By Raffaele Pereno – PhD, MBA
AMSTERDAM, the Netherlands – SynaptixBio, a UK-based biopharmaceutical company pioneering antisense oligonucleotide (ASO) therapies for ultra-rare neurological diseases, presented its groundbreaking work on TUBB4A-related leukodystrophy (also known as H-ABC) at the World Orphan Drug Congress (WODC) in Amsterdam.
CheckOrphan spoke with SynaptixBio’s CEO, Dan Williams, at the event. He highlighted, “Our lead compound, SB-19642, is an antisense oligonucleotide designed to silence the toxic TUBB4A mutation responsible for hypomyelination in the brain. By targeting the root genetic cause, our goal is to stop disease progression and ultimately restore neural function in affected children.”
Understanding TUBB4A-Related Leukodystrophy
Leukodystrophies represent a group of more than 50 inherited disorders that damage the brain’s white matter, the myelin sheath insulating nerve fibers. Approximately 9 % of all leukodystrophies are caused by mutations in TUBB4A, which encodes β-tubulin 4A, a structural protein critical for the formation of the neuronal cytoskeleton and proper myelination (Vanderver et al., Ann Neurol 2016).
Mutations in TUBB4A produce abnormal tubulin that disrupts oligodendrocyte cells responsible for forming myelin. The result is hypomyelination, leading to severe motor dysfunction, developmental delay, and progressive neurological decline.
The disease is ultra-rare, affecting an estimated 1 to 3 individuals per million (Orphanet, NORD). To date, roughly 200 patients have been documented worldwide.
The Human Drive Behind the Science
Chief Scientific Officer Dr Michelle Teng, who co-founded SynaptixBio after her daughter’s diagnosis with H-ABC, also established the H-ABC Foundation, a charity that represents patients and their families in the UK. It has compiled a database of UK patients and is looking to grow this internationally.
“This foundation has given families a voice and has accelerated research by connecting clinicians, scientists, and biotech innovators,” said Dr Teng.
From Discovery to Translation
SynaptixBio was founded in 2021 to translate the pioneering research of Dr Adeline Vanderver at the Children’s Hospital of Philadelphia (CHOP) into a treatment for children suffering from this devastating disease.
The company is now working with Evotec SE to finalize pre-clinical validation and GMP manufacturing of SB-19642 to enable a Phase 1/2a first-in-human study.
Clinical Progress and a De-Risked Path Forward
In July 2025, the non-profit n-Lorem Foundation treated the first patient with a TUBB4A ASO under an FDA n-of-1 compassionate-use authorization.
This pioneering case demonstrated human feasibility, regulatory acceptance, and family advocacy for an ASO approach in TUBB4A.
The company plans to initiate GLP toxicology studies in 2026, followed by starting clinical trials in 2027. The goal is to deliver the first disease-modifying therapy for children with TUBB4A leukodystrophy, a condition currently lacking any approved treatment.
Vision and Next Steps
“SynaptixBio’s mission is to transform the lives of children with fatal white-matter disorders through innovative RNA-targeted medicines,” said Dr Teng. “Our approach could redefine how we treat ultra-rare neurological diseases—turning single-patient proof-of-concepts into scalable, regulated therapies.”
For more information, visit www.synaptixbio.com.