Autologous ex-vivo gene modified HSCT in MPSII
Research type
Research Study
Full title
A phase I-II, study of autologous CD34+ haematopoietic stem cells transduced ex vivo with CD11B lentiviral vector encoding human IDS tagged with ApoEII in patients with neuronopathic mucopolysaccharidosis type II (nMPS II, Hunters syndrome)
IRAS ID
1004283
Contact name
Mohammed Zubair
Contact email
Sponsor organisation
University of Manchester
Eudract number
2021-000400-38
ISRCTN Number
ISRCTN12458940
Research summary
Mucopolysaccharidosis Type II is also referred to as MPS II or Hunter Syndrome. This is one of a family of diseases referred to as lysosomal storage diseases. MPS II is an x-linked inherited disease that means the person affected is missing a gene which codes for a specific enzyme (iduronate-2-sulphastase). Without this enzyme, two waste products build up in cells in the body causing the symptoms seen in MPS II – delayed development, progressive deteriorating mental status and behavioural problems. Currently, Enzyme Replacement Therapy (ERT) is the only approved treatment available for patients diagnosed with MPSII. However, ERT is a supportive therapy and is intended to alleviate symptoms and improve patient quality of life, rather than addressing the pathogenic mechanisms of the disease. To date, there is no effective disease-modifying treatment.
In children with other MPS conditions it has been shown that it is possible to provide enzyme to cells in the body by a bone marrow transplant – transplanted cells from a donor, able to make the absent enzyme and secrete to other cells through the blood, however, in MPS II a bone marrow transplant does not seem to deliver enough enzyme to the cells to get rid of the waste product.
The treatment proposed hopes to deliver increased amounts of enzyme to the cells by genetic manipulation of the patients own cells to include the missing IDS gene. The treatment process can be broken down in to 3 stages: Stem cell collection, chemotherapy conditioning and infusion of gene-modified cells. Patients will be followed up at regular intervals for 2 years initially. All of the treatment and follow-up conducted will be at Manchester University Foundation Trust.
Patients in order to be eligible will need to be between ≥3 months and ≤12 months at consent into the trial, with the severe (progressive neuronopathic) phenotype of MPSII.
REC name
London - West London & GTAC Research Ethics Committee
REC reference
22/LO/0386
Date of REC Opinion
9 Aug 2022
REC opinion
Further Information Favourable Opinion