Breakthrough_Autumn2006

MYALGIC ENCEPHALOMYELITIS RESEARCH GROUP FOR EDUCATION AND SUPPORT

In June 2006, Dr Vance Spence gave ME Research UK’s presentation at the thirdoral hearing of the Group on Scientific Research into ME (Gibson ParliamentaryInquiry) in the Millbank offices of the House of Commons, London. The Groupwas established by Dr Ian Gibson, Labour MP for Norwich North, who hadbeen a working scientist himself (latterly Dean of Biology at East Anglia) andhead of a research team investigating cancer.

The aim behind the formation of the Gibson Parliamentary Inquiry is toassess the progress of scientific research on ME on behalf of ME patients andresearchers alike. The Group scheduled five oral hearings during the summer of2006, and will publish a report of its findings for public dissemination, tostimulate public debate on the subject and act as a catalyst for increased fundingfor research into the illness.

Our chairman’s presentation was called ME/CFS scientific research: CMOreport and beyond and contained evidence on the lack of progress since the ChiefMedical Officer's report of 2002, specific reasons for the lack of progress(including problems with case definition, the influence of the biopsychosocialmodel of the illness, the undervaluing of biomedical research findings), and a callfor national ring-fencing of funds for biomedical research. A version of his talkcan be read on pages 4 and 5.

The photograph shows (L to R) Dr Neil Abbot (our Director ofOperations), The Countess of Mar, Dr Vance Spence (our Chairman), DorisJones (Environmental Issues Forum) and Dr Jonathan Kerr (St George’sUniversity of London) outside the House of Lords. •

A U G U S T 2 0 0 6

PAGE 2New work recently funded by ME

Research UK

PAGE 3An essay on the muscular and

neurological aspects of ME

PAGES 4 & 5

Our Chairman’s presentation to the

Parliamentary Inquiry

PAGE 6A summary of recent ME/CFS research

from around the world

PAGE 7Research Colloquium in Glasgow 2006

ME Research UK’s new DVD

PAGE 8

How to help ME Research UK

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breakthroughN e w s o f t h e M E r e s e a r c h YO U a r e h e l p i n g t o f u n d

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A U G U S T 2 0 0 6

PA G E 2 MYALGIC ENCEPHALOMYELITIS RESEARCH GROUP FOR EDUCATION AND SUPPORT

B R E A K T H R O U G H W I T H M E R U K

We are currently funding thework of a growing number ofscientists whose research

covers several different areas of interest.Three of the projects for which we haverecently granted funding are brieflydescribed below. •Longitudinal cohort study todetermine the prevalence ofautonomic dysfunction andrelationship with outcome inpatients with ME/CFSDr Julia Newton, School of Clinical MedicalSciences, University of Newcastle, Newcastle

The researchers will explore the roleplayed by the autonomic nervous systemin ME/CFS, using a well-validated batteryof autonomic function tests. The intentionis to examine 100 ME/CFS patientsinitially, and — depending on the findings— to monitor their progress over timeusing further tests.

Non-invasive structural andfunctional neuroimaging in ME/CFSDr Kishore Bhakoo and Professor Basant Puri,MRC Clinical Sciences Centre, ImperialCollege London, London

Given that research studies have indicatedphysiological changes in the brains ofpatients with ME/CFS, this 3-year PhDstudentship will use state-of-the-artmagnetic resonance imaging techniques totry to identify underlying biological organicmechanisms.

The response of interleukin-6 and itsreceptors to a standardised exercisechallengeProfessor Myra Nimmo, Department ofApplied Physiology, University of Strathclyde,Glasgow

This pilot study aims to establish theresponse of IL-6 and its associatedreceptors during a submaximal exercisebout in ME/CFS patients and healthycontrols over a 24-hour period. Thefindings may provide data forming thebasis of a large programme of research onmuscle and nerve function in people withME/CFS.

Recently funded work exploreskey areas in ME/CFS

ME R e s e a r ch UKRe s e a r ch P r o j e c t s

WHAT ISME/CFS?

