease(NCT00190450).12 Estimated enrolment 60 patients, estimated primary completion May 2013.

Intracerebral graft

Multiple sclerosis

Autologous mesenchymal stem cells

Albert Saiz, hospital clinic of Barcelona

II Autologous mesenchymal stem cell transplantation in a randomized, double‐blind, crossover with placebo phase II study (NCT01228266).13 Estimated enrolment 16 patients, estimated primary completion June 2012.

Single infusion

Multiple sclerosis

Autologous CD34+ hematopoietic stem cell transplant

National institute of allergy and infectious diseases (NIAID), USA

II High‐dose immunosuppressive therapy (HDIT) using carmustine, etoposide, cytarabine, and melphalan (BEAM) and thymoglobulin, and autologous CD34+ hematopoietic stem cell transplant (HCT) for poor prognosis multiple sclerosis (NCT00288626).14 Estimated enrolment 25 patients, estimated primary completion September 2014.

Not stated

Multiple sclerosis

Autologous hematopoietic stem cell transplant

National institute of neurological disorders and stroke (NINDS), USA

II Immunological mechanisms of immune ablation and autologous hematopoietic stem cell transplantation in secondary progressive multiple sclerosis (NCT00342134).15 Estimated enrolment 34 patients, estimated primary completion May 2011. Completed.

Not stated

Multiple sclerosis

Autologous CD34 selected hematopoietic stem cell transplant

Ottawa hospital research institute, Canada

II Intensive immunoablative therapy and immunological reconstitution: a potential curative therapy for patients with a predicted poor prognosis (NCT01099930).16 Estimated enrolment 24 patients, estimated primary completion December 2012.

Not stated

Multiple sclerosis

Hematopoietic CD34 stem cell transplant

Baylor college of medicine, USA

II Intensive immunosuppression followed by rescue with CD34 elected, T cell depleted, leukopheresis products (NCT00040482).17 Estimated enrolment 10 patients. Completion August 2005. No recent trial activity and no results identified.

Intravenous via central line in to neck or chest

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Parkinson’s disease

Gene therapy: AAV‐GAD Neurologix, Inc., USA II Safety and efficacy study evaluating glutamic acid decarboxylase gene transfer to subthalamic nuclei in advanced Parkinson's disease (NCT00643890).18 Estimated enrolment 44 patients, estimated primary completion December 2010. Terminated due to financial reasons.

Infusion into the subthalamic nucleus

Spinal cord injury

Mesenchymal stem cells derived from umbilical cord transplant


II Efficacy difference between rehabilitation therapy and umbilical cord derived mesenchymal stem cells transplantation in patients with acute or chronic spinal cord injury in China (NCT01393977).19 Estimated enrolment 60 patients, estimated primary completion May 2012.

Lumbar puncture directly into subarachnoid

Spinal cord injury

Autologous incubated macrophages (Procord)

Proneuron Biotechnologies, USA

II Multicenter, randomized‐controlled study to evaluate the safety and efficacy of autologous incubated macrophages for patients with complete spinal cord injuries (NCT00073853).20 Estimated enrolment 61 patients. Commenced September 2003. Study has been suspended.

Injection into spinal cord

Spinal cord injury

Umbilical cord mesenchymal stem cell transplantation


II The safety and efficacy of umbilical cord mesenchymal stem cell transplantation (ChiCTR‐ONC‐12002005).21 Estimated enrolment 20 patients, estimated primary completion December 2013.

Femoral artery interventional procedure

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Phase III clinical trial – multiple sclerosis

One clinical trial (NCT00273364) in the United States researching autologous unmanipulated

peripheral blood hematopoietic stem cell therapy for multiple sclerosis (n=110) was

identified at phase III. The trial aims to demonstrate the efficacy of stem cell transplant with

a conditioning therapy of cyclophosphamide and anti‐thymocyte globulin (rATG) compared

to Food and Drug Administration (FDA) approved standard of care (interferon, copaxone or

mitoxantrone) for patients with inflammatory (relapsing) multiple sclerosis failing interferon

therapy. Patients will be followed up every six months for five years. Researchers hope that

stem cell therapy may provide a mechanism of preventing progressive disease disability,

which current immune therapy is not proven to achieve.

A previous phase I/II clinical trial (n=21) investigating the use of autologous non‐

myeolablative haemopoeitic stem cell transplantation in relapsing‐remitting multiple

sclerosis suggested that for patients with relapsing‐remitting multiple sclerosis, neurological

deficits may be reversed.22 The authors state that after 37 months (range 24‐48 months) all

patients were free from progression and 16 were free from relapses.

