MPSIIIB Sanfilippo now included in Orchard Therapeutics and Manchester University collaborative programme

Strand of DNA in MPS Society colours

MPSIIIB Sanfilippo now included in Orchard Therapeutics and Manchester University collaborative programme

Strand of DNA in MPS Society colours

Orchard Therapeutics, a clinical-stage biotechnology company dedicated to transforming the lives of patients with rare disorders through innovative gene therapies, has announced that it has acquired an exclusive license to develop lentivirus-based autologous ex-vivo gene therapy for Sanfilippo syndrome type B (or MPSIIIB) 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).

MPSIIIB 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 MPSIIIB.

This programme in MPSIIIB complements the existing collaboration programme between Orchard Therapeutics (Orchard), The University of Manchester and Manchester University NHS Foundation Trust in MPSIIIA. 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 MPSIIIA and MPSIIIB, preclinical studies have produced encouraging results showing a normalisation 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 MPSIIIB 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 MPSIIIA. 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 MPSIIIB into clinical development and scale-up”.

Dr. Andrea Spezzi, Orchard’s Chief Medical Officer added: “MPSIIIA and MPSIIIB 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 focussing all our efforts on completing the preclinical activities required to enable the start of clinical studies in MPSIIIA towards the end of 2018 and thereafter in MPSIIIB”.

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.

More information about Sanfilippo MPSIIIA and MPSIIIB

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 here.

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