Myalgic encephalomyelitis/

encephalopathy (ME) is

characterised by a range of

neurological symptoms and

signs, muscle pain with intense

physical or mental exhaustion,

relapses, and specific cognitive

disabilities.

During the 1990s, the term

‘chronic fatigue syndrome’ (CFS)

came into vogue. Since there

was no specific diagnostic test

for ME, and since post-exercise

‘fatigue’ was one of its

prominent symptoms, people

with ME began to be diagnosed

with ‘CFS’. At present, efforts

are being made to revise the

definitions of both ME and CFS,

and meanwhile the term ME/

CFS is used.

ME/CFS affects 120,000 to

240,000 people in the UK, and it

is classified by the World Health

Organisation as a neurological

illness (ICD10: G93.3). Most

people with ME/CFS are unable

to work to full capacity, and

25% are severely disabled, some

house or bed-bound. Little

support is available to their

families and carers. The cause of

the illness is unknown, and no

cure or universally effective

treatment has yet been found.

A report to the Chief Medical

Officer of England in 2002 states

“ME/CFS is a genuine illness and

imposes a substantial burden on

the health of the UK population.

Improvement of health and

social care for people affected

by the condition is an urgent

challenge.”

A U G U S T 2 0 0 6

WHAT ISME Research UK?

ME Research UK is a medical

research charity which

commissions and funds scientific

(biomedical) investigation into

the causes and treatment of ME/

CFS. We also have a mission to

“Energise ME Research”, and

our in-house team identifies

potentially important biomedical

research projects, publishes

scientific papers, produces high-

quality professional reviews and

reports, and organises meetings

and conferences.

Recognising that much of

the existing research into ME

has concentrated on

psychological interventions

designed to “manage” the

illness, ME Research UK

believes that biomedical

research is urgently required

and is what most patients and

carers want to see. For this,

researchers with fresh, novel

ideas have to be recruited and

encouraged to undertake

research in this field. This is the

most difficult task of all, and ME

Research UK sees its role at this

leading edge: to give help to

biomedical scientists for novel

research projects that would

otherwise not be funded, and to

support research groups to the

stage where they can apply to

major funding agencies for

further support based on their

initial data.

With your help — and

building on our close working

relationships with other ME/CFS

organisations around the world

— ME Research UK can be a

force for change, and a source

of real hope for the thousands

of people with this debilitating

illness.

PA G E 3

E N E R G I S I N G M E R E S E A R C H

Epidemics of myalgic encephalo-myelitis (ME) were reviewed byAcheson in 1959, and from 1934 to

1959 there were at least 23 well-documented outbreaks of epidemicproportions of a similar illness.

Many of the findings described byAcheson are very much relevant to ourunderstanding of ME today. The diseasewas initially thought to resemblepoliomyelitis until distinguishing featuresoccurred; no patient developed theparalysis and muscle wasting seen inpoliomyelitis, a disease of the spinal cord.In essence, Acheson described a systemicinfectious illness characterised by markedmuscle weakness (not paralysis); musclepain, tenderness and swelling; and variableinvolvement of the central nervous system.Henderson and Shelokov, in their review in1959, also found that the affected muscleswere tender either diffusely or in focaldiscrete areas, which felt “oedematous,doughy or rubbery in consistence”. Theyalso mentioned the association ofbehavioural disturbances with brain celldisorders such as cranial nerve palsies andhemiparesis. Extensor plantar responsewas an occasional finding in someepidemics, clearly illustrated by MelvinRamsay in his report of a series of sporadiccases in North West London in 1955/6.

Research funded by ME Research UKhas revealed abnormalities in the functionof blood vessels and blood cells. However,these have also been described inepidemics. Infectious material wastransferred from patients to monkeysduring an epidemic in Adelaide, Australia in1949/50. The only abnormalitiesdiscovered at autopsy were minute redspots along the course of the sciaticnerves, found to be localised collections ofinflammatory cells which had alsoinfiltrated the area where the nerve rootscome out of the spinal cord. Again, duringthe North of England epidemic in 1955,

Andrew Wallis described findings in apatient in her 50s who developed thecharacteristic febrile illness, leaving herdebilitated and emotional. During the next15 months she continued to run a lowgrade fever with continued mentaldeterioration before she died. The post-mortem revealed small haemorrhagesaround blood vessels in the cerebralcortex extending into the mid-brain,considered to be the cause of her death.