Clinical investigation of autologous haemopoeitic stem cell transplantation as therapy for

multiple sclerosis has been ongoing for over a decade.23 Due to its risk profile,

immunodepletion followed by autologous haemopoeitic stem cells has been restricted to

patients with highly active, rapidly deteriorating, treatment refractory primary or secondary

progressive forms of multiple sclerosis.24 The safety and efficacy outcomes published to‐

date cannot therefore be transferred to other forms of multiple sclerosis. The question of

which conditioning regimen offers the optimal risk/benefit ratio remains unanswered.24 A

recent systematic review concluded that patients with secondary progressive multiple

sclerosis refractory to conventional medical treatment have longer progression‐free survival

(up to 3 years post treatment) following autologous stem cell transplant with intermediate‐

intensity conditioning regimens than with high‐intensity conditioning regimens.25

A phase III multicentre randomised controlled trial is currently in development to establish

the role of haemopoeitic stem cell transplantation for the treatment of severe, active forms

of multiple sclerosis.26 ‡

Phase II/III clinical trial – spinal cord injury

There is a phase II/III clinical trial (CTRI/2010/091/001469, n=100) ongoing for people with a

complete spinal cord injury. Bone marrow derived adult stem cells are to be administered

intrathecally below the site of lesion, intravenously or directly at the lesion site. Researchers

aim to demonstrate that the procedures are safe and therapeutically effective. Neurological

‡ It is unclear whether this trial is the same trial as NCT00273364 as reported above.

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and urinary bladder functions will be clinically assessed to determine efficacy. The study

requires the injury to have occurred from one month up to a year before inclusion.

A recent systematic review highlighted the paucity of studies carried out in more clinically

relevant models of spinal cord injury, with current clinical trials justified primarily on the

basis of pre‐clinical studies conducted predominantly in thoracic models to determine safety

and feasibility of the cellular interventions.27

Phase II clinical trials

Thirteen phase II clinical trials were identified covering seven chronic neurological

conditions. Cellular therapy accounted for 11 of the trials and stem cells used as the

intervention in nine. Two other cellular based approaches were identified.

A clinical trial in people with early Huntington’s disease in France is substituting

degenerated striatal neurons using a bilateral intracerebral graft of homologous foetal

neurons. The clinical effect of this approach will be assessed using the Unified Huntington

Disease Rating Scale (UHDRS). The other cellular approach was investigating the benefits of

autologous incubated macrophages (Procord) injected into the spinal cord for complete

spinal cord injury. The theory behind this approach was to circumnavigate the biochemical

mechanism known as immune privilege and support the regeneration of axons through the

injury site and enable the recovery of neurological function. However, this study has been

suspended with the company stating that it is not due to any clinical or safety concerns. A

phase I open label nonrandomised trial had previously been conducted to assess the safety

and tolerability of incubated autologous macrophages administered to patients with spinal

cord injury.28 The authors concluded the therapy to be well tolerated with further

evaluation warranted.

Two trials were investigating the use of gene therapy, one for Alzheimer’s disease and the

other for Parkinson’s disease (terminated due to funding). The Alzheimer’s disease trial

(mild to moderate disease) uses CERE‐110, an experimental technology that is designed to

help nerve cells in the brain function better. CERE‐110 uses an adeno‐associated virus to

transfer a gene that makes nerve growth factor (NGF), a protein that may make nerve cells

in the brain healthier and protect them from dying. CERE‐110 is injected into the brain

during a surgical procedure. The Alzheimer's disease assessment scale ‐ cognitive subscale

(ADAS‐Cog) will be used to assess the outcome of the trial. This follows a phase I trial

(NCT00087789) that indicated CERE 110 gene therapy delivery was safe in six patients with

mild‐to‐moderate Alzheimer’s disease and warranted further investigation. The results of

the Parkinson’s disease phase II trial have been published with the authors suggesting that

the efficacy and safety of bilateral infusion of AAV2‐GAD shows promise for gene therapy.29

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The phase I open‐label trial of AAV‐GAD had been interpreted as showing gene therapy of

the subthalamic nucleus to be safe and well tolerated.30

Of the thirteen phase II trials identified, two have been suspended and one terminated due

to financial reasons, and a fourth trial was completed in 2005 but has not had any results

published.

Phase I/II clinical trials

Cellular therapy, particularly stem cell transplantation, dominates the approaches being

trialled in the phase I trials. Information available infers that stem cells in trials are often

used unchanged but may have been expanded/enriched/activated prior to being

administered.

There is a variation in the approach to using immunosuppression (conditioning regimes)

between the trials. Researchers are looking into the theory that no or partial

immunosuppression may be as effective as immunoablation due to the phenomenon known

as graft versus tumour effect. The additional benefit if successful is that it may be better

tolerated and potentially available to a wider group of patients.

