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Formal opening of the new NAC scanner on 2 November, 2012 by Dame Sally C Davies FMedSci, Chief
Medical Officer and Chief Scientific Adviser, Department of Health. The photo shows, from left to right,
Professor Sir Mark Pepys FRS FMedSci, Director of the Wolfson Drug Discovery Unit, Dame Sally and
Professor Philip Hawkins FMedSci, Director of the NAC.
Introduction
Amyloidosis is a serious but treatable disease. The National Amyloidosis
Centre (the NAC) has been at the cutting edge of treatment and research into
all aspects of amyloidosis for over 25 years. We are situated at the Royal
Free Hospital in Hampstead, London and are part of the University College
London (UCL) Division of Medicine. Since 1999 we have been responsible for
the UK national caseload of amyloidosis, so patients with amyloidosis are
referred to us from the entire UK, and from around the world.
There has been great progress in understanding, diagnosis and treatment of
amyloidosis in recent years. In 1987 we developed the SAP scan, the only
existing method for non-invasive diagnosis and comprehensive follow up of
amyloidosis in all parts of the body. The NAC is the only place in the world
where the SAP scan is routinely available, and we perform about 3,000 scans
per year. This number is expected to increase with the installation of our
new scanner, partly funded by the Royal Free Charity. The photo above was
taken at the formal opening of the scanner.
We follow all our patients regularly and maintain close contact with other
physicians involved in their management to ensure that they receive the best
and most effective treatments available. This is the first official NAC
newsletter. It includes information about aspects of amyloidosis, a patient’s
story, news about on-going developments and research at the NAC and
articles about some of the impressive fundraising efforts by patients and
their families. For detailed information about amyloidosis and the NAC,
please visit our newly launched patient information website at:
http://www.nationalamyloidosiscentre.org.uk/.
ISSUE 1: March 2013
IN THIS ISSUE
Introduction
1
Amyloidosis fact-file
2
Focus on
AL amyloidosis
2
A patient’s story
Jo Jerden
4
More about
amyloid neuropathy
6
Fundraising
7
Donations
8
National Amyloidosis Centre, UCL Division of Medicine, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK
www.ucl.ac.uk/medicine/amyloidosis
2  Issue 1: March 2013
Amyloidosis fact-file
Most people have never heard of amyloidosis until they, or their
loved one is diagnosed with the condition.
This can be very hard, and many patients feel isolated.
Just explaining the diagnosis to family and friends can be
difficult.
This fact-file is intended to provide a simple resource to help you
understand and explain some basic facts about the condition.
In each issue of this newsletter, the fact-file will focus on one of
the different types of amyloidosis. For the first issue, we have
chosen AL amyloidosis, the most common type of amyloidosis.
Future issues will address the other types.
Amyloidosis in brief
Amyloidosis is a rare disease caused by abnormal deposition and
accumulation of proteins in the tissues of the body. Amyloid
deposits are primarily made up of protein fibres known as
amyloid fibrils. These amyloid fibrils are formed when normally
soluble body proteins aggregate (clump together) and then
remain in the tissues instead of safely going away. About 30
different proteins are known to form amyloid deposits in humans.
Amyloid deposits cause disease by gradually accumulating within
organs and thereby disrupting the structure and damaging the
function of the affected tissues. In some cases, previously healthy
organs can be substantially replaced by extensive amyloid
deposits. Amyloidosis is usually a systemic disease. This means
that many body organs and systems may be affected.
National Amyloidosis Centre News
Focus on
AL amyloidosis
AL amyloidosis is the most common type of amyloidosis in
developed countries. In the past it was known as “primary
amyloidosis”. In the UK about 500-600 new cases are diagnosed
each year and it is the cause of death in between 0.5 to 1 out of
every 1000 people.
AL amyloidosis is the diagnosis in about 60% of the patients
treated at the NAC and this condition is never hereditary. AL
amyloidosis is equally common in men and women and although
most patients with AL amyloidosis are aged over 45, it
occasionally occurs at younger ages.
In AL amyloidosis there is an underlying disorder in which there is
overproduction of amyloid forming proteins called light chains.
