e University
[The text below can be read in association with its extensive web links at =
http://www.meresearch.org.uk/mrcaward.html]
The award by the MRC of almost =A31 million to Professor Julia Newton, Dr W=
an Ng and colleagues (Newcastle Biomedicine, Newcastle University, UK) for =
two biomedical projects is a great boost for research into ME/CFS in the UK=
. The initial call for applications "Understanding the Mechanisms of CFS/ME=
" http://www.mrc.ac.uk/Fundingopportunities/Calls/MechanismsofCFSME/MRC0077=
15 was issued by the MRC in February 2011, with a submission deadline in Ju=
ne 2011. In total, the MRC has made 5 discrete grant awards under this call=
, at a cost of approximately =A31.65 million.
As Prof Newton says, "I am delighted at this outcome, which arrives after m=
any years of hard work for my colleagues and myself. I'd like to particular=
ly thank the charity ME Research UK. The charity provided the pilot/seedcor=
n funding for 4 distinct projects from 2006-2011, which have allowed us to =
accumulate the data on which these successful applications to the MRC were =
based [see Note 1 below]. In addition, ME Research UK has supported our res=
earch programme in a variety of ways, not least by providing formal support=
letters for our grant applications to the MRC. The success of these applic=
ations shows what can be achieved by biomedical researchers working closely=
with medical research charities in a supportive and collaborative way".
Dr Neil Abbot, on behalf of ME Research UK, said [see Note 2 below], "The a=
llocation of these monies under a "pathophysiology" call, culminating in th=
e award of grants for research that is overwhelmingly "biomedical" rather t=
han "psychosocial" in nature, is a significant achievement for which Prof S=
tephen Holgate, the ME/CFS charities and the MRC itself deserve congratulat=
ions. The task now is to ensure that Class I funding continues to be availa=
ble, year-on-year, for biomedical research into a disease that has been ove=
rlooked for far too long."
The MRC had invited "proposals for high-quality, internationally competitiv=
e research partnerships addressing CFS/ME...focusing on one or more of the =
following areas:....Autonomic dysfunction; Cognitive symptoms; Fatigue; Imm=
une dysregulation; Pain; and Sleep disorders". The awards given to Professo=
r Newton, Dr Wan Ng and colleagues were allocated under MRC-identified focu=
s areas of "Autonomic dysfunction" and "Immune dysregulation", and the fund=
ed projects aim to explore in greater depth:
1. Autonomic dysfunction, a phenomenon observed in the majority of patients=
investigated in Newcastle [see Note 1 below]. The researchers plan a detai=
led exploration of its pathogenesis, including its relationship with the ne=
urocognitive impairments seen in patients [see Note 3 below].
2. Biological fingerprints of fatigue using whole blood gene expression pro=
filing. Using primary Sjogren's syndrome (an autoimmune condition with seve=
ral clinical features similar to ME/CFS) as a disease model, the researcher=
s will undertake a comprehensive analysis of the immune system to identify =
biological fingerprints. Subsequently, they will explore whether these biom=
arkers are present in ME/CFS patients, and whether they have role in improv=
ing diagnosis and treatment
_______________________________________________________
Notes
Note 1. Scientific progression at the University of Newcastle
The research headed by Prof Julia Newton http://www.ncl.ac.uk/biomedicine/r=
esearch/groups/profile/julia.newton and Prof David Jones of the School of C=
linical Medical Sciences, University of Newcastle (Newcastle Biomedicine) i=
s one of the very few research "programs" anywhere in the world on ME/CFS =
- and a rare example of a consistent, directed, problem-solving approach t=
o tackling the illness.
Since 2006, the group has received 3 separate grants from ME Research UK to=
look at:
a) the autonomic nervous system (2006) http://www.meresearch.org.uk/researc=
h/projects/potsincfs.html;
b) muscle bioenergetics (2009) http://www.meresearch.org.uk/research/projec=
ts/bioenergetics.html;
c) systems analysis (2010) http://www.meresearch.org.uk/research/projects/s=
ystems.html.
d) In addition, the researchers received a large grant (2007) from ME Resea=
rch UK, the John Richardson Research Group, and the Irish ME Trust for "Aut=
onomic nervous system dysfunction: a two-year investigation" http://www.mer=
esearch.org.uk/research/projects/autonomic2.html to examine muscle, liver a=
nd heart function in a large patient cohort.
