NBIA Poland funds study to better understand MPAN’s causes

April 2021

The association that represents all NBIA disorders in Poland has awarded a research grant for €59,000 ($71,571 U.S. dollars) to two researchers in a German Research Center who are investigating still-unanswered questions about the underlying causes of MPAN.

MPAN, which stands for mitochondrial membrane protein-associated neurodegeneration is caused by mutations of the C19orf12 gene.

Dr. Arcangela Iuso, researcher from Helmholtz Zentrum Munich.

The grant to Dr. Arcangela Iuso and Dr. Ana Messias from the Helmholtz Zentrum Munich is to help fund a two-year research project on MPAN that started in September 2020. Titled “Investigating C19orf12 functions in redox metabolism,” the goal is to better understand how the mutation affects individuals and what drugs might help MPAN patients.

Dr. Ana Messias, researcher from Helmholtz Zentrum Munich.

Preliminary studies have shown that when the gene C19orf12 is mutated, many processes in the cells are altered leading to MPAN, a progressive degenerative disease. In particular, cells from MPAN patients seem to have increased calcium compared to cells from healthy donors, and are more susceptible to oxidative stress, which occurs when the body has an excess of free radicals. This imbalance can lead to cell and tissue damage, which is part of what the researchers will study.

They also will use several molecular biology and biochemical methods to compare skin cells of MPAN patients to the cells of unaffected MPAN carriers (parents) and other healthy individuals. They want to see if there are significant differences between the cells of each group.
The researchers also will examine the proteins that are produced from the C19orf12 gene mutations. They will compare the normal protein found in healthy individuals to the mutated version that is found in individuals with MPAN.

The goal of comparing the healthy and MPAN cells and non-mutated proteins to the mutated ones is to find some differences that could be used to develop a therapeutic approach for MPAN. The researchers will then test different drugs that could reverse the cell damage in MPAN individuals. The team’s ultimate goal is to identify successful MPAN therapies.
Iuso and Messias will be collaborating and exchanging information with Drs. Marta Skowronska and Tomasz Kmiec, clinicians who see MPAN patients in Poland. Poland has the largest cohort of MPAN patients in the world, with over 45 individuals diagnosed to date.

NBIA Poland will support this project by facilitating scientific exchange between the Munich researchers and the Polish researchers and by making the MPAN patient community aware of the importance of donating biosamples for the research project.

Anyone interested in donating a biosample to the research group should contact Dr. Maciej Cwyl, President of NBIA Poland at mc@il.pw.edu.pl.