Two MPAN project grants totaling $140,000 awarded

Two MPAN project grants totaling $140,000 awarded

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

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

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

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 evaluated strengths, challenges and trends in MPAN research to establish a set of scientific priorities. Details can be found here: https://www.hoffnungsbaum.de/aktuelle-ausschreibung-einer-mpan-foerderung/

 

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

Mitochondria, dopamine metabolism and alpha-synuclein

Burbulla's research involves modeling human disease by creating the patient's own cells to discover new mechanisms underlying the pathology of MPAN. To do this, her lab uses induced pluripotent stem cells (iPSCs) derived from skin cells from 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 create dopaminergic nerve cells called neurons, which are known to be affected in the brains of MPAN patients. Dopaminergic nerve cells produce the neurotransmitter dopamine, a chemical messenger involved in regulating body movements, memory, motivation, attention, learning, and more.

Mutations in a particular gene, C19orf12, are the only known cause of MPAN. The function of the gene-controlled protein C19orf12 is still largely unknown. Using disease modelling approaches, the researchers will use a patient-specific model to investigate the function of the C19orf12 protein, in particular how the loss of this protein affects 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" that produce about 90% of the energy cells need to survive. When mitochondria are damaged, it can have catastrophic consequences for the cell, triggering a series of toxic events that eventually lead to the death of the nerve cells. 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 study 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 pathologically accumulate in the brains of MPAN patients.

Alpha-synuclein is located 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 shaped 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 Flying, 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 CG3740 and CG11671 genes, 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 the fruit flies are a promising model for studying NBIA.

The team's studies also suggest that C19orf12 is a membrane junction 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 is responsible for producing proteins and is involved in the production and storage of lipids.

The team's goal is to investigate how the C19orf12 protein is involved in lipid metabolism and mitochondrial function. Lipid metabolism is the process of producing and breaking down 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 based 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 NBIA Disorders Association's December 2022 newsletter. We thank you for your kind permission to use the content of the article. Translations using the free version of https://www.deepl.com/translator

Current call for MPAN funding reflects clearly defined priorities

Current call for MPAN funding reflects clearly defined priorities

Hoffnungsbaum e. V. Logo
NBIA DA

Hoffnungsbaum e.V. is cooperating with three sister organizations in a current call for funding of up to USD 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 AISNAF (Italy), NBIA Disorders Association (USA) and Stichting Ijzersterk (Netherlands). We invite researchers to submit their proposals to study Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN), with the aim of awarding funding by summer 2022.

The announcement of MPAN project funding 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 determine 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 investigated in several research projects funded by the NBIA patient organizations in the USA, Switzerland, Poland and Germany, among others. The MPAN project, which has been Hoffnungsbaum e.V. funded MPAN project is still ongoing and will hopefully be able to solve some of the open questions soon. But it will not be enough. Further projects are urgently needed to help MPAN research, which has so far been rather rudimentary and underfunded, achieve a breakthrough in effective treatments.

After not receiving any viable project proposals for MPAN in the 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. 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 many years of experience in the field of NBIA diseases then gave their assessments of MPAN research in interviews between June and July 2020. The resulting document served as the basis for discussions that took place during a two-day virtual expert workshop in October 2020 to design a joint strategy to close the knowledge gaps that hinder the development of effective treatments for MPAN.

Workshop defines MPAN research priorities

The workshop participants, including basic researchers and clinicians as well as accompanying representatives of 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, groundbreaking findings on the C19orf12 gene, its disease-causing mutations and the associated protein.
  • The second priority is the development of new model organisms or the in-depth investigation of existing models in order to better understand the characteristics of the disease. Both animal models and human cell models, e.g. obtained from patients' skin cells, are being considered. It is also important to determine the specific cell types that are affected by gene mutations.

Basic research is the key to gaining new insights into the molecular and cellular functions of C19ORF12, which can then lead to new therapeutic interventions for MPAN that address the root causes, which do not yet exist.

Theoretically, gene therapy is promising, but at this stage it is only a concept, as essential basic science information on MPAN is lacking. Further research could reveal the benefits of other drugs, including those already in use for other diseases.

