NBIA NEWS & INFORMATION

$60,000 Grant Awarded to study decreased Mitochondrial Energy Production in BPAN

December 2023

Dr. Arcangela Iuso from the Helmholtz Zentrum München’s Institute of Neurogenomics in Munich, Germany, has been awarded a one-year grant of $60,000 from our organization. Her project was selected from seven applications submitted for our BPAN grant call this past spring.

Arcangela Iuso, from the Helmholtz Zentrum München’s Institute of Neurogenomics in Munich, Germany.

Iuso’s project focuses on understanding why mutations in the WDR45 gene lead to reduced energy production by mitochondria, considered the powerhouses of the cells. This defect was initially pinpointed in the brain tissue of a BPAN mouse model. It appeared to be linked to the malfunctioning of a specific mitochondrial enzyme known as Respiratory Chain Complex I (RCCI), a discovery that Iuso co-authored in a 2021 publication available here.

Recently, the defect of RCCI was also identified in muscle and skin cells of a BPAN patient with the findings presented by Dr. Anna Ardissonne at the 8th International NBIA Symposium held last October in Lausanne, Switzerland.

Iuso's current project aims to clarify if the enzymatic issue affects all brain cells uniformly or if specific cell populations, such as neurons or their supporting cells, are more susceptible. To investigate this, Iuso's laboratory will generate neurons and supportive cells using induced pluripotent stem cells (iPSCs) derived from the skin cells of individuals affected by BPAN. This methodology will help pinpoint the precise brain cell type the enzymatic deficiency impacts.

The subsequent phase involves exploring therapeutic compounds that could potentially restore the enzymatic activity of RCCI within the laboratory setting. Iuso aims to evaluate natural compounds or FDA-approved molecules in the hopes of identifying a potential therapeutic approach for BPAN.

Poland's NBIA Meetings Unite Global Community

December 2023

In October, the international NBIA community witnessed a series of significant moments. These gatherings represented an important stride in advancing research and collaboration within our community.

Researchers, clinicians, and patient advocacy leaders at the BPAN Workshop in Warsaw, Poland, October 17-18.

As the Research Program Director for our organization, I had the privilege of participating in impactful gatherings - a BPAN Workshop, NBIA Poland’s first conference and an NBIA Alliance meeting. Being part of these sessions proved very rewarding as I witnessed the passion and commitment among our dedicated researchers, clinicians, and patient organization leaders.

The BPAN Workshop's goal was to identify and address opportunities for therapeutic development in Beta propeller Protein-Associated Neurodegeneration (BPAN). It was organized by our sister organization, Stichting Ijzersterk, in collaboration with three European BPAN researchers: Rachel Wise of Ludwig Maximillian University in Germany, Mario Mauthe of University Medical Center Groningen in The Netherlands, and Apostolos Papandreou of University College London in the UK.

Funded by the European Joint Program on Rare Diseases (EJP-RD) Networking Support Scheme, this pioneering initiative drew thirty participants from ten countries. Unlike traditional scientific meetings, the event was centered around interactive discussions between all participants to identify the greatest barriers to basic, translational, and clinical research for BPAN and to foster networking and resource sharing among scientists.

Discussions encompassed enrolling BPAN patient data in the TIRCON registry, seeking a BPAN biomarker essential for future clinical trials, strategies to expand the BPAN research network, increasing international collaborations and nurturing young scientists' careers.

Joost Schimmel, a board member of Stichting Ijzersterk, remarked, “Scientists are going to generate a list of available resources to study BPAN, which will accelerate our understanding of the disease, and I think this networking event could be a good starting point for a joint European grant application to study BPAN.”

NBIA Alliance Representatives: Joost Schimmel, Stichting Ijzersterk, Ovidiu Botezán, NBIA Hungary, Fatemeh Mollet, NBIA Suisse, Patricia Wood, NBIA Disorders Association, Maciej Cwyl, NBIA Poland, Amir, NBIA Suisse, Silvia Cappa, AISNAF, Serena Bertoldi, AISNAF. On screen: Top right: Amber Denton, NBIA Disorders Association, Markus Nielbock, Hoffnungsbaum, e.V., Michelle Sheppard-Whalen, NBIA Canada. Not pictured but at research meeting: Antonio Lopez, ENACH.

