NBIA NEWS & INFORMATION

Update: OHSU CoA-Z in PKAN trial concludes and analysis begins

By Allison Gregory

 December 2022

Allison Gregory, a genetic counselor from the NBIA research group at OHSU, helped manage the CoA-Z trial.

Our NBIA research team at Oregon Health & Science University has concluded the first part of its study of a compound to treat PKAN, called CoA-Z, and will begin analyzing the data to determine its safety, how well it was tolerated, and whether it holds potential as a therapy for PKAN.

Although supply-chain issues brought on by the COVID-19 pandemic caused us to limit the trial’s duration, its home-based, remote design allowed the study to continue without needing to be changed significantly to adapt to COVID restrictions.

The first subjects were enrolled in December of 2019, and enrollment continued through September of 2021. During that time, 77 children and adults with PKAN joined. The study had a high retention rate, meaning most participants were able to continue until their two-year study time had ended, or until the active part of the study ended in summer 2022.

While completing everyone’s participation was a huge milestone, there is still much work to be done. Hundreds of biomarker blood samples collected and frozen over nearly three years are being processed and analyzed in the lab.

Next steps are to check all of the data and collaborate with OHSU statisticians to analyze the information, including data on complications and compliance with the study, and clinical information from the PKANready natural history study that ran in parallel with the trial.

Meanwhile, teams in The Netherlands and the U.K. are moving forward with similar trials. The Dutch team is well along with its trial, and the U.K. team expects to launch in 2023. The trials differ in valuable ways that we hope will provide more information to advance CoA-Z development.

To everyone who participated and has supported the trial, we send our thanks.

Care guidelines for PLAN now under development
By Patricia Wood

 December 2022

Consensus guidelines for treating and managing a form of NBIA known as PLAN, or PLA2G6-associated neurodegeneration, are now underway, thanks to support from four organizations funding the project.

This is the third NBIA disorder for which researchers have created best practices. The other two are more common forms of NBIA, PKAN and BPAN.

PLAN is a broad spectrum of symptoms, and based on an individual’s age of onset and symptoms, they may be classified as having one of three subtypes: INAD, aNAD or PLA2G6-related dystonia-parkinsonism.

Four organizations collaborated to support “Best practices in the care and management of people with PLAN.” Along with NBIA Disorders Association, the others are INADcure Foundation, a U.S. based nonprofit dedicated to helping those with INAD and other subtypes of PLAN, and sister NBIA organizations AISNAF in Italy and Hoffnungsbaum e.V., in Germany.

Dr. Susan Hayflick, with the NBIA research group at OHSU, is the principal investigator of the PLAN consensus guidelines underway.

Dr. Susan Hayflick of OHSU is the principal investigator, working with colleagues Dr. Jennifer Wilson as lead writer and Allison Gregory, MS, as project leader. This group also developed the best practice guidelines for PKAN and BPAN.

The main objective of this project is to counsel clinicians on the best possible and most acceptable way to address diagnosis, management or treatment of PLAN and its three subtypes. Given that INAD is the most common form of PLAN, a greater portion of the guideline will likely focus on this subtype.

Best practice in the following areas will be addressed: diagnostic evaluation, initial management, pharmacologic and surgical management, monitoring for disease complications, emergency management, educational management, nutrition, psychosocial support and any additional areas identified by participants.

Other leading experts in PLAN will also be asked to contribute, along with select parents, caregivers and the funding patient advocacy organizations. Members of the larger patient and family community and other patient advocacy organizations will be invited to review and comment on a final draft of the guideline during a two-week period.

The project will require about 12 months to submit a draft publication. The total cost is $50,308, comprised of personnel costs that cover the time and efforts of the project team with their professional expertise, project leadership and coordination. Other costs are publication fees for free public access to the paper and travel costs to present findings at two meetings within a year of publication.

8th Scientific Symposium on NBIA held in-person in Switzerland
By Patricia Wood

December 2022 

Meeting in person for the first time since 2017, the 8th International Symposium on NBIA was held in October in scenic Lausanne, Switzerland, on Lake Geneva, attracting 74 participants from 14 countries.

The NBIA Disorders Association has been attending these gatherings of clinicians and scientists since the first one in 2000 — when just 30 people attended — to nurture collaborations and idea exchanges that could lead to new understandings of NBIA and treatments for the disorders.

In addition, our organization since 2014 has been helping by offering travel stipends to early-career scientists who wish to attend the scientific symposium but couldn’t otherwise afford it. This year, we awarded eight stipends totaling $5,000 to those researchers, all of whom presented research or disease-specific information in poster displays at the symposium.

Early-career researchers who received travel grant awards. L-R: Drs. Rachel Wise, Özgür Öztop Çakmak, Fatima Efendic, Robert Spaull, Audrey Soo, Apostolos Papandreou, Kenta Shiina, Iankova Vassilena.

Several early-career scientists sent me emails afterward saying how valuable the experience was and that it has motivated them to continue working on NBIA. It also gave them ideas for research and helped them forge collaborations with fellow attendees.

I was encouraged to see our next generation of NBIA researchers participating in the symposium, with several of them already doing important work on projects led by principal investigators who our organization has funded.

The symposium was lively with many questions and ideas from the audience. Several new collaborations were created during sessions, with researchers sharing how they wanted to work together on a specific idea being discussed.

The program committee was led by Dr. Thomas Klopstock of the Ludwig-Maximilians University Munich in Germany and included Drs. Susan Hayflick of the Oregon Health & Science University in Portland, Valeria Tiranti of Foundation Neurological Institute C. Besta in Milan and Agnès Rötig of Institute Imagine in Paris. Lay advocacy partner Markus Nielbock of Hoffnungsbaum e. V. from Germany and I were also committee members. A local organizing committee led by Fatemeh Mollet of NBIA Suisse handled registration and made sure the symposium ran smoothly.

In addition to the symposium, the NBIA Alliance, which consists of our organization and nine sister groups in other countries, met with CoA Therapeutics to get on an update on its work. Afterward, the alliance met to discuss more ways to work together and plans to overhaul the alliance’s website. Four organizations had members attending the symposium in person and the rest joined the meeting via Zoom.

NBIA Alliance Representatives at symposium L-R: Roberta Scalise, AISNAF; Fatemah Mollet, NBIA Suisse; Joost Schimmel, Stichting Ijzersterk; Patricia Wood, NBIA Disorders Association.

Many thanks to biotech sponsors Chiesi, CoA Therapeutics and Travere Therapeutics, along with NBIA Suisse and Hoffnungsbaum e.V. in Germany who helped make the symposium possible.

Plans were made to hold the 9th symposium in 2024, with the location to be determined later.

Group photo of participants at the 8th International Symposium on NBIA in Lausanne, Switzerland.