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

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

Call for proposals on MPAN research open by May 2, 2022

Call for proposals on MPAN research open by May 2, 2022

Hoffnungsbaum e. V. Logo
NBIA DA

Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF, Italy), Hoffnungsbaum e.V. (HoBa, Germany), NBIA Disorders Association (NBIADA, USA), and Stichting Ijzersterk (The Netherlands) are soliciting the submission of research projects by investigators committed to advancing the understanding of Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN) in order to pave the way to targeted treatments.

MPAN is caused by mutations of the gene C19Orf12 and manifests as one of the more frequent subtypes within the group of NBIA (Neurodegeneration with Brain Iron Accumulation) Disorders. For an overview see: https://www.ncbi.nlm.nih.gov/books/NBK185329/

More specifically, the four associations are interested in funding studies to:
• uncover the structural and/or functional properties of C19Orf12 protein,
• reveal the functional and molecular effects of various genetic mutations underlying MPAN,
• develop new disease models or study existing ones to shed light on mechanisms.

Budget:
Funds are made available through contributions by all four organizations in the overall amount of USD 145,000. The following types of grant applications may be submitted:
• up to USD 70,000 for a one-year project,
• up to USD 145,000 for a two-year project.

Applicants may submit a grant application for either one or two years or both to allow flexibility and consider the different needs of researchers. Multiple grants may be awarded if two one-year grants are considered most worthy of funding.

Call documents with detailed information are available here: https://cloud.hoffnungsbaum.de/s/zw3r75pb5KZa7Lc and they include:    
• Request for Proposals / Proposal guidelines MPAN 2022
• Draft grant agreement MPAN 2022
• Templates, to be submitted in one PDF file: cover letter, PI bio, main proposal

Deadline for proposal submission: May 2, 2022, 24:00 CEST

Applicants may contact the grant manager at grantmanager@sciencecompass.it  for further information and clarification.

NBIA Disorders Association family conference sessions now available online

NBIA Disorders Association family conference sessions now available online

The virtual conference platform is now open to all, free of charge, so that interested English-speaking families can view those sessions that are available as recordings. The program includes patient-focused research updates and information from NBIA specialists at Oregon Health & Science University in Portland (USA) and other NBIA scientists on clinically relevant questions for the most common NBIA forms PKAN, BPAN, MPAN, PLAN and FAHN. In addition, there are cross-variant sessions on special topics such as dental health and nutritional problems, as well as tips for fundraising and public relations.

This and much more can be found under this link: https://nbiaconference.org/ In order to access the lectures, you have to register for free beforehand.

The NBIA Disorders Association is also celebrating its 25th anniversary in September. We would like to take this opportunity to congratulate our big sister organization on this anniversary, without whose encouraging example there would probably not be many NBIA associations in the world. Also Hoffnungsbaum e.V. also owes a great deal to the NBIA Disorders Association and its extremely dedicated chairperson Patricia Wood (Founding history). We wish this beacon of the NBIA patient movement much continued success and radiance.

Record number of participants at the 7th International Scientific NBIA Symposium

Record number of participants at the 7th International Scientific NBIA Symposium

Autoren des englischen Originalartikels: Patricia Wood und Angelika Klucken

160 Teilnehmer aus 26 Ländern besuchten das 7. Internationale Symposium zu NBIA und verwandten Erkrankungen, das erstmals als virtuelle Veranstaltung stattfand. Da der online-Zugang es erleichterte, sich während der COVID-19-Pandemie im virtuellen Raum zu treffen, wurde diese Rekordanzahl an Teilnehmern ermöglicht, zu denen die weltweit renommiertesten NBIA-Wissenschaftler und -Kliniker gehörten sowie diejenigen Fachleute, die sich erst seit kurzem mit NBIA-Forschung und -Versorgung befassen.

Den Vorsitz im Wissenschaftlichen Lenkungsausschuss des Symposiums hatte Prof. Thomas Klopstock, Leiter des NBIA-Forschungsteams am Friedrich-Baur-Institut der Neurologischen Universitätsklinik München (LMU). Dem Vorbereitungskomitee gehörten ferner Prof. Susan Hayflick von der Oregon Health & Science University in Portland, USA, Prof. Valeria Tiranti vom Neurologischen Institut C. Besta in Mailand, Italien, und Dr. Agnès Rötig vom Institut Imagine in Paris, Frankreich, an. Die Patientenvertreterinnen Fatemeh Mollet von NBIA Suisse, Angelika Klucken von Hoffnungsbaum e. V. und Patricia Wood von der NBIA Disorders Association in den USA waren ebenfalls Ausschussmitglieder.

