UCL School of Pharmacy


Development of gene therapy for Niemann-Pick Type C Disease

3 April 2014


Vials for blood samples with lids in various colours

Project Description: Niemann-Pick Type C Disease (NPC) is a devastating neurodegenerative lysosomal storage disorder caused, in 95% of cases, by a mutation in the NPC1 gene. It is an intractable disease for which conventional medicines holds no route to therapy. Consequently, children that present with symptoms during the antenatal or infantile stage usually do not survive past the first few months or years of life. There is an overwhelming need to develop novel therapies for NPC.

Gene therapy could be a means of treating this disease and requires investigation. This is supported by continuing improvements in viral vector technology and successes in gene therapy clinical trials for neurodegenerative disorders. The aim of this project is to develop novel viral vectors that express therapeutic NPC1 gene. These vectors will be used to further dissect the mechanisms underpinning this disease using in vitro and in vivo models. We will also conduct a pre-clinical assessment of early intervention gene therapy in a mouse model of NPC using a new generation of viral gene delivery vectors.

Researchers: Project Lead at UCL - Dr Ahad Rahim, Lead Researcher - Mr Michael Hughes.

Collaborators: Professor Frances Platt (University of Oxford); Dr Simon Waddington (UCL Institute for Women’s Heath); Dr Steven Howe (UCL Institute of Child Health) and Professor Michael Duchen (UCL). Funding: Niemann-Pick Disease Group and Niemann-Pick Research Foundation


1. Rahim AA, Wong AM, Hoefer K, Buckley SM, Mattar CM, Cheng SH, Chan JK, Cooper JD, Waddington SN (2011) Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of CNS cell types and extensive transduction of the nervous system. FASEB J 25: 3505-3518.

2. Rahim AA, Wong AM, Buckley SM, Chan JK, David AL, Cooper JD, Coutelle C, Peebles DM, Waddington SN (2010) In utero gene transfer to the mouse nervous system. Biochem Soc Trans 38: 1489-1493.

3. Rahim AA, Buckley SMK, Chan JKY, Peebles DM, Waddington SN (2011) Perinatal gene delivery to the CNS. Ther Deliv 2: 483-491.