- Seppen Jurgen, Bosma Piter Bilirubin, the Gold Within Circulation 2012;126 (22):2547-2549 [PubMed]
- van Dijk Remco, Mayayo-Peralta Isabel, Aronson Sem J., Kattentidt-Mouravieva Anja A., van der Mark Vincent A., de Knegt Rob, Oruc Nevin, Beuers Ulrich, Bosma Piter J. Disruption of HNF1α binding site causes inherited severe unconjugated hyperbilirubinemia Journal of hepatology 2015;63 (6):1525-1529 [PubMed]
- van Dijk Remco, Beuers Ulrich, Bosma Piter J. Gene replacement therapy for genetic hepatocellular jaundice Clinical reviews in allergy & immunology 2015;48 (2-3):243-253 [PubMed]
- de Waart Dirk R., Naik Jyoti, Utsunomiya Karina S., Duijst Suzanne, Ho-Mok Kam, Bolier A. Ruth, Hiralall Johan, Bull Laura N., Bosma Piter J., Oude Elferink Ronald P. J., Paulusma Coen C. ATP11C targets basolateral bile salt transporter proteins in mouse central hepatocytes Hepatology (Baltimore, Md.) 2016;64 (1):161-174 [PubMed]
PhD P.J. Bosma (Novel therapies for liver disease)
Adeno Associated Virus (AAV) mediated liver directed gene therapy for inherited unconjugated hyperbilirubinemia in Crigler-Najjar syndrome type-1(CNS-1) , a model for inherited metabolic liver disorders.
Gene therapy
Unconjugated hyperbilirubinemia in Crigler-Najjars syndrome caused by deficiency for UGT1A1, a liver enzyme that catalyses the conjugation of bilirubin, an essential step for efficient biliary excretion. Liver transplantation is the only curative option for the severe form of this disease. In view of the lack of donor organs, the very invasive treatment and the adverse effects of longterm immune suppression needed to prevent organ rejection, gene therapy seems a preferable option. Proof of concept for this approach in both relevant animals models for this disease was obtained. In close collaboration with an european consortium, CURECN, consisting out of patient groups from several european countries, clinical centers treating CN patients and GENETHON, all additional preclinical work for a small scale clinical study was completed. A clinical gene therapy trial to treat this severe disorders has started in 2018. Addition studies are focussed on rapid registration upon cmpletionof the trial. In addition to CN the applicability of gene therapy for other inherited severe liver disorders like Progressive Familial Cholestasis is investigated.
Liver function and bile transport.
In vivo knock-down using AAV mediated expression of sh constructs is used to reduce the expression of liver speicfic transporters to clarify their role in liver function and especially in bile formation. Efficient knock down of for instance P4 type ATPases is used to clarify their role in biliary transport and in vesicle production.
Themes: Gastro-intestinal diseases and Metabolic Disorders
- Europese Unie