Survey helps prepare clinical trial for PKAN patients

Survey helps prepare clinical trial for PKAN patients

The Californian company CoA Therapeutics is currently preparing a clinical trial with a new drug for PKAN patients. In order to make this study as patient-oriented as possible, CoA Therapeutics developed a survey last year in which PKAN patients and their families could make their voices heard. The company actively involved representatives of the international NBIA patient organizations in the preparations. Two representatives from Hoffnungsbaum e.V. based on their own experience as parents of PKAN children and as long-standing patient representatives, helped to prepare the survey in the best possible way and to make it known to the families. We are therefore very pleased that CoA Therapeutics is now presenting the survey results and would like to share this summary with you:

 

Summary of CoA Therapeutics' survey for people with PKAN

The team at CoA Therapeutics would like to thank the individuals and families affected by PKAN for their participation in the recent survey. We were very impressed by the level of community engagement with 183 responses received. We would especially like to thank our partners in patient organizations who commented on the survey and helped to disseminate it.

Key findings from the survey included information on the timing of disease onset in people with PKAN: half of respondents said that the first PKAN-related symptoms appeared before the age of 10, more than a third experienced the first symptoms at the age of 10 or later, and ten percent were not sure when the first symptoms appeared. Respondents came from many countries, most from Poland (21%), the Dominican Republic (18%), the USA (15%), Italy (9%), Spain (7%) and Germany (6%). Responses from affected families also came from 17 other countries, including France, Brazil, Canada, Cuba, Egypt, India, Iran, Jordan, Mexico, the Netherlands, New Zealand, Norway, Saudi Arabia, Slovenia, Switzerland, Ukraine and the United Kingdom.

The majority of people with PKAN reported being diagnosed before the age of 12 (59%), and most had a genetic test to confirm their PKAN diagnosis (81%). Respondents most commonly reported that problems with balance/falls, motor skills and muscles were the first PKAN symptoms they experienced.
The majority of respondents stated that they were taking several medications, with anticonvulsants, skeletal muscle relaxants and antipsychotics being mentioned most frequently. Only 22 people stated that they were not taking any medication. Approximately 1 in 4 respondents reported having a deep brain stimulation (DBS) device implanted and a similar proportion reported having a feeding tube.
When asked about the most difficult medical examinations, respondents stated that imaging procedures (e.g. X-ray, MRI, CT scans) were the most difficult, as they could not maintain the required posture, were tense and required sedation.
In an open-ended question about the top three symptoms that are most difficult/challenging for people with PKAN, dystonia (86 mentions), impact on speech (83 mentions) and difficulty eating (64 mentions) were most frequently mentioned. When asked to name the three most important symptoms that could hopefully be improved by a new treatment, the most frequently mentioned were effects on speech (87 mentions), dystonia (70 mentions) and difficulty eating and walking (47 mentions each).
About half of respondents reported having participated in a clinical trial in the past, and these individuals reported that travel and visits were the most difficult aspects of trial participation. Also, the most frequently cited ways to improve clinical trial participation were less travel/visits and better on-site visit experiences, such as more support at the clinical center, more comfortable admission conditions, and a place to rest.
Thank you again for your participation in our survey. Your experiences are invaluable to our work and directly help us as we work to develop a therapy for PKAN. As next steps, we are preparing a more detailed presentation to share with the community later this year. We at CoA Therapeutics are also committed to sharing these research findings with a broader audience to inform other scientists, clinicians and companies working to develop therapies for PKAN.

Translation from English with the support of https://www.deepl.com/translator, free version

Current call for MPAN funding reflects clearly defined priorities

Current call for MPAN funding reflects clearly defined priorities

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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

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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.

Generational change in the Management Board of Hoffnungsbaum

Generational change in the Management Board of Hoffnungsbaum

Am 21.11.2021 fand die jährliche Mitgliederversammlung von Hoffnungsbaum e.V. (HoBa) statt – mit wegweisenden Entscheidungen für die Zukunft unserer NBIA-Patientenorganisation durch den Abschluss des Generationenwechsels in der Vereinsführung und die Umorganisation der zukünftigen Vorstandsarbeit. Im geschäftsführenden Vorstand hat Markus Nielbock nun den Vorstandsvorsitz übernommen, Sebastian Matthiesen wurde Zweiter Vorsitzender und Sigune Lüchtefeld ist neue Schatzmeisterin. Anja Barthe, Noah Rusch und Tiemo Durm wurden wiedergewählt und Ufuk Calisici kommt als neue Unterstützung hinzu. Weitere Informationen zum aktuellen Vorstand finden Sie unter: https://www.hoffnungsbaum.de/verein/vorstand/

Mein Mann Stephan und ich bleiben nach unserem Rückzug aus dem aktiven Vorstand nach 19 Jahren verantwortlicher Tätigkeit für Hoffnungsbaum e.V. der neuen Vereinsführung noch eine Zeit lang in beratender und unterstützender Funktion eng verbunden.