ME is a muscle/brain disorder whichoccurs as clusters of cases in families, ininstitutions such as hospitals or schools,and in specific areas, but also sporadically.It is an infectious disease with anincubation period of 5 to 8 days. Achesonused the expression “in a greater or lesserdegree” to describe “the symptoms andsigns of damage to the brain and spinalcord” in this disease. This expression canalso be applied to the febrile illness andmuscle involvement. Many patientsrecover, while others have relapses withreactivation of features of the initial illnessand further damage to new areas of thebrain or muscles. In extreme casesdeterioration may lead to death. Afteractivity, the recovery of muscle power isslower than in any other disease. Theassociation between these findings inmuscle and vascular and bloodabnormalities needs to be explored. Forresearch purposes, patients with thesephysical signs should not be coupled withthose whose main illness is chronic fatigueon exertion without these signs. •This is a summary by Dr Neil Abbot of thereview by Dr J Gordon Parish, Patron of MEResearch UK, titled “Reflections on TheClinical Syndrome Variously Called BenignMyalgic Encephalomyelitis, Iceland Diseaseand Epidemic Neuromyasthenia by EDAcheson (American Journal of Medicine1959)”, and available from the Informationsection of our website.

W W W . M E R E S E A R C H . O R G . U K M E R U K @ P K A V S . O R G . U K

ME : A Mu s c l e /B r a inDi s o r d e r

A U G U S T 2 0 0 6



There are a great many sick peopleout there — and some have hadME for many years, myself included.

Yet they have not lost their spirit, and thefact that this Group has been established isa testament not only to the scale of theproblem but also to their feistiness andpersistence in the face of great adversity.

The terms of reference for the Groupinclude an assessment of the progress ofscientific research, specific reasons for thelack of progress, and an examination ofhow can we move forward. I propose toaddress each of these areas in turn.

Progress since the Chief MedicalOfficer’s report of 2002Progress has been patchy and relativelysmall-scale. The MEDLINE database lists783 chronic fatigue syndrome publicationsduring the past 52 months, of which 55were clinical trials, and only 6 of thesewere from the UK. Only 57 (vaguely-defined) experimental studies were fromthe UK, and most of these came from theLondon Medical Schools in which thebiopsychosocial model predominates. Tendiscrete studies emanated from 2privately-funded research groups andanother 6 were one-off studies at variouslocations.

This pattern hardly constitutes anengine room for biomedical investigation ofthe illness, and compares unfavourablywith other illnesses (inthe same 52 monthsthere have been 6,231publications on multiplesclerosis and 48,110 ondiabetes). In fact, ME/CFSresearch is very small-scale, there arecomparatively few“biomedical” studies, andwhile hypotheses aboundthere is often little datato support them. Any

objective observer would conclude thatthe Chief Medical Officer’s report of 2002has had a minimal effect on the drive touncover the causes of ME/CFS.

Specific reasons for lack of progressThere many reasons for the lack ofprogress, but I shall mention briefly 3central issues.

Case definition issuesME, CFS and ME/CFS mean different thingsto different people. This problem coloursall debate on ME, yet like the whiteness ofa wall it is often not recognised as a colourat all. The pie chart below is an attempt todescribe the problem graphically, althoughthe problem may be more or less complexin reality. While the greatest portion of thecircle represents the ‘set’ of patients withchronic fatigue — which might represent 1to 4% of the population — the set ofpatients with CFS (i.e., those with 6-months ‘fatigue’ plus 4 to 8 symptoms) ismuch smaller (0.2 to 0.4% of thepopulation), while those with ME asdescribed in the older scientific literaturemight represent a subset of CFS itself,since post-exercise ‘fatigue’ is a keyelement in their illness. For researchersthe problem is particularly acute sincewhat confidence can they have in thediagnostic discreteness of their patientswhen the diagnosis “CFS” is so broad?

