2023 Million Dollar Bike Ride Results in $120,000 for BPAN Research
March 2024
By Patricia Wood
The 10th annual Million Dollar Bike Ride (MDBR), hosted by the University of Pennsylvania’s Orphan Disease Center, resulted in two NBIA researchers each receiving a $60,000 grant to study Beta-Propeller Protein-Associated Neurodegeneration (BPAN).
NBIA Disorders Association has participated in this annual event, raising funds for research since 2018. In all, ten BPAN research grants have been awarded, totaling $590,714.
Our organization prepares the request for proposals and selects the grant reviewers. The University of Pennsylvania manages the grants and sends us copies of the scientific reports that grant recipients provide. They also provide $30,000 in matching funds for the first $30,000 raised. The current funding period runs from February 1, 2024 – January 31, 2025.
Our two grant recipients are Dr. Mario Mauthe from the University Medical Center Groningen, the Netherlands, and Dr. Manju Kurian from University College London, United Kingdom.
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| Dr. Mario Mauthe, University Medical Center Groningen, The Netherlands |
When mutated, the WDR45 gene codes for a protein called WDR45, which leads to BPAN. This protein is involved in autophagy, a process responsible for degrading and recycling damaged cellular components. The mutated WDR45 protein also affects cellular organelles called mitochondria, which play vital roles in energy production, metabolism regulation and immunity. Mitochondrial dysfunction is not unique to BPAN and is also observed in several other NBIA disorders, such as PKAN, CoPAN, PLAN and MPAN.
This project will investigate how mutations in WDR45 affect and interfere with mitochondria structure and function and how these alterations contribute to the BPAN pathophysiology. In particular, they will look at WDR45’s role in maintaining mitochondrial homeostasis and they will also identify potential drugs reversing mitochondrial dysfunction caused by WDR45 mutations.
To understand the role of WDR45 in mitochondrial dysfunction, Mauthe’s team will focus on studying the proteins involved in mitochondrial functions that are misregulated in WDR45 defective cells. For their investigations, they will use various cutting-edge research methods such as proteomic analyses, generation of induced neurons from patient fibroblasts, automated live cell imaging, and ultrastructural examination of mitochondria.
In addition, they aim to identify pharmaceutical compounds that can rescue mitochondrial dysfunctions observed in WDR45 defective cells. They will utilize an automated imaging system to evaluate drug effects on these cellular phenotypes.
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| Dr. Manju Kurian, University College London, United Kingdom |
Our other grant recipient, Kurian, is focusing on gene therapy for BPAN. Her group has experience working on gene therapy for PLA2G6-Associated Neurodegeneration (PLAN), another NBIA disorder, which Bloomsbury Genetic Therapies Limited is now moving forward.
The project proposes to develop gene therapy to deliver a healthy copy of the faulty BPAN gene directly into the brain. The aim is to establish a state-of-the-art laboratory model of disease (a ‘brain in a dish’) and use an excellent mouse model that shows key features of human disease to evaluate this gene therapy approach and see whether it rescues the problems caused by the faulty gene in BPAN.
A successful gene therapy study in their laboratory will allow them to accelerate a clinical gene therapy trial for children with BPAN. They hope gene therapy will halt disease progression, increase life expectancy, and provide a better quality of life for individuals and their families living with this condition.
We are grateful for the long-time support of Mauthe and Kurian and their dedication to NBIA research. These grants would not have been possible without the commitment of our community members who participate in fundraising for the Million Dollar Bike Ride each year. We also thank the Orphan Disease Center for their generous $30,000 match and their eagerness to fuel research for rare diseases.
