Advancing PKAN gene therapy: a collaborative initiative

Research into a gene therapy for pantothenate kinase-associated neurodegeneration (PKAN) is progressing thanks to the commitment of experienced researchers and newly established partnerships.

In 2019, a significant step was taken in PKAN research when the NBIA Disorders Association, in collaboration with NBIA sister organizations AISNAF (Italy) and Hoffnungsbaum e.V. (Germany), awarded seed funding to Dr. Lauriel Earley at the University of North Carolina - Chapel Hill to initiate gene therapy research. However, scientific endeavors are often subject to unexpected changes.

Earley's decision to discontinue her work on PKAN necessitated a seamless transition to Dr. Susan Hayflick at Oregon Health & Science University (OHSU). Hayflick agreed to take over as director in 2019. She brings a wealth of experience and a strong commitment to advancing PKAN research. Dr. Suh Young Jeong, Hayflick's scientific team leader since 2014, was able to bring the project to a close with promising results.

The change of project manager has breathed further life into PKAN gene therapy.

Hayflick was recently contacted by the Loving Loic Foundation, a charitable foundation set up by Sherine and Mark Blackford in honor of their son Loic, who has PKAN. The Blackfords were personally interested in the further development of gene therapy and offered their support.

The Loving Loic Foundation facilitated the contact with Dr. Miguel Sena-Esteves and Dr. Heather Gray-Edwards at the Horae Gene Therapy Center at UMass Chan Medical School (UMass). Sena-Esteves, an expert in the development of adeno-associated virus (AAV)-based gene therapies, and Gray-Edwards, an expert in the use of animal models to better understand disease progression, agreed to work with Hayflick's team. In addition, Dr. Penelope Hogarth from OHSU has joined the team, bringing years of experience with PKAN and expertise in clinical trial design. The clinical trial team also includes Allison Gregory, genetic counselor, Dr. Jenny Wilson, pediatric neurologist, and Alison Freed, clinical research coordinator.

Recent progress reports indicate that the team is redesigning the gene therapy drug to optimize its therapeutic effect. Using the PKAN mouse colony that the OHSU team has developed over the past two decades, it will test several redesigned products to determine which one works best. This laborious process is expected to take at least two years, depending on what the U.S. Food and Drug Administration (FDA) says.

While these critical experiments are underway, hard work is also being done on the design and preparation of the clinical trial. Regular meetings with the FDA are essential at every stage of the process. Feedback and suggestions from the FDA may impact the timeline for progress. At this time, the team does not know when the clinical trial for PKAN gene therapy will begin, but they feel a sense of urgency, as do people in the PKAN family community.

While the researchers in the lab are making great progress, the Loving Loic Foundation continues to play a critical role in supporting this collaborative endeavor by providing crucial financial support and advocacy. It recently received a $21,000 grant, bringing the total amount raised to $182,036 (including in-kind donations) toward the project goal of $5 million. If you would like to learn more, fundraise or contribute to this project, visit lovingloic.org or contact Sherine Blackford at info@lovingloic.org.

Translation of an article from the March 2024 newsletter of the NBIA Disorders Association
https://nbiadisorders.org/news-events/nbia-newsletters/