Evaluation of blood brain barrier in MPS IIIB patients

  • Research type

    Research Study

  • Full title

    Evaluation of Blood Brain Barrier Integrity and Relationship to Structural Brain Abnormalities in MPS IIIB Patients Using Cerebrospinal Fluid/Serum Albumin Index (CSF-AI) and Multimodal Magnetic Resonance Imaging

  • IRAS ID

    136678

  • Contact name

    Suresh Vijay

  • Contact email

    Suresh.vijay@bch.nhs.uk

  • Sponsor organisation

    Synageva BioPharma Corp.

  • Research summary

    This is a non-treatment study to evaluate the blood brain barrier in MPS IIIB patients using cerebrospinal fluid / serum albumin index (CSF-AI) obtained by lumbar puncture and multimodal MRI. The study in funded by Synageva BioPharma Corp.

    MPS IIIB is a very rare and serious disease caused by a genetic defect resulting in a lack of the enzyme called NAGLU (or N-acetylglucosaminidase). There are currently no approved therapies for the treatment of MPS IIIB.

    Synageva BioPharma Corp is developing an enzyme replacement therapy for MPS IIIB called SBC-103. In general, intravenous administered enzymes do not get into the brain because of a physiological barrier between blood and brain, the so called ‘blood brain barrier’ and treatment of brain disease requires injections into the brain fluid. However, when SBC-103 was given intravenously to mice with MPS IIIB an increase of enzyme activity in their brain was found in addition to a reduction in Heparan Sulfate (substrate accumulated in MPS IIIB due to enzyme deficiency). These results suggest an impairment in blood brain barrier function of these animals. Before studying SBC-103 in human patients with MPS IIIB it has to be investigated if the blood brain barrier function in human patients with MPS IIIB is also impaired which is the purpose of the proposed study. Synageva BioPharma Corp intends to initiate studies with the purpose to develop intravenous enzyme therapy for MPS IIIB.

    6 patients will take part in the study with study duration of 6 weeks.

    The study will consist of 2 visits over approximately 2 weeks that will each last a few hours (screening visit and clinical visit) and a follow-up phone call 14 days after the clinical visit.

    Study assessments will involve physical exam, vital signs, medical history, blood, urine and cerebrospinal fluid tests, ECG, general anaesthesia, lumbar puncture, multimodal MRI and completion of a survey.

  • REC name

    East Midlands - Nottingham 1 Research Ethics Committee

  • REC reference

    13/EM/0335

  • Date of REC Opinion

    7 Nov 2013

  • REC opinion

    Further Information Favourable Opinion