Das Bild zeigt die virtuelle Lobby des Symposiums. Teilnehmer konnten die Meetings oder Angebote anklicken, die sie wahrnehmen wollten.

 

Auf dem Programm der Tagung, die von der NBIA Disorders Association in den USA ausgerichtet wurde, standen Vorträge, in denen langjährige, erfahrene NBIA-Forscher und ihre Mitarbeiter*innen, über aktuelle Forschungsergebnisse berichteten. Darüber hinaus teilten Forscher, die neu in der NBIA-Gemeinschaft sind, jedoch über besonderes Fachwissen zu modernsten Therapieverfahren verfügen, ihre Kenntnisse und trugen zum Gedankenaustausch bei.

Das Sitzungsprogramm konzentrierte sich jeden Tag insbesondere auf ein oder zwei der häufigeren NBIA-Erkrankungen – PKAN, CoPAN, BPAN, MPAN, PLAN und FAHN, aber die Diskussionen über einzelne Erkrankungen waren für alle NBIA-Formen von übergreifendem Interesse. Insgesamt kristallisierten sich fünf krankheitsübergreifende Themen als Diskussionsschwerpunkte heraus:

  • Entzifferung der pathologischen biochemischen Mechanismen der Krankheiten und damit Gewinnung neuer Ideen für mögliche neue Therapien
  • Erkundung des Potenzials von Gen-, niedermolekularen Arzneimittel- und Zell-Therapien bei der Behandlung von NBIA-Erkrankungen
  • Generierung geeigneter Tiermodelle und differenzierter Zellmodelle für vorklinische Tests
  • Durchführung von Studien zu den natürlichen Krankheitsverläufen und Entwicklung geeigneter subtypspezifischer Bewertungsskalen als Voraussetzung für klinische Studien
  • Durchführung klinischer Studien, die bevorstehen oder bereits laufen, und Anforderungen an deren Umsetzung.

Alle waren sich einig, dass eine ausreichende Finanzierung ein großes Hindernis bleibt, wenn es um die verschiedenen wissenschaftlichen Ansätze geht, die noch erforscht werden müssen. Ungeachtet des für eine Behandlung gewählten therapeutischen Ansatzes teilten die Forscher die Ansicht, dass parallel zu anderen Forschungsarbeiten die Studien zu den natürlichen Krankheitsverläufen (Engl: Natural History) nicht früh genug beginnen können, um aussagekräftige klinische Endpunkte zur Hand zu haben, mit denen man gut vorbereitet ist für klinische Studien, also so genannte Trial Readiness erzielt.
Patientenvertreter von 10 NBIA-Alliance-Mitgliedsorganisationen nahmen an der Konferenz teil, außerdem Vertreter der sieben Organisationen, die sich einer bestimmten NBIA-Erkrankung widmen. Biotech- und Pharmaunternehmen waren ebenfalls vertreten.

Die Teilnehmer hörten 37 wissenschaftliche Vorträge und sechs Blitzvorträge und konnten nach jeder Präsentation den Sprechern Fragen stellen. Darüber hinaus wurde jeder Tag mit dem Willkommensgruß eines Patientenvertreters eröffnet, der aus Patientenperspektive das Engagement der wissenschaftlichen NBIA-Gemeinschaft würdigte und ermutigte.
Jeder Tag endete mit einer lebhaften, für alle Teilnehmer offenen Diskussion über dringende Erfordernisse und nächste Schritte zu den in den Präsentationen behandelten NBIA-Krankheitsformen. An diesen Gesprächsrunden nahmen zwischen 50 und 75 Personen teil. Während des Symposiums wurden auch weitere Vernetzungsmöglichkeiten und virtuelle Ausstellungsstände angeboten.

Susan Hayflick, medizinische Genetikerin und Leiterin der NBIA-Forschung in Portland, Oregon (USA), schlug vor, dass sich die Forscher zusätzlich zu den persönlichen Symposien häufiger virtuell treffen sollten, um den wissenschaftlichen Austausch zu verbessern und die NBIA-Forschung zu beschleunigen. Viele stimmten dem zu und bewerteten die Qualität der auf dem Symposium verwendeten virtuellen Plattform als sehr gut.

