Project: Translating Peroxisome Biogenesis Disorders: Identifying Pharmacological Therapies and Clinical Trial Endpoints

Peroxisome biogenesis disorders (PBD) are rare autosomal recessive disorders caused by defects in any one of 14 PEX genes whose protein products are required for peroxisome assembly. Defective peroxisome assembly results in multiple peroxisomal enzyme deficiencies and multi-organ failure over life span. The majority of patients have PEX gene defects that retain residual PEX protein functions, and thus should be amenable to drug therapies that can enhance residual function or mitigate downstream metabolic defects. Importantly, there is a window to intervene in PBD and prevent or ameliorate disease progression. Currently there is no treatment for PBD. In pilot studies, we identified chaperone drugs that can recover peroxisome functions in patient cell lines. We have also identified drugs that increase peroxisome numbers and correct affected downstream signaling pathways. We have shown that plasmalogens, a critical missing compound, can be replaced in somatic tissues by supplementation. Thus, we hypothesize that pharmacological therapies, based on manipulating the affected molecular and metabolic pathways, have valid potential to benefit PBD patients. In this project we will utilize our complementary resources and expertise to focus on identifying drug therapies that can recover peroxisome functions in our model systems. With our clinical expertise, we will mine our patient databases to determine rational endpoints for human trials. The completion of this project will lay solid groundwork for industry to optimize these therapeutic approaches for future clinical trials.

Acronym PERescue
Duration 01/01/2016 - 01/12/2018
Network E-Rare-3
Call E-Rare-3 JTC 2015

Project partner

Number Name Role Country
1 The Research Institute of the McGill University health Center Observer Canada
2 Academic Medical Center at the University of Amsterdam Partner Netherlands
3 Academic Medical Center at the University of Amsterdam Partner Netherlands
4 Medical University of Vienna Partner Austria
5 KU Leuven, Campus Partner Belgium
6 Instituto de Biologia Molecular e Celular – IBMC Partner Portugal