ME/CFS Research: CMOPresentation by Dr Vance Spence to

ON THEWEB

www.meresearch.org.uk

ME Research UK’s website is a

source of news, education and

information on ME/CFS

research and other issues of

interest to biomedical

researchers, healthcare

professionals, people with the

illness and their carers, and the

general public.

The RESEARCH pages contain

summaries and explanations of

projects funded by us, reviews

of the scientific literature,

recently-published ME Research

UK articles, and details of our

funding procedures.

In the INFORMATIONsection, you can find a collection

of literature on ME/CFS and its

consequences, a database of

abstracts of all ME/CFS research

papers from 1956 to 2006, and

ME Research UK’s own

documents discussing and

analysing important issues.

The SUPPORT section

contains information and advice

on accessing social care support

for people with ME/CFS.

The website also keeps you up-

to-date with the latest ME/CFS

research news, and with Friends

of ME Research UK activities.

A U G U S T 2 0 0 6

PA G E 5


Influence of the biopsychosocial modelof ME/CFSIn most illnesses psychosocial techniquesare adjuncts to contemporaneousbiomedical research, whereas in ME/CFSthe biopsychosocial model seems to havedeveloped a life of its own, hoovering upattention and funding, apparently at theexpense of biomedical investigation. As MEResearch UK said in a recent letter to theLancet, “The central point... is that, forpatients with chronic fatigue syndrome (andthere are some 20,000 members ofsupport groups in the UK alone),the biopsychosocial model offersrelatively little, yet it dominates thecanvas in terms of research fundingand exposure in professionaljournals instead of being a smallpart of the overall clinical andscientific picture.” (Abbot NC,Spence VA. Lancet 2006; 367:1574)

Biomedical research findingsundervalued and unsupportedby fundingThe third reason for the lack of progress isthat biomedical research findings into ME/CFS get ignored and undervalued. Yet theyexist, and there is substantial evidencethat, despite the apparent heterogeneity ofthe patient group, biomedical researcherscan uncover a range of interestinganomalies. These include anomalies ofblood flow to the brain, orthostaticintolerance (see photo above from Prof. JMStewart, New York Medical College),increased oxidative stress, raisedinflammatory markers, and activation ofspecific genes.

Furthermore, fascinating one-offresults covering many of the prominentsymptoms of ME/CFS continue to bepublished by research groups worldwide.These include reduction of brain serotonintransporters in relation to pain (Yamamoto


MERUKARTICLES

ME Research UK produces

reviews of scientific research

into ME/CFS, and publishes

general articles on the topic to

raise awareness of the issues.

Recent examples include:

A Scientific ‘Signature’ for

ME/CFS?An essay on current

developments in genetic

research in ME/CFS.

The Muscle in ME: It Isn’t

All Deconditioning!A “research update” overview,

originally published in the

magazine Interaction, in 2005.

New Developments in the

Biology of ME/CFSOur report on the Royal

Society of Edinburgh

Workshop in 2004.

Severely Overlooked

by ScienceAn overview with the 25% ME

Group (with which we have

close links) of research on the

most severely affected ME/CFS

patients.

Advances in the BiomedicalInvestigation of ME/CFS

Describing some recent

developments in biomedical

research, as well as some of the

problems.

Report and Beyondthe Gibson Parliamentary Inquiry

(Burnett et al, 2004) and altered muscleexcitability in response to exercise(Jammes et al, 2005). One particularrecent one-off finding I’d like to highlightconcerns the finding of increased vascularstiffness in ME/CFS patients from my ownunit at the University of Dundee, which fitsin with our provisional hypothesis that atleast some ME/CFS patients might haveincreased cardiovascular risk.

The key point is that breakthroughs inbiomedical research generally follow

funding. Yes, many investigations to datehave been low-level, and in none of theseareas are the findings conclusive as yet.BUT some (or all) of these areas mightwell lead to a breakthrough inunderstanding and treating the illness, andwithout support for biomedical researchwe will never find out.