These investigations have resulted in a series of novel, incremental, scien=
tific papers showing that, compared with healthy people, ME/CFS patients ca=
n have:
(i) Dysfunction of the autonomic nervous system (three-quarters of patients=
) (QJM. 2007 Aug;100(8):519-26)
(ii) Fatigue and functional impairment that is directly related to the burd=
en of autonomic nervous system symptoms (QJM. 2010 Aug;103(8):589-95)
(iii) An abnormal heart rate response to standing (QJM. 2008 Dec;101(12):96=
1-5)
(iv) Lower blood pressure, and abnormal blood pressure regulation (Psychoso=
m Med. 2009 Apr;71(3):361-5)
(v) Impaired cardiovascular responses to standing (Eur J Clin Invest. 2010 =
Jul;40(7):608-15)
(vi) Substantially slower recovery from standarised exercise of the skeleta=
l muscles (Eur J Clin Invest 2011 June. Epub ahead of print; and J Intern M=
ed. 2010 Apr;267(4):394-401)
(vii) Impaired cardiac function, including markedly reduced cardiac mass an=
d blood pool volumes (J Intern Med. 2011 Jul 27. Epub ahead of print)
(viii) Alternative diagnoses to the diagnosis of ME/CFS originally given by=
their GPs, with around 40% of patients being diagnosed with other chronic =
diseases, such as primary sleep disorders, and psychological or cardiovascu=
lar illnesses (J R Coll Physicians Edinb. 2010 Dec;40(4):304-7)
Such a progression is the norm for scientific investigation - whether towar=
ds positive findings or away from negative ones. In fact, in most chronic d=
iseases, real breakthroughs come only after years of painstaking work by sp=
ecialist groups of researchers across the world - after a "critical mass" o=
f investigators has produced a "critical mass" of biomedical data. For the =
scientific enigma(s) of ME/CFS to be solved, the disease must become the ma=
in focus of a wide range of investigative programs across the globe.
=AD_______________________________________________________
Note 2. ME Research UK comment: MRC and funding for ME/CFS research
The issue of MRC funding for ME/CFS research has been a "hot potato" for ma=
ny years. So hot, in fact, that the fractiousness of the debate has been a =
marvel to outside observers whether scientists, healthcare professionals or=
journalists.
In brief, ME/CFS patients, support groups and charities have opposed the al=
location of MRC funds for the investigation of "biopsychosocial models" at =
the expense of "biomedical" investigations designed to find the causes of t=
he underlying physical illness. Indeed, in an analysis entitled "The Medica=
l Research Council: a case to answer?" http://www.meresearch.org.uk/informa=
tion/publications/casetoanswer.html, ME Research UK showed that approximate=
ly 91% of the total grant-spend on ME/CFS by the MRC from 2003-2008 (at lea=
st =A33,180,900 at the time) had gone on trials of non-specific management =
and coping strategies. As this essay said, "In an ideal world in which =A31=
00 million had been invested over five years in ME/CFS research, a 3% spend=
on assessing the usefulness of various coping strategies, such as CBT, rel=
axation or meditation, might have been acceptable. The point at issue is th=
at most of the MRC's inadequate grant-spend has gone on this aspect at the =
expense of truly biomedical research, the reverse of the situation in other=
illnesses such as multiple sclerosis or rheumatoid arthritis."
Since 2008, however, there has been a much greater level of engagement betw=
een the MRC and ME/CFS charities at a professional level. First, the arriva=
l into the field of Prof Stephen Holgate (MRC Clinical Professor of Immunop=
harmacology at the University of Southampton School of Medicine), who had p=
revious experience of organising a successful research collaborative in res=
piratory illnesses, brought new momentum, not least through his chairmanshi=
p of a novel "MRC CFS/ME Expert Group" to consider how new high-quality res=
earch into CFS/ME might be encouraged. Then, a Research Workshop was held i=
n November 2009, at which established researchers and scientific representa=
tives of charities - including Dr Vance Spence and Dr Neil Abbot of ME Rese=
arch UK - met to set research priority areas. This was followed by the form=
ation of an "MRC CFS/ME Research Prioritisation" group to prioritise the re=
search topics raised at the Research Workshop as a prelude to action. The c=
ulmination of this process was the "Call for proposals: Understanding the M=
echanisms of CFS/ME" in February 2011, under which Prof Julia Newton, Dr Wa=
n Ng and her colleagues, and 3 other research groups in the UK, have now be=
en awarded grants totaling =A31.65 million.