Light chains are part of antibodies, and are also known as
immunoglobulins. They are produced by a type of immune
system cell called plasma cells. In AL amyloidosis abnormal
plasma cells which are usually, but not always, located in the
bone marrow produce amyloid forming light chains or light chain
fragments.
Each normal antibody consists of 4 protein chains, as shown in
the illustration below. The red chains are called the “light chains”
and the grey chains are called the “heavy chains”.
Different types of amyloidosis
Different types of amyloidosis are named according to the
proteins which form the amyloid fibrils. All have the initial letter
“A” denoting amyloidosis and other letter(s) identifying the
particular protein (known as a “precursor protein”) which forms
amyloid fibrils within the amyloid deposits. For example:
AL amyloidosis: Light chains (fragments of monoclonal
immunoglobulins (antibodies)) are the amyloid precursor protein.
AA amyloidosis: Serum amyloid A protein (SAA), a blood protein
whose levels rise when there is prolonged inflammation, is the
amyloid precursor protein.
This was formerly known as
secondary amyloidosis.
ATTR amyloidosis: Transthyretin (TTR), a normal blood protein,
present in everybody, is the amyloid precursor protein. Some
forms of ATTR amyloidosis are hereditary, such as familial amyloid
polyneuropathy (FAP), and others are not inherited, such as senile
systemic amyloidosis.
Aβ2M amyloidosis: Beta-2-Microglobulin (β2M) is the amyloid
precursor protein.
AFib amyloidosis: Fibrinogen is the amyloid precursor protein.
A wide variety of other proteins can form amyloid in the various
rare, hereditary types of amyloidosis.
Abnormal free light chains can be measured in about 95% of
patients with AL amyloidosis and:
• about 80% have a subtle plasma cell abnormality, which
may be called by a number of names, including:
• MGUS (monoclonal gammopathy of uncertain
significance)
• plasma cell disorder
• plasma cell dyscrasia
• paraprotein disorder
• about 20% have a type of bone marrow cancer called
myeloma, and also known as multiple myeloma.
In AL amyloidosis, amyloid deposits may affect any part of the
body except for the brain. Usually one or two organs are
predominantly affected (known as the “dominant” organs). The
structure and properties of the abnormal light chain proteins
forming the amyloid fibrils are slightly different in every single AL
amyloidosis patient and symptoms also vary widely, depending on
which organs contain amyloid deposits and the extent to which
the deposits affect organ function.
National Amyloidosis Centre News
Issue 1: March 2013  3
Principles of treatment
Treatment of all types of amyloidosis is currently based on the
following principles:
• reducing the supply of amyloid forming precursor proteins
• supporting the function of organs containing amyloid.
SAP scans in thousands of patients with various forms of
amyloidosis have shown that when amyloid precursor protein
supply is controlled:
• existing amyloid deposits often regress (become smaller)
• new amyloid deposits stop appearing
• organ function is often preserved and may also recover.
The precise way in which deposition of amyloid causes disease is
not fully understood. There may be poor correlation between the
amount of local amyloid and the extent to which organ function is
lost. Although heavy amyloid load is invariably a bad sign, active
deposition of new amyloid is often more closely linked to
worsening disease than are stable, longstanding deposits.
Patients with AL amyloidosis may complain of general problems
such as weight loss, fatigue, weakness, loss of appetite and easy
bruising. They may also develop:
• kidney disease (> 90%)
• heart disease (90%)
• nervous system disease:
• peripheral neuropathy
• autonomic neuropathy
• gut disease
• enlarged liver or liver failure
• enlarged spleen or problems with spleen function
• macroglossia (enlarged tongue) - rare but only seen in AL
amyloidosis
• joint disease-rare
• skin disease:
• easy bruising
• lesions on face and upper trunk - papules, nodules and
plaques.
AL amyloidosis is a very serious condition. If left untreated it is
progressive and may lead to death within a year. However, many
patients benefit considerably from current standard therapies for
AL amyloidosis, and survive for many years after the diagnosis,
with improved health and good quality of life. In addition, there
have been substantial recent advances in the treatments
available, so there is cautious optimism regarding the future.
In AL amyloidosis, treatment is directed towards the abnormal
plasma cells (usually in the bone marrow), which produce the
abnormal light chains that form amyloid deposits. Treatment
regimes are referred to as “chemotherapy.” The drugs used are
similar to those used in the related condition of multiple
myeloma. In recent years, newer types of drugs have been
introduced, which appear to be more effective than previous
regimes, with fewer side effects.