Since it is left to the smaller charitiesto progress the agenda, we do what wecan. But much more could and should bedone. And the first step is for the largerfunding agencies, including the MedicalResearch Council, to cease beinghypnotised by non-curative “incompleteparadigms” and to begin prioritising basicbiomedical research by ring-fencing centralfunds for basic biomedical research. •This presentation was given at Westminster inJune 2006. The full version is on our website.

A U G U S T 2 0 0 6

SETTINGTHE

AGENDAME Research UK’s publications

and presentations offering

analysis and discussion of public

policy issues.

Unhelpful Counsel?

Our response to the CMO’s

report into the research andtreatment of ME/CFS.

Research into ME/CFS inthe UK: Can the NRRinform future policy?

Our analysis of ME/CFS

research funding sources.

Who Cares?Our submission on care

pathways to the Scottish

Executive’s Short-Life Action

Group on CFS/ME.

Shattered — Life with MEby Lynn Michell, who

collaborated closely with us

during the writing of this book.

Contains a Foreword and

Appendix by ME Research UK.

Cross Party ParliamentaryGroup on ME

Presentation given in 2005 to

the Scottish Parliament by our

Chairman Dr Spence.

Database of ResearchPublications

Contains more than 3,000

research abstracts on ME/CFS,

from 1956 to the present.

Most of these and other

documents can be found on our

website. See the sidebar on

page 4.



Spectroscopic diagnosis in ME/CFSA May 2006 report from Osaka University,Japan presents some astonishing results,for the researchers claim to havedeveloped a way to diagnose ME/CFS usingvisible and near-infrared spectroscopy(Sakudo et al, Biochemical and BiophysicalResearch Communications 2006). Bloodsera from 77 patients and 71 healthydonors were analysed “blind” and theresults subjected to principal componentanalysis (PCA) to examine how sensitivethe test was in discriminating betweenpatients and health controls. The PCAmodel predicted successful discriminationof the masked samples, predicting 54/54(100%) of healthy donors and 42/45(93.3%) of ME/CFS patients.

The authors say that their newapproach deserves further evaluation as apotential strategy for instrumentaldiagnosis of CFS. If true, and replicated byother research groups, the findings wouldbe a great advance in the diagnosticarmoury for ME/CFS, and — intriguingly— they suggest that unknown factor(s) inblood serum are commonly present in allCFS patients.

Causes of death in ME/CFS patientsUsing a memorial list tabulated by theNational CFIDS Foundation in the USA,Prof. Jason and colleagues at DePaulUniversity, Chicago (Health Care forWomen International 2006) have beenexamining causes of death among 144patients for whom sufficient informationwas available.

As expected, there wereapproximately three times more womenthan men (in accord with known genderdifferences), and the three most prevalentcauses of death were heart failure, suicideand cancer (which collectively accountedfor 59.6% of all deaths). Interestingly,complications of ME/CFS were reported tobe the cause of death in 16/144 (11.1%).

The mean age of those who died fromcancer and suicide was 48 and 39 years,respectively, considerably younger thancomparable figures (median values 72 and48 years, respectively) for the generalpopulation. Given research by Peckermanand others highlighting potentialcardiovascular and cardiac problemsamong some patients, it is also of note that20% of the sample was reported to havedied of “heart failure”.

Genes and ME/CFSA recent review in an internationallyrespected journal (Genes and ChronicFatigue: How Strong Is the Evidence?Science 2006) discussed the significance ofthe results of a $2 million study of thehypothalamic-pituitary-adrenal axis genesof 58 CFS patients and other controlsubjects. These results, published in 14scientific papers in one issue ofPharmacogenomics, found differentpatterns of expression of about two dozengenes involved in immune function, cellsignaling and other roles in patients,leading to claims that solid evidence for abiological basis of CFS has been found.

However, the review cites warningsfrom other human geneticists thatconclusions derived from “gene hunts”carried out on such small samples can bemisleading, and that searches of the entiregenome (and not just the HPA axis) areneeded for the valid identification ofdisease markers. •

Recent Research fromAround the World

A MESSAGE

FROM OUR

PATRONS

“ME is a substantial medical and

social problem, yet relatively

little research has been

conducted into its causes and

consequences.