Die meisten der Vorträge wurden aufgezeichnet und sind jetzt unter folgendem Link verfügbar:

https://NBIAscientificsymposium.org

Für Laien verständliche Zusammenfassungen der täglichen Vorträge sind in Arbeit und können demnächst von den gemeinnützigen NBIA-Patientenorganisationen zur Verfügung gestellt werden. Im Jahr 2021 wird das 8. Internationale Symposium zu NBIA und verwandten Erkrankungen vom 14. bis 16. Oktober 2021 als persönliches Treffen in Lausanne, Schweiz, stattfinden.

DieseÜbersetzung wurde durch www.DeepL.com/Translator (free version) is supported.

Hoffnungsbaum e.V. finances MPAN project at Helmholtz Zentrum München

Hoffnungsbaum e.V. finances MPAN project at Helmholtz Zentrum München

Hoffnungsbaum e.V. awards funding in the amount of € 151,540 to Dr. Arcangela Iuso and her team from the Institute of Neurogenomics at the Helmholtz Center in Munich. The funding will finance a 27-month research project to uncover key disease mechanisms in MPAN (mitochondrial 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 C19orf12 gene in the lipid metabolism of cells.

MPAN is one of the four most common subtypes in the group of diseases summarized as neurodegeneration with brain iron accumulation (NBIA). This form of NBIA leads to progressive movement disorders and often to neuropsychiatric symptoms and impaired vision. MPAN predominantly begins in later childhood and inevitably leads to severe disabilities. 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. If these cellular processes are disrupted, this can lead to an abnormal accumulation of metabolic products such as lipids or iron.

From left to right: PhD student Enrica Zanuttigh, cooperation partners Drs. Lucia Berti, Ben Engel, Sophie Ayciriex (not pictured), project leader Dr. Arcangela Iuso, junior scientist Dr. Tilak Kumar Gupta, and technical assistant Annett Hering are working together to investigate the role of C19orf12 in the lipid metabolism of cells.

"With the proposed project, we want to investigate the function of the C19orf12 protein as a potential link between membranes within the cell and fully elucidate the effects of mutations in the C19orf12 gene on cellular processes that are mainly related to lipid metabolism," Iuso explains her project.
It would be an important milestone for MPAN and NBIA research to finally decipher the cellular function of the C19orf12 protein. As there are overlaps in the underlying molecular mechanisms of many NBIA diseases, this project could also provide insights into other forms of NBIA.
Iuso and her team will work with Dr. Benjamin Engel's laboratory on the Helmholtz Pioneer Campus to use a cutting-edge technology, cryo-electron tomography. This technique produces three-dimensional images of cells with fine molecular details. By directly imaging proteins that are in action in the natural cellular environment, cryo-electron tomography provides molecular insights into cellular processes and thus also into disease mechanisms. The groups of Iuso and Engel 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 for Diabetes Research and Metabolic Diseases at the Helmholtz Zentrum München at the University of Tübingen.
"If we succeed in elucidating the function of C19orf12 in the context of lipid metabolism," says Iuso, "this will hopefully pave the way for the development of an effective treatment for MPAN based on the disease mechanisms."

The financing of this research project was made possible by numerous fundraising campaigns and individual donations. Thanks to the private initiative of a family whose daughter was diagnosed with MPAN in 2018 and their many supporters, particularly in Saarland, an important research project has been launched to shed light on the mechanisms of the disease and pave the way for therapies. On behalf of Maya and all children, adolescents and adults affected by MPAN around the world, we would like to take this opportunity to thank all our supporters once again for their overwhelming willingness to donate. The fundraising campaign will continue for the benefit of other MPAN projects: Help Maya

The Helmholtz Center Munich is a research center with the mission of developing personalized medical solutions for the prevention and treatment of environmental diseases for a healthier society in a rapidly changing world. The center is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München employs around 2,500 people and is a member of the Helmholtz Association, the largest scientific organization in Germany with more than 40,000 employees in 19 research centers.

On Institute for Neurogenomics (ING) focuses on the genetic basis of neurological diseases. Research focuses on the underlying genomic architecture and the molecular mechanisms of complex genetic and rare neurological diseases. The aim is to research 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.

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