n-Lorem Foundation ASO for the Deep Intronic Mutation Causing APBD Receives FDA Approval for n-of-1 Clinical Trials
February 24, 2026
The APBD Research Foundation is excited to share with our community that the n-Lorem Foundation has received FDA approval to proceed with n-of-1 clinical trials for a specialized treatment targeting the APBD deep intronic mutation.
In a September 2025 newsletter article, we shared that researchers at the n-Lorem Foundation had published their work which evaluated the ability for antisense oligonucleotides (ASOs) to treat the deep intronic variant in GBE1 and restore enzyme levels and activity. The ASO targets the GBE1 RNA that is produced from the gene which serves as the blueprint for making the glycogen branching enzyme that is effected in APBD. Originally discovered by Columbia University researcher Dr. H. Orhan Akman, the deep intronic GBE1 variant was found to be the hidden mutation in “manifesting heterozygote” patients -- individuals that had symptoms consistent with APBD but only had one mutation identified.
The n-Lorem Foundation has championed ASO therapies for patients with “nano-rare” genetic mutations affecting less than 30 known individuals worldwide. This means that each eligible patient is enrolled in their own individualized trial (“n-of-1”) with special considerations for personal symptoms and personal disease progression. This is quite different from traditional clinical trials that may recruit dozens or even hundreds of patients.
The FDA authorization to proceed with the study means that the GBE1 ASO n-of-1 trial clinician investigators can move forward with getting institutional review board approval and preparing for their first ASO treatments.
Amy Williford, PhD – n-Lorem Foundation’s Vice President of Foundation Development and External Relations -- shared, “While this news from the FDA is incredibly encouraging, there is still a lot that we need to learn about this ASO treatment. Each patient is unique and will be considered as an individual, not a patient cohort in these n-of-1 clinical trials.”
This announcement is an exciting step forward as we continue to work towards disease-modifying treatments. While treatment is restricted to the deep intronic mutation, the outcomes of these n-of-1 trials will inform future APBD clinical trials and support our understanding of how to measure symptom improvement by identifying treatment-responsive biomarkers.
Who may be eligible for this treatment? Since the ASO is meant to specifically bind to the deep intronic GBE1 variant, only those individuals who carry this mutation could be treated by the ASO therapy. Additionally, as this is not a standard clinical path, any patient that might be amenable to the treatment would need to go through n-Lorem’s process with a committed physician at an academic institution capable of supporting this treatment. Patients who have positive genetic testing for the deep intronic mutation can work with their physician, neurologist, or another specialist to submit an application to the n-Lorem Foundation to be considered for treatment. Today, n-Lorem is only able to treat patients who reside in the United States, but hopes to be able to expand to other countries in the future.
RELATED LINKS:
- Determine if you have the deep intronic mutation
- Treating the Rarest of the Rare: A Conversation with Dr. Amy Williford of n-Lorem Foundation