“A recent report to the Chief

Medical Officer said that a

programme of research on all

aspects of the illness is urgently

needed, and that improvement

of health and social care is an

urgent challenge.

“Given the recent sea change in

the public perception of ME, and

the possibility that ME patients

will now be encouraged and

supported rather than derided

and scorned, we hope that ME

Research UK’s scientific and

policy research will lead the way

towards a treatment and cure

for people with ME. Please help

us to make a real difference to

the lives of people with ME.”

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PA G E 7



The first Colloquium on ME/CFSBiomedical Research, sponsored jointly byME Research UK and the Irish ME Trust,took place on Monday 3rd July 2006 atGlasgow Caledonian University (picturedbelow). The event, hosted by Dr LornaPaul, consisted of presentations by keyscientists with a working interest in theillness, and was followed by a workshop onPhysiotherapeutic Aspects of ME/CFS ledby Dr Lorna Paul and Dr Jo Nijs from VrijeUniversiteit Brussel, Belgium.

The event was targeted particularly atscientific and healthcare professionals witha working interest in ME/CFS, and the aimwas to facilitate links between scientistsworking on the biomedical basis of ME/CFS, and to raise awareness of the needfor biomedical investigation.

After a welcome and introduction byProf. Brian Durward (Dean School ofHealth and Social Care, GlasgowCaledonian University), there werescientific presentations from, amongothers, Prof. Jill Belch (Vascular Diseases

Research Unit, University of Dundee), DrJonathan Kerr (Department of Cellular andMolecular Medicine, St George’s Universityof London) and Dr Julia Newton (School ofClinical Medical Sciences, University ofNewcastle).

A professional report consisting of keyoverview summaries of the presentationswill be written and produced by MEResearch UK for subsequent distributionto patients, GPs and healthcareprofessionals. •

The Countess of Mar

Roger Jefcoate, CBE

Colloquium on ME/CFSBiomedical Research

ME Research UK DVDThe short DVD lecture, EnergisingBiomedical Research in ME/CFS, which weproduced earlier in the year has sparkedgreat interest, and to date 4,000 copieshave been distrubuted. The film discussessome issues and challenges involved inresearching the illness, and gives a briefoverview of some of our recent research.Our intention is for this to be the first in aseries of films designed to “energise MEresearch” in its broadest sense.

As Dr Neil Abbot, our Director ofOperations, explains, “We have beenamazed by the response to the film, as ouroriginal intention was simply to make aDVD that could be seen by housebound orbedbound patients. The involvement of thePerth Camcorder Club — a highly

professional group of film-makingenthusiasts who gave their services free —meant that the final product could be ofhigh quality. The 25% ME Group, withwhich we have close working links, hassent one to each of its members, and ourother Group Friends have been sendingcopies to their local GP practice managers,so it’s been an unforeseen excitingrollercoaster!”

And the moral of this extraordinaryresponse? Surely that there is an enormouspent-up demand out there for good qualityinformation on biomedical research in ME/CFS, and a burning desire among patientsand their friends to see fresh, newbiomedical research. Copies are stillavailable; contact us for details. •

A U G U S T 2 0 0 6

To allow us to press ahead with

our mission to Energise ME

Research, please consider

responding to our Standing

Order appeal.

ME Research UK receives no

public money and relies entirely

on donations from ordinary

people. It is vitally important

that all our supporters

understand that we are one of

the very few charities in the

world funding biomedical

research into ME/CFS, and

raising awareness of the issues

in a truly professional manner.

Help us to make the

breakthrough that patients need

and deserve by completing the

standing order form on this

page, or by donating through

the online giving facility via our

website.

Please send this form to:

ME Research UK

The GatewayNorth Methven StreetPerth PH1 5PP, UK

Tel: 01738 451234Email: [email protected]

www.meresearch.org.uk

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Research UK, a/c no. 50419466

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Documents

Breakthrough_Autumn2006