Hoffnungsbaum e.V. awards funding of € 151,540 to Dr. Arcangela Iuso and her team from the Institute of Neurogenomics at the Helmholtz Center in Munich. The grant will fund a 27-month research project to uncover key disease mechanisms in MPAN (mitochondria-membrane protein-associated neurodegeneration). Project leader Dr. Arcangela Iuso, an experienced MPAN researcher, and her team are investigating the role of the protein controlled by the gene C19orf12 in the lipid metabolism of cells.
MPAN is one of the four most common subtypes in the group of disorders collectively known as neurodegeneration with brain iron accumulation (NBIA). This form of NBIA leads to progressive movement disorders and often neuropsychiatric symptoms and impaired vision. MPAN predominantly begins in later childhood and inevitably leads to severe disability. There is still no therapy that could delay or stop this progression.
Mutations in the C19orf12 gene cause MPAN. They lead to an impairment of the corresponding protein function. Unfortunately, the exact function of this protein has not yet been deciphered. This is precisely where Dr. Iuso and her team are now starting. In their research project, they are investigating the hypothesis that the C19orf12 protein regulates both the lipid balance in the cell and the exchange of molecules between the intracellular organelles. When these cellular processes are disturbed, abnormal accumulation of metabolites such as lipids or iron can occur.
From left to right: PhD student Enrica Zanuttigh, cooperation partners Drs. Lucia Berti, Ben Engel, Sophie Ayciriex (not in picture), project leader Dr. Arcangela Iuso, junior scientist Dr. Tilak Kumar Gupta, and technical assistant Annett Hering work together to investigate the role of C19orf12 in cell lipid metabolism.
"With the proposed project, we aim to investigate the function of the C19orf12 protein as a potential link between membranes within the cell and to fully elucidate the effects of mutations in the C19orf12 gene on cellular processes mainly related to lipid metabolism," Iuso explains of her project.
It would be an important milestone for MPAN and NBIA research to finally decipher the cellular function of the C19orf12 protein. Since there is overlap in the underlying molecular mechanisms of many NBIA disorders, this project may well yield insights for other forms of NBIA.
Iuso and her team will collaborate with Dr. Benjamin Engel's lab at the Helmholtz Pioneer Campus to use a cutting-edge technology, cryo-electron tomography. This technique produces three-dimensional images of cells with fine molecular detail. By directly imaging proteins in action in the natural cellular environment, cryo-electron tomography provides molecular insights into cellular processes and, in turn, disease mechanisms. Iuso and Engel's groups will image cells from MPAN patients.
Other cooperation partners in the project are Dr. Sophie Ayciriex from the Institute of Analytical Sciences at the University of Lyon, and Dr. Lucia Berti from the Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen.
"If we can elucidate the function of C19orf12 in the context of lipid metabolism," says Iuso, "hopefully this will pave the way for the development of an effective treatment for MPAN based on disease mechanisms."
The funding of this research project was made possible by numerous fundraising campaigns and individual donations. Due to the private initiative of a family, whose daughter was diagnosed with MPAN in 2018, and their many supporters, especially in the Saarland, it was thus possible to start an important research project to shed light on the disease mechanisms in order to pave the way for therapies. On behalf of Maya and all children, adolescents and adults affected by MPAN in the world, we would like to take this opportunity to thank all supporters once again for their overwhelming willingness to donate. The fundraising campaign will be continued for the benefit of further MPAN projects: Help Maya
The Helmholtz Center Munich as a research center, pursues the mission of developing personalized medical solutions for the prevention and therapy of environmentally related diseases for a healthier society in a rapidly changing world. The center's headquarters are located in Neuherberg in the north of Munich. Helmholtz Zentrum München employs about 2,500 people and is a member of the Helmholtz Association, Germany's largest scientific organization with more than 40,000 employees in 19 research centers.
At Institute for Neurogenomics (ING) focuses on the genetic basis of neurological diseases. Research focuses on the underlying genomic architecture and molecular mechanisms of complex genetic and rare neurological diseases. The aim is to investigate the genetic basis of neurological diseases in order to improve their diagnosis and to be able to offer patients a customized individual therapy in the long term.