Patient at Royal Manchester Children’s Hospital first to take part in trial of new treatment for rare inherited disease
Researchers at The Royal Manchester Children's Hospital
and The University of Manchester have recruited the first child
into a new study, which aims to evaluate the clinical effectiveness
of a treatment developed in Manchester.
by charity, The Society for Mucopolysaccharide Diseases (The MPS
Society), the study could alter the lives of patients with
Sanfilippo Disease - a fatal inherited condition which causes
progressive dementia in children.
Jack Baird, who is four years old and from Sunderland, has the
condition Sanfilippo Disease, also known as Mucopolysaccharidosis
(MPS) III, which affects around one in 85,000 people in the
Sanfilippo Disease is a progressive, genetic and
life-threatening disease for which there is currently no effective
treatment. The syndrome is diagnosed in childhood, with sufferers
experiencing deafness, hyperactivity and behavioural problems,
progressive developmental delay, and seizures during the later
stages of the condition. The condition is usually fatal in late
childhood or early adulthood.
"Jack's condition means that he doesn't speak much, is very
hyperactive and has to be sedated to go to sleep. Jack isn't very
interested in toys, but he loves going to school, and out
elsewhere. He enjoys going on the bus and going to Asda where
everybody knows him.
"We found out about the clinical trial through The MPS
Society, which was working with Dr Jones at The Royal Manchester
Children's Hospital. We got involved initially in 2012, by helping
to fundraise for the study. We know that the treatment is not going
to save Jack, but if the drug works we will have more time to make
more memories, and memories are priceless," explained Gemma Nelson,
The study conducted by the National Institute for Health
Research (NIHR) / Wellcome Trust Manchester Clinical Research
Facility at The Royal Manchester Children's Hospital builds on
initial research from The University of Manchester, which was
funded by the MPS Society. It aims to establish whether high doses
of the treatment Genistein Aglycone is effective in people with
People with Sanfilippo Disease have too much of the substance
heparan sulphate in their cells, particularly cells in the brain,
because they lack the enzyme that usually breaks the heparan
sulphate down. It is thought that Genistein Aglycone works by
blocking the production of heparan sulphate and associated damage
to the cells.
Genistein is a naturally occurring chemical found in soya
beans. In the study the researchers will use a synthetic version,
Genistein Aglycone, to maximise absorption through the gut.
Previous research in patients with Sanfilippo Disease has
shown that low doses of Genistein reduce the heparan sulphate in
the blood and urine, but are not sufficient to be effective in the
brain1. However, research at The University of Manchester using
higher doses of Genistein Alygone in the mouse model of Sanfilippo
Disease has shown that this is effective in reducing
Dr Brian Bigger, Chief Scientific Investigator for the study
from The University of Manchester said: "It is fantastic to see a
treatment we developed at The University of Manchester, in
collaboration with clinicians, reach the point where we can test
its effectiveness in patients. A US study published last year,
demonstrated the safety of high doses of Genistein Alygone in
patients with Sanfilippo Disease.
"This new study is the first to test the effectiveness of the
higher doses of Genistein, which are thought to be of the strength
required to see an effect in the brain. We are looking forward to
analysing the results of the trial and hope that the treatment will
Dr Simon Jones, Consultant in Paediatric Inherited Metabolic
Disease at Saint Mary's Hospital, Manchester, who is leading the
study explains: It's important for us to undertake research in rare
diseases, like Sanfilippo Disease, so that we can provide these
patients with the best possible care. During the later stages of
the disease, patients experience seizures, become wheelchair bound
and can have trouble swallowing.
"This new study is open to children aged 2-15 years old.
Patients taking part in the study will receive either Genistein
Aglycone or placebo (an inactive substance that looks like the
treatment) with food, over a period of 12 months. After 12 months
all children will receive Genistein Aglycone for a further 12
months", adds Dr Jones, who is also Honorary Senior Lecturer at The
University of Manchester.
Over the course of the study, patients will attend up to nine
clinic visits where they will have the level of heparan sulphate in
the spinal fluid measured, as well as undergoing physical
examinations and other assessments. It is anticipated that the
study will take around three years to complete.
"Sanfilippo Disease is rare, affecting about 150 children in
the UK. The MPS Society is proud of its collaboration with The
University of Manchester and The Royal Manchester Children's
Hospital, which will bring this important research to the clinic
and the patient. The funds raised so far allow for 24 children to
be on the Genistein clinical trial. We need to raise a further
£120,000, so that another six children can be involved and I'd like
to urge people interested in making a real difference to donate,
however big or small, and get in touch with The MPS Society," adds
Christine Lavery, Chief Executive of The MPS Society, the major
funder of the study.
The delivery of the study was supported by the National
Institute for Health Research (NIHR) Clinical Research