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PUMPA NEWSLETTER
APRIL 2009
PURINE METABOLIC PATIENTS’ ASSOCIATION
Registered Charity No 1019792
PUMPA’S SIXTEENTH ANNUAL GENERAL MEETING
The PUMPA AGM held on the 15th November 2008, in the
Histopathology Seminar Room, St Thomas’ Hospital was well
attended. The Chairman presented the Trustees’ annual report
covering the events of the year. PUMPA had welcomed four new
members over the past year. All committee members agreed to
remain in their current posts for 2009:
Chairman:
Hon. Treasurer:
Hon. Secretary:
Committee:
Professor David Perrett (acting)
Malcolm Reid
Dr Bridget Bax (acting)
Trish Bullen
Lynette Fairbanks
Nik Hoexter
Margot Lucas
Mary McBride.
The AGM was followed by lunch and an extremely interesting
seminar on ‘FOOD AND YOUR PURINE DISEASE’. The seminar
began with a presentation by Professor David Perrett on why diet
affects purine metabolism. Dr Liz Carrey then talked about the
biochemistry of purines in foods.
grow and multiply. Anti-metabolites also stop normal cells working
properly. This is why patients get side effects.
As many as 1 in 3 patients receiving 5-FU related therapy
experience dose limiting, and sometimes life-threatening, toxicity
that is largely avoidable. The reason why some patients experience
severe side-effects is highly likely to be due to differences in genetic
make-up. By predicting 5-FU or capecitabine toxicity, oncologists
can provide enhanced therapeutic choices for improved patient
outcomes (either by dose reduction or choice of alternative therapy).
Dihydropyrimidine dehydrogenase (DPD) deficiency is a
pharmacogenetic condition that results in toxicity when patients are
exposed to 5-FU. This condition is due to variations in the DPYD
gene, which encodes the DPD enzyme. Approximately 80-85% of
therapeutically administered 5-FU is normally degraded through
interaction with DPD, with the remaining 15% of active drug
available to kill cells. In the absence of typical DPD activity, the
expected amount of 5-FU is not degraded, potentially leading to
significant patient toxicity.
Dr Tony Marinaki of the Purine Research team then made a
presentation about Diet in the treatment of purine disorders, and this
was followed by Professor Jo Poulton from Oxford University who
spoke of her experience of one case of thymidine phosphorylase
deficiency and treatment with dietary restriction.
Dr Lynette Fairbanks then gave a very interesting presentation on
the association of fructose intake (the sugar found in soft drinks)
and the increased risk of developing gout. This was followed by Mr
Jeffrey James, who very kindly gave up his time to talk about his
firsthand experience as a gout sufferer.
PUMPA FUNDS RESEARCH INTO PREDICTING THE
TOXICITY OF ANTI-CANCER DRUGS
PUMPA recently made a research award to Dr Aathavan
Loganayagam of the Purine Research Laboratory and Department
of Gastroenterology at St. Thomas’ Hospital. His research aims to
produce a simple test that will predict whether a patient has a
predisposition to toxicity by chemotherapy drugs.
5-Fluorouracil (5-FU) and its pro-drug capecitabine are one of the
most commonly used groups of drugs to treat cancer. These drugs
are collectively termed the fluoropyrimidines. They are used to treat
many types of cancer including, breast, head and neck, stomach,
anal, colon and some skin cancers.
The fluoropyrimidines are part of a group of chemotherapy drugs
known as the anti-metabolites. Anti-metabolites are similar to
normal body molecules but they are slightly different in structure.
These differences mean that anti-metabolites stop cells working
properly. Anti-metabolites often stop cells making and repairing
DNA by inhibiting the synthesis of purine and pyrimidine
components. Cancer cells need to make and repair DNA in order to
Dr Aathavan Loganayagam at work in the Purine Research
Laboratories
Other genetic abnormalities have also been associated with
fluoropyrimidine toxicity. Reduction in the activity of the 5-FU
therapeutic target thymidylate sythetase (TS) and
enzymes
involved in folate metabolism, methylenetetrahydrofolate reductase
(MTHFR),
produced toxic effects that are clinically
indistinguishable from that which is associated with DPD deficiency.