Tailored treatment
AL amyloidosis is a very varied disease. Each patient’s disease is
caused by their own, unique abnormal light chains and
manifestations of illness differ considerably between patients.
The most suitable treatment for each individual depends on a
number of factors including:
• age
• quantity of amyloid
• organs affected-heart and kidney function are especially
important for treatment decisions
• other diseases and general health
• personal preference.
Treatment should be individually tailored after consultation with
the NAC doctors.
Occasionally chemotherapy is not
recommended, under the following circumstances:
• mild or non-progressive amyloidosis
• localised amyloidosis
• a patient who is too ill to benefit from chemotherapy
(very rare).
For most patients, doctors at the NAC do recommend drug
treatment. There are several drugs which have been shown to:
• halt progression of AL amyloidosis
• improve symptoms
• prolong patients’ lives.
National Amyloidosis Centre News
4  Issue 1: March 2013
A patient’s story: Jo Jerden
My difficulties began in November 2010, when I was 42
years old. Until this time I had been very fit and healthy,
leading a full life working in a responsible position as an
Estates Manager while studying for a degree and running
the family home. At the beginning of November my
husband and I went on a 26 mile bike ride during a long
weekend in the New Forest. On returning home the tops of
my feet were quite sore and my back ached - I thought I
must have strained them with the cycling. They did not
improve and so I visited our
osteopath who usually solves any
such problem very efficiently.
This time, however, the treatment
just resulted in agonising pain all
over. I was now also experiencing
a feeling of complete exhaustion
each evening when I arrived
home, and would have to sit down
to prepare dinner. On going to
bed I would feel like I had run a
marathon, the pressure of the
mattress on my legs and arms
caused pain all over. The worst
pain of all though was in my feet.
There was no visible explanation
for the pain, except in the
morning there would be some
swelling generally across the base
of my toes.
The pain was like nothing I had
ever experienced. It felt like
someone hammering on the tops
of my feet, while around my
ankles it was like someone
pushing glass shards into them. I
experienced
throbbing
and
shooting pains under the nails of
my toes, and when I pointed my toes it felt as if the tendons
were tearing. I could not bear bed clothes near my feet and
bath water was intolerable. High heels, which I had always
favoured, were out of the question. Gradually the pain
spread from just at night and walking became difficult. It
felt as if all the skin had been stripped away and I was
walking on my bone ends. I was getting increasingly tired
due to lack of sleep, as most nights were spent in tears not
knowing where to put myself. I had to lock my office door
and take a lunch time nap in order to get through the day.
My husband and I had to sleep in separate beds so that he
at least could get some sleep.
During December 2010 my weight began to plummet and I
found it difficult to retain food as I would be sick frequently.
I first visited the doctor during late November / early
December due to the mysterious foot pain, but left feeling
rather stupid as there was nothing to see and during the
day the pain was not initially present. I returned and saw
another doctor who was similarly perplexed, but he did
send me for some blood tests. I booked a private
appointment with a podiatrist who found nothing
mechanically wrong with my feet.
I also went to a sports
physiotherapist, who felt the
problem was something neural
but could not pin point it. By now
I was only able to limp around in
trainers which had to be undone.
An abnormal paraprotein reading
was detected in my blood and the
doctor referred me to a
haematologist in January 2011.
She examined me with a view to
myeloma but decided this was
unlikely and therefore recorded
the diagnosis as MGUS and
referred me to a neurologist for
further tests for the pain.
After seeing the neurologist I
underwent numerous scans,
lumbar puncture tests and the
like. Every test came back normal.
In May 2011 I signed off work for
a period of time due to my illness
and stress from a number of
traumatic family events. I was
taken to hospital by ambulance
following a collapse in the garden in July 2011. I now know
this was caused by autonomic neuropathy. The neurologist
thought that I had a small fibre neuropathy but could not
identify the cause nor could he explain the mysterious
collapse. I had been on pregabolin which did not help and
made me very groggy. I was also taking co-codamol. My
prescription was altered to duloxetine which helped
immensely and I still take this to combat the nerve pain.
