Two MPAN project grants totaling $140,000 awarded

from | December 22, 2022

Hoffnungsbaum e.V. in conjunction with three sister organizations in Europe and the US, has awarded two MPAN grants to advance research priorities in the field of mitochondrial membrane protein-associated neurodegeneration (MPAN), which were identified during an expert workshop on MPAN. MPAN is one of the four most common types of the disease group whose generic term is "neurodegeneration with iron storage in the brain".

Dr. Lena F. Burbulla from the Ludwig-Maximilians-Universität in Munich and Dr. Rajnish Bharadwaj from the University of Rochester in New Jersey (USA) each received one-year research grants of $ 70,000 to study MPAN.

The funding was made possible by an international collaboration involving Hoffnungsbaum e.V. NBIA Disorders Association in the USA, Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) in Italy and Stichting Ijzersterk in the Netherlands.

In a workshop at the end of 2020 led by Dr. Francesca Sofia, founder and CEO of Science Compass in Milan, Italy, the researchers jointly discussed a research strategy for MPAN based on existing research data and assessed strengths, challenges and trends in MPAN research to identify a set of scientific priorities. Details can be found here:


Dr. Lena F. Burbulla from the Ludwig-Maximilians-Universität in Munich

Mitochondria, dopamine metabolism and alpha-synuclein

Burbulla's research involves modeling human disease by creating patient-derived cells to discover new mechanisms underlying the pathology of MPAN. To this end, her lab is using induced pluripotent stem cells (iPSCs) derived from skin cells of people with MPAN. Burbulla's team will use these stem cells - which can theoretically be turned into any type of cell in the body - to generate dopaminergic nerve cells, known as neurons, which are known to be affected in the brains of MPAN patients. Dopaminergic neurons produce the neurotransmitter dopamine, a chemical messenger involved in the regulation of body movement, memory, motivation, attention, learning and more.

Mutations in a specific gene, C19orf12, are the only known cause of MPAN. The function of the C19orf12 protein, which is controlled by the gene, is still largely unknown. Using disease modeling approaches, the researchers will investigate the function of the C19orf12 protein in a patient-specific model, in particular how the loss of this protein affects the brain cells. Burbulla and her team want to find out how the loss of C19orf12 function affects the health of the mitochondria in these patients' nerve cells. Mitochondria are the "powerhouses of the cell", producing around 90% of the energy cells need to survive. When mitochondria are damaged, this can have catastrophic consequences for the cell, triggering a series of toxic events that ultimately lead to neuronal death. Since the C19orf12 protein is known to be associated with mitochondria, its loss of function could affect mitochondria and have far-reaching effects on cell health and resilience.

The stem cell model will allow the researchers to compare the MPAN cells with healthy cells and better understand the role of the protein. They will also look beyond the mitochondria for disease-related pathology and investigate possible changes in the processing of the neurotransmitter dopamine in these nerve cells, as well as a protein called alpha-synuclein, which is known to accumulate pathologically in the brains of MPAN patients.

Alpha-synuclein is found at the ends of nerve cells in the synaptic cleft - the area between neurons where neurotransmitters are released to relay messages throughout the body. Abnormally formed or excessively abundant alpha-synuclein leads to aggregation or clumping of proteins and inhibits the normal function of neurons.


Dr. Rajnish Bharadwaj from the University of Rochester in New Jersey (USA)

Knockout flies, lipid metabolism and mitochondrial function

Baharadwaj's research will focus on better understanding the proteins produced by the C19orf12 gene. His team will use models of fruit flies that have been genetically engineered to lack the genes CG3740 and CG11671, which correspond to the C19orf12 gene in humans.

Previous studies by other groups and his ongoing work have shown that the fly models have a shorter life expectancy, movement deficits and a loss of neurons in the brain and retina. This suggests that fruit flies are a promising model for the study of NBIA.

The team's studies also suggest that C19orf12 is a membrane contact site protein that may be involved in communication between organelles, specialized subunits within the cell, such as the endoplasmic reticulum, and lipid droplets (fats). In the cell, the endoplasmic reticulum has the task of producing proteins and is involved in the production and storage of lipids.

The team's aim is to investigate how the C19orf12 protein is involved in lipid metabolism and mitochondrial function. Lipid metabolism is the process of production and breakdown of lipids or fats in cells. The researchers want to uncover this role in the brain and other organs. Both lipid metabolism and mitochondrial function are also involved in other forms of NBIA.

Overall, the creation and study of these disease models and the research that builds on them will improve the understanding of MPAN and pave the way for the much-needed development of treatments.


Source: Article "Two MPAN grants worth $140,000 awarded to further disease insights" in the December 2022 newsletter of the NBIA Disorders Association. Thank you for your kind permission to use the content of the article. Translations with the help of the free version of

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