Orchard Therapeutics announces extension of its collaboration with Manchester University to include Sanfilippo Syndrome type B
Orchard Therapeutics Limited, announces today that it has acquired an exclusive license to develop lentivirus-based autologous ex-vivo gene therapy for Sanfilippo syndrome type B (or MPS-IIIB) from The University of Manchester, UK.
The technology, developed in Professor Brian Bigger’s laboratory, and recently published in the journal Brain, involves the use of a high-titre lentiviral vector to drive the expression of a codon-optimized α-N-acetylglucosaminidase (NAGLU) gene under the control of the myeloid-specific CD11b promoter (LV.CD11b.NAGLU).
MPS-IIIB is a rare neurodegenerative inherited lysosomal storage disease caused by mutations in the NAGLU gene. The disease, which affects children as early as 2 years of age, results in severe and rapidly progressive brain disease and neurological symptoms. There is currently no effective treatment option for MPS-IIIB.
This programme in MPS-IIIB complements the existing collaboration program between Orchard, The University of Manchester and Manchester University NHS Foundation Trust in MPS-IIIA. Autologous ex-vivo lentiviral haematopoietic stem cell gene therapy is anticipated to correct neurological manifestations through the engraftment of subpopulations of haematopoietic stem cells in the central nervous system, thereby providing supranormal and widespread enzyme expression throughout the brain. In both MPS-IIIA and MPS-IIIB, preclinical studies have produced encouraging results showing a normalization of heparan sulphate levels in the brain and peripheral organs, as well as neurological disease correction.
Dr Jesus Garcia-Segovia, Orchard’s VP Clinical Development, CNS and Metabolic Disorders stated: “The incorporation of MPS-IIIB into our development pipeline is a significant milestone in the consolidation of our neurometabolic franchise, which is currently focused on the development of autologous ex-vivo haematopoietic stem-cell gene therapy for children suffering from MPS-IIIA. We are very excited at the possibility of bringing effective treatments capable of addressing the high unmet medical need in children suffering from these devastating conditions”.
Prof Brian Bigger, Professor of Cell and Gene Therapy in the Faculty of Biology, Medicine and Health, The University of Manchester commented: “It’s incredibly exciting for us to work with our trusted partner Orchard Therapeutics to translate another autologous ex-vivo gene therapy that has demonstrated efficacy in a preclinical mouse model of MPS-IIIB into clinical development and scale-up”.
Dr. Andrea Spezzi, Orchard’s Chief Medical Officer added: “MPS-IIIA and MPS-IIIB are devastating diseases. Orchard and its collaborators are highly motivated to develop gene therapies to address the root cause of these disorders and will work tirelessly to make treatments available to patients as soon as possible. We are now focusing all our efforts on completing the preclinical activities required to enable the start of clinical studies in MPS-IIIA towards the end of 2018 and thereafter in MPS-IIIB”.
Orchard’s development pipeline of autologous ex-vivo gene therapies includes novel treatments for primary immune deficiencies, and inherited metabolic disorders including other undisclosed early and late-stage programmes.
About MPS-IIIA (Mucopolysaccharidosis type IIIA or Sanfilippo syndrome type A)
MPS-IIIA is a rare neurodegenerative lysosomal storage disease caused by mutations in the sulfoglycosamine sulfohydrolase (SGSH) gene. There are no effective treatments for MPS-IIIA to date. The disease affects children in early life causing a progressive decline in cognitive and behavioural function and a subsequent decline in motor function. It results in severe dementia and early death, usually in the teens or early twenties. Orchard’s autologous ex-vivo gene therapy for MPS-IIIA, OTL-201, was awarded orphan drugs designations by the European Medicines Agency (EMA) and FDA.
About MPS-IIIB (Mucopolysaccharidosis type IIIB or Sanfilippo syndrome type B)
MPS-IIIB is a severe inherited autosomal recessive disorder caused by mutations in the NAGLU gene. Affected children exhibit the first signs of development delay between 2 or 3 years of age, and suffer from severe central nervous system degeneration, with progressive cognitive impairment and behavioural problems, alongside more attenuated somatic symptoms. Life expectancy is 15–20 years. There are currently no treatments approved for MPS-IIIB.
Professor Bigger’s publication on autologous ex-vivo lentiviral gene therapy utilizing myeloid-specific CD11b promoter (LV.CD11b.NAGLU) in the journal Brain can be found under the DOI 10.1093/brain/awx311; https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awx311/4657148
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