I was referred to King’s College Hospital in July 2011, and I
was sent for a bone scan and CT scan and mammogram in
August 2011. I was given a skin biopsy and autonomic
National Amyloidosis Centre News
function tests in September 2011. By now my bowel habits
had become a problem with alternating constipation and
diarrhoea. The skin biopsy confirmed a small fibre
neuropathy and the autonomic function tests confirmed
both sympathetic and parasympathetic defects. The
neurologist still could not pinpoint the cause and in January
2012, as a long shot, it was suggested that my case be
reviewed by NAC - the neurologist considered this an
unlikely cause of my neuropathy.
Amyloid neuropathy

Amyloid neuropathy is common in patients with AL
amyloidosis. It is also seen in patients with familial
amyloid polyneuropathy (FAP), the most common
inherited type of amyloidosis. Like Jo Jerden, many
patients experience gradually progressive symptoms
for some time before the diagnosis is made. Doctors
may be puzzled as to what is causing the symptoms,
as the complaints may appear vague. Amyloid
neuropathy includes peripheral neuropathy and
autonomic neuropathy. For more details, see the
article on the next page.
In February 2012 I attended my first appointment at the
NAC and a simple SAP scan confirmed that I had
amyloidosis. The unit and staff are set apart from any other
hospital unit I have attended by their kindness and
understanding manner. It had taken approximately 16
months from my first visits to the doctor to reach a
diagnosis and amyloidosis was not suggested until the very
last resort. Interestingly, my sister who is a nurse in USA
and works with a neurologist, had been suggesting I should
be tested for amyloidosis for the best part of a year - I had
passed on her concerns but it was considered unlikely.
In March 2012 I began a course of chemotherapy taking
lenalidomide with dexamethasone. The side effects of
tiredness, and nausea got progressively worse as the 6
months went on. I felt that my mental health was also
affected. The diarrhoea became so bad that I was terrified
to leave the house as I would be caught completely
unawares and there seemed to be no solution. I took to
wearing incontinence pants if I had to leave the house at all
and became very depressed with suicidal thoughts entering
my head. I went to the doctor on two occasions and it was
suggested that I should take antidepressants which I was
reluctant to start. My husband and I now had little social
life and things were very difficult. I was so nauseous and
Issue 1: March 2013  5
with the constant diarrhoea I was losing weight very rapidly
and weighed barely 7 stone (I weighed 10 stone before I
became ill).
I visited the NAC again in August 2012 and had another SAP
scan. There was little change from the initial scan but my
paraprotein levels had fallen from 12 to 3. It was
recommended that I should continue the chemotherapy for
a further 6 months to try to bring the paraprotein down
further. Monitoring light chains in my case appeared to be
unhelpful as these are fairly normal for me. I explained that
I could not continue with the current chemotherapy drugs
as I had no quality of life anymore. The steroid was altered
from dexamethasone to prednisolone and very quickly an
improvement was noticeable - it transpires that mental
health problems can be a side effect of prolonged
treatment with high doses of steroids. I could now eat and
retain food, and the imodium began to take effect: the
diarrhoea was not cured, but was under better control. I
felt less depressed and was able to exercise. Over a month I
managed to regain 1 stone in weight. I started to venture
out again and gradually regained some confidence about
hopefully not being caught in public with episodes of
diarrhoea.
I am currently about to start cycle 8 and we have regained
some social life. I even returned to work in November
albeit on a part time basis. However, my paraprotein level
has not decreased any further and this may impact the
doctors’ decisions regarding further chemotherapy. My
walking and general pain levels have improved greatly, but
the bowel difficulties remain the most debilitating problem,
although large daily doses of imodium are helping.
The future is uncertain and I have found the counselling
offered by the supportive therapies unit at our local
hospital to be invaluable. I would thoroughly recommend
this even if (like me) you are not generally in need of such
services. If nothing else it saves burdening your loved one
with your fears and concerns. They then worry themselves
in turn and may have no-one with whom to share the
burden.
It is difficult when you believe you have your life mapped
out and something unexpected turns it upside down. In
order to prevent yourself dwelling on the downside, it is
important to understand what is necessary about the illness
and to learn to manage the symptoms you experience, but
then to try to get back to as normal a life as possible.