Wir möchten uns hiermit bei allen NBIA-Familien, Vereinsmitgliedern, Ärzten und Forschern, bei den Partnern aus der NBIA-Selbsthilfe, unseren Dachverbänden sowie den unterstützenden Krankenkassen und den vielen Spendern für das über viele Jahre hinweg entgegengebrachte Vertrauen und für die gute Zusammenarbeit sehr herzlich bedanken. Wir verabschieden uns von der aktiven Arbeit für Hoffnungsbaum e.V. etwas wehmütig, aber auch froh über die dringend nötige Entlastung, mit einem Zitat zur Hoffnung, die stets der Motor unserer Wirkens und unseres Lebens war und bleiben wird:

 

„Hoffnung ist eine große Macht, vielleicht die größte von allen… Im Hoffen liegen Kraft zum Weitermachen, zum Nichtaufgeben, und Hoffnung wird nicht verstanden als Herumsitzen und Abwarten, bis das Richtige sich irgendwie einstellt, sondern sie ‚verlangt Menschen, die sich ins Werdende tätig hineinwerfen‘ (Ernst Bloch)“ Gesamtzitat aus: Der Spiegel 14/2021 – Essay von Ullrich Fichtner

Der Führungswechsel in unserer NBIA-Patientenorganisation ist das Ergebnis einer systematischen Vorbereitung. Am Anfang stand ein gemeinsames Abendessen mit engagierten Neu-Mitgliedern anlässlich der Mitgliederversammlung 2017 in Düsseldorf. Gast-Teilnahmen an unseren virtuellen Vorstandssitzungen halfen dann den „Neuen“ dabei, allmählich die umfangreiche Vorstandsarbeit von Hoffnungsbaum schon vor der Übernahme von Verantwortung kennenzulernen und auch eigene Ideen dafür zu entwickeln. Seit der Familienkonferenz 2018 konnten so schrittweise Vorstandspositionen, die frei wurden, neu besetzt werden. Geholfen haben bei dieser sanften Übergabe der Verantwortung auch zwei ganztägige Strategiesitzungen 2019 und 2021, die der Vorstand mit Interessent*innen an der Vorstandsarbeit dank der Unterstützung durch die DAK Gesundheit durchführen konnte.

Eine weitere wesentliche Veränderung betrifft die Neuorganisation der täglichen Vereinsarbeit in Form von Arbeitsgruppen (AGs), die jeweils einen Aufgabenbereich unserer Selbsthilfearbeit repräsentieren und selbständig bearbeiten. Jede der derzeit noch 6 AGs wird von einem Vorstandsmitglied verantwortlich geleitet: AG Betroffenenberatung , AG Familienkonferenzen, AG Forschungsförderung, AG Informationsverbreitung, AG Fundraising, AG Verwaltung

Zur Mitarbeit in den AGs ihres Interesses sind auch herzlich alle Vereinsmitglieder und Familien eingeladen, die sich für eine Vereinsmitgliedschaft interessieren. Hoffnungsbaum e.V. ist auf einem guten Weg in die Zukunft mit engagierter neuer Vereinsführung, die jede Unterstützung brauchen kann und verdient.

Wir haben alle dasselbe Ziel und arbeiten daran, ihm näherzukommen: Bessere medizinische Behandlungen für unsere Liebsten zu finden und verfügbar zu machen, um ihr Leben mit NBIA zu verbessern!

New BPAN mouse model from Munich now available for researchers

New BPAN mouse model from Munich now available for researchers

With the publication of a long-awaited paper on a BPAN mouse model, researchers around the world now have access to these mice for study.

Scientists led by Dr. Holger Prokisch from the Technical University of Munich have created a strain of mice by systemically inactivating or switching off the gene associated with beta-propeller protein-associated neurodegeneration (BPAN). BPAN is now considered the most common form of NBIA.

In the corresponding article by Dr. Arcangela Iuso (Helmholtz Zentrum München), the new mouse model is also comprehensively characterized. It is reported that from the age of four months, the mice showed increasing problems with the nervous system, accompanied by hearing and vision problems. In the mice, there was no iron accumulation in the brain.

However, specific biochemical changes suggest that in the absence of the autophagy gene WDR45, the mitochondria do not produce enough energy, preventing the affected cells from functioning properly. The thesis shows that the knock-out mouse model complements the three other BPAN mouse models previously described in the literature and compares the available mouse models with each other. The systemic BPAN mouse developed in Munich represents another robust model to test drugs against the disease and to study how BPAN affects the body's systems and causes functional changes with health consequences.

The paper, published in the journal Mammalian Genome, is titled "A comprehensive phenotypic characterization of a whole-body Wdr45 knock-out mouse." It is freely accessible in so-called "Open Access" and can be accessed at: https://pubmed.ncbi.nlm.nih.gov/34043061/

Researchers who wish to order the mice for study purposes can do so via a form provided by Helmholtz Zentrum München at: https://www.infrafrontier.eu/search?keyword=EM:13607 The website notes that there may be delays in the processing of orders due to the pandemic.

The development of the BPAN mouse can be traced back to a $67,760 grant of funding for the project from the NBIA Disorders Association Prokisch in 2015. However, personnel changes during the course of the project led to delays in the publication of the work and the deployment of the mouse strain. It is thanks to Dr. Ijo's tenacity in publishing and Dr. Prokisch's continued efforts that the mouse strain is now available to interested researchers.

 

Source: NBIA Disorders Association September 2021 newsletter
translated using the free version of https://www.deepl.com/translator and revised by Angelika Klucken

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