An ongoing trial is the first to investigate the use in humans of fetal‐derived neural stem

cells transplanted into the spinal cord in the treatment of amyotrophic lateral sclerosis. This

trial design was one of escalating risk, where each group of patients is progressively less

impaired by the disease. Another trial is investigating intramedullary transplantation of

human central nervous system stem cells in people with thoracic (T2‐T11) spinal cord injury.

A phase I trial by Geron, the first to use differentiated human embryonic stem cells for

spinal cord injury has been withdrawn for commercial reasons.

Conclusion

Chronic neurological conditions cover a wide and diverse range of diseases, including those

that are rare and common. People living with these diseases often have poor prognosis,

with degeneration and/or loss in body function over the short to long term. For most

conditions current treatment, if available, may at best reduce symptoms rather than target

the cause of disease. It is not surprising that there is great interest in the potential of

regenerative medicine for these conditions.

The majority of research identified by this review is unsurprisingly focused on the more

common diseases, including multiple sclerosis and spinal cord injury. This finding agrees

with a previous review of neurorestorative clinical trials activity.5 The majority of clinical

trials focus on cellular therapy and are in phase I or II of development. Where results are

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available investigators often suggest that safety and efficacy has been demonstrated and

further trials are warranted. However, the trials are usually open‐label, non‐randomised

with small patient numbers. Until larger comparative studies are undertaken and results

published, questions around the use and place of cellular therapy in neurological conditions

remain unanswered.

There are numerous clinical trials for neurological conditions conducted with adult stem

cells, with only one trial investigating embryonic stem cells, which has now been withdrawn.

The trial for Huntington’s disease uses foetal neurons, however there is debate as to

whether this is truly classed as stem cell therapy. The focus for gene therapy research in

neurological conditions appears to be on Parkinson’s disease, however the most advanced

trial at phase II has been terminated due to funding.

A number of completed phase I and phase I/II trials indicate that stem cell therapy may be

safe and tolerated in people with neurological conditions. However, at present there are

many approaches being investigated across different diseases which indicates that a

commonly agreed best approach has not yet been identified. The fact that the majority of

trials for neurological conditions are still at an early phase assessing safety and efficacy

suggests that the reality of using such approaches in everyday healthcare is many years

away.

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Appendix 1: UK regenerative medicines organisations and networks

UniverCell Market https://www.univercellmarket.com/

Source of up‐to‐date information for the global stem cell and regenerative medicine community.

Renger8 http://www.regener8.ac.uk/home.html

The translational centre for regenerative medicine that brings together the work of UK scientists

with UK and international industry to advance the development of tools and technologies to

accelerate therapies through to clinic.

East of England Stem Cell Network (EESCN)

http://www.cambridgenetwork.co.uk/directory/orgprofile/default.aspx?objid=67752

EESCN is the UK's largest regional stem cell network, representing the interests of world class

researchers, clinicians and businesses involved in regenerative medicine and stem cell science, as

well as providing opportunities for public engagement.

London Regenerative Medicine Network (LRMN) http://www.lrmn.com/

The London Regenerative Medicine Network is the world's largest cell therapy and regenerative

medicine network with in excess of 5,500 members representing all the stakeholder groups

including: the general public, patients, patient advocates, students, scientists, engineers, clinicians,

charities, government organisations and business people.

Merica Stem Cell Alliance (previously Northeast England Stem Cell Institute)

http://www.msca.ls.manchester.ac.uk/

Alliance’s collaborators have established notable regional Centres of Excellence, lead major science‐

driven companies, and collectively maintain a skill set which supports the translation of basic

research to innovative therapies.

Scottish Stem Cell Network (SSCN) http://www.sscn.co.uk/

The aim of the network is to bring together scientists and clinicians in order to improve the rate at

which laboratory research translates into therapeutic benefits for patients. The SSCN works with the

entire stem cell community in Scotland, including academic institutions, clinical and industry‐based

research groups, as well as suppliers in the field.

The Social Science Stem Cell Initiative http://www.york.ac.uk/res/sci/introduction.htm

The ESRC Social Science Stem Cell Initiative was set up in 2005 with the broad aim of supporting a

range of activities to build research capacity and raise awareness in the UK social science community

regarding the emerging field of stem cell science.

