Current call for an MPAN grant reflects clearly defined priorities

Hoffnungsbaum e.V. is collaborating with three sister organizations on a current call for grants of up to $145,000 for one two-year or two one-year MPAN research projects: https://www.hoffnungsbaum.de/call-for-proposals-on-mpan-research-2022/

The joint campaign is financially supported by our German NBIA patient organization Hoffnungsbaum e.V. as well as financially supported by AISNAF (Italy), NBIA Disorders Association (USA) and Stichting Ijzersterk (Netherlands). We invite researchers to submit their proposals to study mitochondria-membrane protein-associated neurodegeneration (MPAN), with the goal of awarding funding by summer 2022.

The MPAN project funding announcement is the result of a coordinated process to identify research priorities for this not-so-rare NBIA variant, which accounts for approximately 5%-10% of all NBIA disorders. MPAN, caused by mutations in the C19orf12 gene, is characterized by gait changes followed by progressive spastic paralysis, dystonia, neuropathic disorders, problems with speech and swallowing, optic nerve degeneration, neuropsychiatric abnormalities, and progressive cognitive impairment.

Analysis of the MPAN research landscape to identify a targeted research strategy.

Discovered in 2011, the function and role of this gene in the disease process are still largely unknown, although MPAN has been studied in several research projects, funded by the NBIA patient organizations in the USA, Switzerland, Poland and Germany, among others. The 2020-ongoing project funded by Hoffnungsbaum e.V. funded MPAN project is still ongoing and will hopefully be able to solve some of the open questions soon. However, this will not be enough. Further projects are urgently needed to help the so far rather rudimentary and underfunded MPAN research to breakthrough to effective treatments.

After receiving no viable MPAN project proposals in 2018 and 2019 calls for proposals. Hoffnungsbaum e.V., AISNAF and the NBIA Disorders Association saw the need for a comprehensive analysis of the global MPAN research landscape to date as a starting point for new projects. Thus, we commissioned Science Compass, led by Dr. Francesca Sofia, to conduct this research analysis.

This included a thorough review of the scientific literature on MPAN, NBIA, and related disorders, as well as information on publicly available institutional websites and databases. Several researchers with extensive experience in the field of NBIA disorders then expressed their assessments of MPAN research in interviews between June and July 2020. The resulting document served as the basis for discussions held during a two-day virtual expert workshop in October 2020 to design a collaborative strategy to fill the knowledge gaps that impede the development of effective treatments for MPAN.

Workshop defines MPAN research priorities.

Workshop participants, including basic scientists and clinicians and accompanying representatives from patient organizations, identified and prioritized two main goals for MPAN research in particular, with the aim of developing new MPAN-specific therapies.

• The first priority is to support basic research for new breakthrough insights into the C19orf12 gene, its disease-causing mutations, and the protein associated with it.
• The second priority is the development of new model organisms or the in-depth investigation of existing models in order to better understand the disease characteristics. Animal models as well as human cell models, e.g. obtained from skin cells of patients, come into question. It is also important here to identify the specific cell types that are affected by gene mutations.

Basic research is key to gaining new insights into the molecular and cellular functions of C19ORF12, which may then lead to new root-cause therapeutic interventions in MPAN that do not yet exist.

Theoretically, gene therapy is promising, but at this stage it is only a concept because essential basic science information on MPAN is lacking. Further research may reveal the utility of other drugs, including those already used for other diseases.

Overall, the research strategy consensus underscores the need for translational research that brings together scientists, clinicians, and patients and more quickly translates basic research into practical applications for patients, a priority identified in the strategic planning process.

We patient organizations are confident that knowledge about MPAN will grow and that there will then be help for MPAN families who have been waiting for years for a breakthrough in research and possible treatments.