Scientists in Manchester, who have developed a stem cell gene
therapy to reverse a fatal childhood illness, have agreed to work
with a new therapeutics company to test it in a human trial.
Manchester and Central Manchester University Hospital NHS
Foundation Trust (CMFT)
researchers have developed the pioneering approach for Sanfilippo
disease (also known as mucopolysaccharidosis type III or MPS III) -
a genetic condition for which there is currently no effective
The most common of the four types of Sanfilippo (type A) affects
around 100 children in the UK, or one in 89,000 births, and it is
this type that is targeted by the new treatment.
Sanfilippo is caused by a lack of the SGSH enzyme, which helps
to break down and recycle long chain sugars. This results in a
build-up of sugars in the body and particularly the brain.
Children with Sanfilippo begin showing symptoms of
hyperactivity, severe behavioural problems and miss developmental
milestones as toddlers. As they get older they show symptoms
similar to dementia, and most never achieve a mental age beyond two
years. Later they will experience seizures and difficulties in
walking and swallowing. It is invariably fatal, with most children
dying around the age of 18 years.
Following a licence agreement with Orchard Therapeutics, a new
UK-based clinical-stage biotechnology company, the gene therapy
developed in Manchester will be trialled in humans. The University
of Manchester's technology transfer company, UMI3, negotiated the terms of the major
deal with Orchard Therapeutics.
Dr Brian Bigger, who leads the Stem Cell and
Neurotherapies Laboratory at The University of Manchester and
developed the technique in partnership with the Trust scientists,
said: "This license agreement with Orchard will allow us to take
the technique we have developed to the next and crucial stage of
trials in humans. We are hopeful that this treatment may help to
treat the early onset dementia in these patients and saving
If we can show that it is possible to treat single gene brain
diseases, such as Sanfilippo, with stem cell gene therapy, this
will pave the way for treating other lysosomal storage and
The treatment works by genetically correcting the patients' own
stem cells and implanting them into bone marrow to release the
missing enzyme in a way that reaches the brain, thereby correcting
The new study will take place at CMFT, supported by
the NIHR/Wellcome Trust Manchester Clinical Research
"There are currently no effective treatments available to
children affected by Sanfilippo disease. We hope that this work
will help to halt the progression of this devastating condition,"
added Dr Simon Jones, Consultant in Paediatric Inherited Metabolic
Disease at Saint Mary's Hospital and the Manchester Centre for
Professor Robert Wynn, Consultant Paediatric
Haematologist at Royal Manchester Children's Hospital and chief
investigator for the clinical study explained: "This new clinical
study aims to explore whether we can use stem cell gene therapy to
produce blood cells that express corrected versions of the missing
"We know that in conditions similar to Sanfilippo blood cells
from a bone marrow donor can deliver such enzymes effectively. This
new gene therapy builds on the decades of experience of CMFT
physicians in bone marrow transplantation of children with these
other metabolic diseases."
Earlier attempts to cure the illness with a bone marrow
transplant were unsuccessful as not enough enzyme was produced to
have an effect, but the Manchester team has developed a way of
overproducing the SGSH enzyme specifically in bone marrow white
This was achieved by developing a lentiviral vector - a tool
commonly used by molecular biologists to deliver genetic material
into cells - specifically for use in humans, which will be tested
in the trial. The lentiviral vector delivers
the SGSH gene to bone marrow cells, which, when
implanted into the body are able to traffic to both the bone marrow
and the brain and deliver SGSH enzyme throughout the body, thus
correcting the disease.
Recently a related illness metachromatic leukodystrophy has been
treated by Italian scientists using a similar approach, with
extremely promising results in patients.
The Manchester team used a similar lentiviral vector to the
Italian team, but improved the design to make it more specific to
the white blood cells that traffic into and engraft in the brain
after a bone marrow transplant (monocytes/microglia). This improves
brain targeting and effectiveness.
Professor Bobby Gaspar, Chief Scientific Officer of
Orchard Therapeutics said:
"Stem cell gene therapy has shown promising effects in several
different diseases and we are hopeful that this technology will
change the lives of children with Sanfilippo type A and other
monogenic bone marrow disorders in the near future."
Life Sciences Minister, George Freeman MP, said: "This
pioneering trial, led by UK researchers in partnership with a UK
company, underlines exactly why we invest £1 billion each year
through the National Institute for Health Research. This new gene
therapy has the potential to change the lives of children with this
dreadful condition, and will undoubtedly help to cement the UK's
position as a world-leader in medical research."