An official report of the workshop and a BPAN landscape analysis study is being finalized by the consulting firm Science Compass. When available, it will be disseminated to the BPAN community by the patient advocacy organizations that financed the analysis. This study will help drive future BPAN grant initiatives.

The BPAN Workshop concluded on Wednesday at 2 pm, and at 4:30 pm, representatives from CoA Therapeutics met with six NBIA Alliance members in person and others via Zoom to hear the latest update on their upcoming clinical trial set to start in 2024. Afterward, we held an Alliance meeting where each organization presented its ongoing projects, paving the way for discussions on potential research grant collaborations aligned with our common goals. An important objective on our agenda was determining the total count of NBIA families served by Alliance members without duplication while safeguarding our families' privacy. Updates to the NBIA Alliance website are also in the works.

These in-person NBIA research meetings serve as a vital platform for Alliance members to strengthen connections and reaffirm our dedication to a global NBIA community striving toward shared goals.

On Thursday and Friday, "Scientists for the NBIA Community," hosted by NBIA Poland, held its meeting featuring comprehensive scientific presentations on various NBIA disorders. The conference aimed to unite patient families, physicians and researchers to learn about the need for therapies and establish international cooperation among research centers, associations and the NBIA community.

Approximately 150 attendees were present, including families from Poland. Simultaneous translation of 22 research presentations in English or Polish meant everyone in attendance could understand all the information. Some researchers shared not-yet-published work, and the talks led to lively discussions with those in the audience, who asked many questions about the scientific information shared. There was also plenty of time for researchers and clinicians to network, discuss possible future collaborations, and share their work more informally.

After the conclusion of the meeting on Friday evening, researchers and patient organization representatives convened to further discuss topics of interest and come to a consensus on future steps. Everyone endorsed Dr. Yapici Zuhal of Istanbul University in Turkey as the host of the 9th Scientific Symposium for NBIA disorders next year.

Beyond the scientific discourse, NBIA Poland was a gracious and welcoming host, organizing a tour of The Royal Castle in Old Town, Warsaw, on Saturday, followed by a traditional Polish lunch.

It was an important week for so many in the NBIA community who came together worldwide and shared their work, ideas and friendship.

Participants at the "Scientists for the NBIA Community" meeting held in Warsaw, Poland, Oct. 19-20, 2023. NBIA Poland hosted the meeting.

INAD Gene Therapy in the UK Receives EU and US Orphan Drug Designation

December 2023

Bloomsbury Genetic Therapies Limited, based in London, has received orphan drug designations (ODD) from both the European Commission (EC) and the US Food and Drug Administration (FDA) for BGT-INAD, an investigational AAV9 gene therapy to treat Infantile Neuroaxonal Dystrophy (INAD). This therapy offers a potentially curative option for INAD patients through a single cerebrospinal fluid (CSF) injection.

In the US, an ODD designation, which is for diseases with fewer than 200,000 affected US individuals, opens doors for grant opportunities, FDA user-fee benefits, tax advantages, and a seven-year market exclusivity upon regulatory approval. If approved for marketing, the EU provides a similar designation with ten years of market exclusivity.

Bloomsbury also secured a rare pediatric disease designation in the US. They also received a Type B Pre-Investigational New Drug Application (IND) meeting with the FDA, obtaining detailed advice on their plans for BGT-INAD's clinical development.

According to Adrien Lemoine, Co-Founder & CEO of Bloomsbury, the Pre-IND meeting's paramount benefit lies in receiving early insights from the FDA and understanding their expectations for the drug development program. Lemoine expressed satisfaction with the meeting, citing active engagement and constructive guidance from the FDA.

Collaborating with the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) and following June feedback, Bloomsbury is progressing through preclinical studies for BGT-INAD. These studies have already shown compelling preclinical efficacy data in partnership with University College London (UCL) in preparation for a Phase 1/2/3 clinical trial in Europe and the US.

Anticipating completion of efficacy studies early next year, the next steps involve rodent biodistribution/toxicology studies and obtaining a vector adhering to strict regulatory standards and Good Manufacturing Practices before initiating a clinical trial.

Lemoine stated that Bloomsbury anticipates filing an IND to start a clinical trial no earlier than 2025, with the trial slated for 2025/2026, considering the necessary time for these comprehensive activities and contingent upon their funding success.