Otherwise you just sit at home waiting for the next
complication. Hopefully a cure will not be long in coming!
National Amyloidosis Centre News
6  Issue 1: March 2013
More about amyloid neuropathy
Peripheral neuropathy:
This is caused by amyloid deposits in the nerve fibres supplying the arms and legs. At first there are unpleasant sensations
in the feet, including burning pain and numbness, often worst at night. The symptoms then gradually extend up the legs,
then later to the hands, then the arms. Some patients experience allodynia. This means pain induced by stimuli that are
not usually painful, such as the contact between the legs and the mattress while lying in bed. Later there may be loss of
sensation and weakness in the limbs. Walking may become difficult, with loss of balance. Some patients experience loss of
sensation in the feet and legs but no pain.
Autonomic neuropathy:
Autonomic functions include normal functioning of the gut, maintenance of normal heart beat and blood pressure, urinary
and sexual function. If there are amyloid deposits in the nerve fibres supplying these areas of the body, some or all of the
symptoms below may appear. Most of these symptoms usually appear after the onset of peripheral neuropathy. Erectile
dysfunction may appear early on, before peripheral neuropathy.
Symptoms of autonomic neuropathy:
•
Gastro-intestinal (gut) problems:
•
nausea, vomiting (sometimes after eating), diarrhoea (after
eating or at night),severe constipation, alternating diarrhoea
and constipation
•
Heart and circulation problems:
•
orthostatic hypotension: dizziness, blurred vision or lightheadedness on standing up (due to drops in blood pressure),
disturbances of heart rhythm
•
Urinary problems (usually late):
•
pain on passing urine, difficulty passing urine
•
Sexual problems:
•
erectile dysfunction
•
General problems:
•
weight loss, fatigue, weakness, weight loss.
Diagnosis:
Peripheral neuropathy is a common condition, often caused by widespread disorders such as diabetes. Most patients with
these symptoms do not have amyloidosis. Neurologists may suspect the possibility of amyloidosis if there is also
autonomic neuropathy, a paraprotein (in AL amyloidosis), heart disease (AL amyloidosis and familial amyloid
polyneuropathy (FAP)), or a family history of neuropathy or cardiomyopathy (stiff heart muscle, in AL amyloidosis or FAP).
The diagnosis of amyloidosis may be confirmed or eliminated by performance of a biopsy and an SAP scan.
Treatment:
Medications that may help to alleviate neuropathic pain include gabapentin, pregabalin and duloxetine. Medical staff at
the NAC can give advice regarding appropriate foot care and footwear. This is important in order to prevent painless ulcers
at pressure points and to protect areas of the foot that lack sensation. If there is orthostatic hypotension, elastic stockings
may be recommended. Drug treatment with midodrine may also be helpful. Care should be taken to avoid dehydration if
there is vomiting and diarrhoea. Intravenous fluids and anti-nausea drugs may be necessary. There are drugs that can help
to control diarrhoea and constipation, and others that can help to combat erectile dysfunction. If there are disturbances of
heart rhythm, drug therapy or implantation of a pacemaker may be necessary.
National Amyloidosis Centre News
Issue 1: March 2013  7
Fundraising
Climbing for a cover-slipper
by Jo Jerden
I had always been fit and healthy before I developed AL
amyloidosis. The illness came as quite a blow and my husband
and I needed a positive focus to get us at least through the first 6
months. We both felt so helpless.
My husband came up with the idea of undertaking the Three
Peaks Challenge in order to raise funds for amyloidosis research.
This gruelling challenge involves climbing the three highest peaks
in the UK: Snowdon in Wales; Scafell Pike in England and Ben
Nevis in Scotland – attempting to complete all in less than 24 hrs
(http://www.thethreepeakschallenge.co.uk/).
I felt it would be a more focused effort if we were able to raise
funds for something specific and so enquired at NAC as to what
would be beneficial for them. I was advised that a cover slipper
machine would be particularly helpful to the histologists. Using
this machine they can prepare both clinical and research slides
but the cost of the machine is £23,000. This is currently a manual
task and with the provision of the cover slipper machine it will
additionally free up manpower for research purposes.