Medical research funding of =A31.65 million for ME/CFS is not a huge sum; t=
he MRC's gross research expenditure was =A3758.2 million in 2009/10, for ex=
ample. However, the allocation of these monies under a "pathophysiology" ca=
ll, culminating in the award of grants for research that is overwhelmingly =
"biomedical" rather than "psychosocial" in nature, is a significant achieve=
ment for which Prof Stephen Holgate, the ME/CFS charities and the MRC itsel=
f deserve congratulations. The task now is to ensure that Class I funding c=
ontinues to be available, year-on-year, for biomedical research into a dise=
ase that has been overlooked for far too long.
_______________________________________________________
Note 3. Neurocognitive impairment in ME/CFS
Neurocognitive problems are one of the most frequent and disabling symptoms=
associated with ME/CFS. In one investigation, 89% of patients reported mem=
ory/concentration problems, while in another large study memory/attention d=
eficit problems were reported by approx 90% of 2073 consecutive patients. C=
rucially, patients often report that their cognitive problems are often mad=
e worse by physical or mental exertion. But do such self-reported "anecdote=
s" about cognitive symptoms also show up as measurable deficits on objectiv=
e cognitive testing in a clinical setting?
Meta-analysis is a method of combining results from a range of studies to o=
btain an overall estimate of the "true" effect of a treatment. In 2010, res=
earchers at the University of Adelaide, South Australia published a meta-an=
alysis (Cockshell et al, Psychol Med. 2010 Aug;40(8):1253-67) of all releva=
nt clinical trials examining cognitive functioning in people with ME/CFS, w=
ith the aim of identifying the pattern and magnitude of these deficits. Ove=
rall, they found a very mixed bag of 50 studies (made up of 1577 patients a=
nd 1487 controls) published between 1988 and 2008 from which, nevertheless,=
a clear and very revealing pattern emerged on detailed examination.
The most significant cognitive deficits were found in "attention" (encompas=
sing attention span and working memory), "memory"(examined from verbal and =
visual memory tests, mostly memory for word lists) and reaction time (asses=
sed as responses to both simple and complex choice stimuli) - consistent w=
ith the memory and concentration problems that patients themselves complain=
about. In contrast, deficits were not statistically apparent on tests of "=
fine motor speed", "vocabulary", "reasoning" and "global functioning" - sug=
gesting that the "higher order" cognitive abilities, such as language, reas=
oning or intelligence remain unimpaired. And importantly, the majority of s=
tudies that examined the impact of self-reported depression on cognitive fu=
nctioning failed to find a relationship, indicating that depression was not=
responsible for most cognitive impairments.
The range of these studies and the clarity of the findings leave no doubt t=
hat people with ME/CFS have moderate to large impairments in simple and com=
plex information processing speed and in tasks requiring working memory ove=
r a sustained period of time. As the authors point out, the deficits in per=
formance are around 0.5-1.0 standard deviations below that of healthy peopl=
e, a fact which explains the significant impact cognitive problems have on =
patients' day-to-day activities and quality of life.
This overview has been extracted from ME Research UK's magazine, Breakthrou=
gh, Autumn 2010 (page 18) http://www.meresearch.org.uk/information/breakth=
rough/Breakthrough_Autumn2010.pdf
Dr Neil C. Abbot
Operations Director
ME Research UK
The Gateway
North Methven St
Perth PH1 5PP, UK
ME Research UK is a Scottish Charitable Incorporated Organisation (charity =
number SC036942) funding biomedical research into ME/CFS. Our principal aim=
is to commission and fund high-quality scientific (biomedical) investigati=
on into the causes, consequences and treatment of ME/CFS, but we also have =
a mission to "Energise ME Research" http://www.meresearch.org.uk/
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