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Appendix 2: Online search sources

Regulatory authorities Web Address European Medicines Agency (EMEA)

http://www.ema.europa.eu/ema/index.jsp?curl=/pages/home/Home_Page.jsp&jsenabled=true

Human Fertilisation and Embryology Authority (HFEA) http://www.hfea.gov.uk/

Human Tissue Authority (HTA) http://www.hta.gov.uk/

Medicines and Healthcare Products Regulatory Agency (MHRA)

http://www.mhra.gov.uk/index.htm

US Food and Drug Administration (FDA) http://www.fda.gov/

UK government departments Web Address Department of Health (DH) http://www.dh.gov.uk/en/index.htm

Department for Business, Innovation and Skills (BIS) http://www.bis.gov.uk/

UK research councils Web Address Biotechnology and Biological Sciences Research Council (BBSRC)

http://www.bbsrc.ac.uk/

Economic and Social Research Council (ESRC) http://www.esrc.ac.uk/

Engineering and Physical Sciences Research Council(EPSRC)

http://www.epsrc.ac.uk/pages/default.aspx

Medical Research Council (MRC) http://www.mrc.ac.uk/index.htm

Science and Technology Facilities Council (STFC) http://www.stfc.ac.uk/

Technology Strategy Board (TSB) http://www.innovateuk.org/

Learned Societies Web Address Academy of Medical Sciences (AMS) http://www.acmedsci.ac.uk/

British Pharmacological Society (BPS) http://www.abpi.org.uk/Pages/default.aspx

British Society for Cell Biology (BSCB) http://www.bscb.org/

British Society for Developmental Biology (BSDB) http://www.bms.ed.ac.uk/services/webspace/bsdb/welcome.htm

International Society for Cellular Therapy (ISCT) http://www.celltherapysociety.org/

International Society for Stem Cell Research (ISSCR) http://www.isscr.org//AM/Template.cfm?Section=Home

International Society of Differentiation (ISD) http://www.isdifferentiation.org/

Royal Academy of Engineering http://www.raeng.org.uk/

Royal College of Surgeons of England (RCS) http://www.rcseng.ac.uk/

Royal Pharmaceutical Society of Great Britain (RPSGB) http://www.rpharms.com/home/home.asp

Royal Society http://royalsociety.org/

Tissue and Cell Engineering Society (TCES) http://www.tces.org/

Tissue Engineering International & Regenerative Medicine Society (TERMIS)

http://www.termis.org/

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EU Framework Programme Research Consortia

Web address

ES TOOLS http://www.estools.eu/

EuroStemCell http://www.eurostemcell.org/

Miscellaneous Web address Association of the British Pharmaceutical Industry (ABPI)

http://www.abpi.org.uk/Pages/default.aspx

BioIndustry Association (BIA) http://www.bioindustry.org/

California Institute for Regenerative Medicine (CIRM)

http://www.cirm.ca.gov/

Centre of the Cell http://www.centreofthecell.org/

Stem Cells for Safer Medicines Ltd http://www.sc4sm.org/

Stem Cell Patents http://www.stemcellpatents.com/

UK Intellectual Property Office (UKIPO) http://www.ipo.gov.uk/

Free Patents Online Search Engine http://www.freepatentsonline.com/

UK charitable organisations Web address Action Duchenne http://www.actionduchenne.org/

Alzheimer’s Research Trust http://www.actionduchenne.org/

Alzheimer’s Society http://www.alzheimers.org.uk/site/index.php

Association of Medical Research Charities

http://www.amrc.org.uk/homepage/

The Cure Parkinson’s Trust http://www.cureparkinsons.org.uk/

Motor Neurone Disease Association (MNDA)

http://www.mndassociation.org/

Multiple Sclerosis Society http://www.mssociety.org.uk/

Muscular Dystrophy Campaign http://www.muscular‐dystrophy.org/

Parkinson’s UK http://www.parkinsons.org.uk/

UK Stem Cell Foundation (UKSCF) http://www.ukscf.org/

Research Publications and Trials in progress

Web address

ClinicalTrials.gov http://www.clinicaltrials.gov/

WHO International Clinical Trials Registry

http://www.who.int/trialsearch/Default.aspx

EU Clinical Trials Register https://www.clinicaltrialsregister.eu

Current Controlled Trials http://www.controlled‐trials.com/mrct/

UKCRN Portfolio Database http://public.ukcrn.org.uk/search/

ClinicalStudyResults.org http://www.clinicalstudyresults.org/home/

The Cochrane Library (Clinical trials) http://www.cochrane.org/

PubMed, Medline & Medline in Progress, & EMBASE

http://www.elibrary.bham.ac.uk/

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Appendix 3: Glossary of terms

Allogeneic: stem cells from a genetically similar, but not identical donor.

Autologous: .stem cells originating from the recipient rather than from a donor Embryonic stem cells: pluripotent stem cells derived from the inner cell mass of the blastocyst, an early‐stage embryo.

Mesenchymal stem cells: multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts (bone cells), chondrocytes (cartilage cells) and adipocytes (fat cells).

Pluripotent stem cells: can give rise to any fetal or adult cell type. However, alone they cannot develop into a fetal or adult animal because they lack the potential to contribute to extra embryonic tissue, such as the placenta.

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