I felt that to try to raise the full £23,000 in one go was a bit
ambitious and we agreed to try to raise the money over a three
year period. So far the amount raised has exceeded £7,800 and
with further money pledged we anticipate it exceeding £8,000
which is far more than we had anticipated at this stage. The
JustGiving site is currently still reflective of the Three Peaks
Challenge, but it is planned to change this before too long to
represent the long term aim of the cover slipper machine, and we
will then record our other fundraising proceeds on the same site.
In the meantime the site is still open and donations can be made
at the following address:
http://www.justgiving.com/Stuart-Nigel-Simon-Phil-Jim-FionaBarbara-Jason.
The race is on
by Martin Bolton- Smith
I am running the Brighton Marathon on Sunday, 14 April 2013 in
aid of amyloidosis research. Since my wife Cheryl’s diagnosis with
this life-threatening incurable disease (AL amyloidosis) in 2011, I
have been fundraising for the NAC. It is the only centre in the UK
dedicated to research, diagnostic testing and providing advice on
treatment of this insidious rare disease from which about 3,000
people in the UK suffer. By the time patients are referred to the
NAC, the disease can be quite advanced. The NAC is at the
forefront of ground breaking international research into
Amyloidosis but rare diseases struggle for funding to develop new
treatments to improve the quality of life for sufferers.
I will have been running for about a year by 14 April marathon
day. I started from scratch gradually building up my fitness and
endurance. My journey has been quite a challenge as I have
found many aspects of the training tough and very intense.
Watching my dear wife’s suffering, and with the support of family
and friends, my determination to continue to raise awareness and
funds for research has never been stronger. Completing my first
half marathon in September 2012 gave me the necessary
confidence to persevere, gradually pushing myself harder so as to
be ready for the marathon.
The Brighton Marathon is one of the fastest and most popular in
the UK and attracts great crowds of supporters and runners. The
event starts with a loop of picturesque Preston Park, leaving the
city centre, and iconic Brighton Pavilion to head east along the
scenic coast road.
Please give generously to my appeal for Amyloidosis research.
Together we can provide the scientists and doctors working
doggedly at the NAC with much needed funds to find a cure for
this dreadful disease.
Thank you for your support. Donations can be made at the
following address:
http://www.justgiving.com/Martin-Bolton-Smith
National Amyloidosis Centre News
8  Issue 1: March 2013
Donations
To ensure that your donations go directly and exclusively to the NAC, please send directly to us or contact Beth Jones on
020 7433 2802 or [email protected]. Donations to the fundraising activities mentioned on page 7 will also come directly to NAC.
All university based medical research depends on funds that
are fought for in open competition (grants) from the
Government-funded Medical Research Council and other
charitable bodies. Their renewal depends on a successful
research programme and the NAC has an excellent track
record in this respect. However, there are constant shortfalls
and every penny from other sources is received with sincere
gratitude, and is used specifically and in its entirety for
amyloidosis research. You can make an online donation at:
http://www.ucl.ac.uk/medicine/amyloidosis/research_fund
or make a donation by post. Gift aid forms also available
online or from:
Beth Jones
National Amyloidosis Centre
Division of Medicine, Royal Free Campus
University College London
Rowland Hill Street
London NW3 2PF UK
UCL Medical School is part of University College London (UCL)
which is a registered charity. Due to changes in the Budget
nearly all gifts given to UCL now qualify for the Gift Aid
Scheme. This increases the amount of the gift by 28% without
any extra cost to the donor. It does so by allowing UCL to
claim back the basic rate tax paid by the donor. To qualify for
Gift Aid the donor must be a UK taxpayer and his/her
combined income and capital gains tax bill must equal or
exceed the amount UCL claims back on the gift. The gift can
be for any amount and applies to one-off gifts and regular gifts
made over a number of years. For UCL to claim the tax
benefits the donor must make a "Gift Aid Declaration". One
declaration will cover all future gifts and may be cancelled at
any time. Cheques should be drawn in favour of "UCL
Development Fund". This money is then transferred to the
Amyloidosis Research Fund together with the reclaimed tax. If
a donor does not qualify for the Gift Aid Scheme or does not
wish to contribute in this way, cheques should be made
payable to: "UCL Amyloidosis Research Fund".