It was previously thought DPD deficiency was not a significant
problem in U.K population. However, at the Purine Research
laboratory, Guy’s and St Thomas’ Hospital, we have from a cohort
of 47 patients with severe toxicity following fluoropyrimidine therapy,
identified that 20% carry a deleterious variation in the DPYD gene.
Currently, 450 patients who have had fluoropyrimidine
chemotherapy have been recruited. The aim is to identify the
various deleterious variations in the DPYD as well as the other
genes associated with severe fluoropyrimidine toxicity. The ultimate
aim is to produce a simple test that will detect the various
deleterious genetic variations, so that pre-treatment testing can be
performed that will predict predisposition to fluoropyrimidine toxicity.
This will guide oncologists as to the appropriate chemotherapy and
dosage to be used. This would not only greatly improve the quality
of life of cancer patients, but will also be cost-effective by reducing
hospital admissions. Drug toxicity, for example, is a major
healthcare cost and cause for prolonged length of hospital stay.
SUBSCRIPTIONS
With the New Year there comes the need for the renewal of
subscriptions. Many members have already paid, often with a
generous donation too, for which PUMPA is extremely grateful.
If you have not renewed yet, please complete the form below and
return it to PUMPA with your membership payment. Thank you.
PUMPA WEBSITE
To retain our standing with the Charity Commission, we need even
more members and so we urge you to recruit a relative, friend or
neighbour!
Due to a large amount of interest in our series of PUMPA booklets
“Caring for...” we have now made these available as PDF files on
PUMPA’s website. In response to requests by PUMPA members,
we have also added the speakers’ power point presentations from
our 2008 seminar on ‘Food and your purine disease’. To view these
please go to http://www.pumpa.org.uk.
Please contact the secretary (address below) if you would like
information about any local fund-raising efforts or news to be
included in the next Newsletter or on the website. Photographs
welcome too!
MEMBERSHIP INFORMATION
CHRIS AND PAULINE DOWIE RAISE FUNDS FOR PUMPA
PUMPA recently received two cheques from Chris and Pauline
Dowie, the proceeds from a fundraising music society choral
workshop and lunch they arranged in Wimborne. PUMPA would like
to say a big “Thank you” to Chris and Pauline for raising an
impressive £132 for PUMPA.
PUMPA members will be aware that Chris and Pauline have three
children who all inherited Familial Juvenile Hyperuricaemic
Nephropathy (FJHN). PUMPA is delighted to hear that after 15
years on dialysis and two previous failed kidney transplants, their
youngest son Edward, was called in the small hours of Monday 9 th
March 2009 by the Royal London Hospital to undergo a kidney
transplantation.
PUMPA wishes Edward all the very best for a successful
transplantation, and a good recovery.
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If the latter please inform your bank:
In a recent email to PUMPA, Chris stated that he had unashamedly
used Edward's kidney problems as a vehicle for making the subject
of FJHN widely known to the general public. He has also composed
music to celebrate certain landmarks in Edwards life - "Credo in
unum Deum" celebrated the fact that he had made it through his
first year of life against all the odds, and "From Darkness to Light"
much later on to celebrate Ed's victory over adversity.
PUMPA
AWARDS
INVESTIGATORS
TRAVEL
GRANTS
TO
YOUNG
PUMPA has awarded £2,000 towards the attendance costs of three
European young researchers who are to present their work at the
forthcoming 13th International Symposium on Purine and Pyrimidine
Metabolism, which is to be held in Sweden in June 2009.
SUMMER WINE TASTING
PUMPA’s annual tutored wine tasting
has been provisionally booked for Friday
10th July 2009. Please WATCH THIS
SPACE for further information!
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PUMPA
The Secretary, Dr Bridget Bax
Clinical Developmental Sciences
St. George’s University of London
Cranmer Terrace
London SW17 0RE
Email: [email protected]
Registered Charity No 1019792