Canavan disease is a fatal, inherited leukodystrophy that primarily affects infants and young children, and leads to severe and progressive damage to the brain’s white matter. Life expectancy is typically limited to early childhood or adolescence, and there is no approved treatment or cure.
But there is hope. Since Canavan disease is monogenic – caused by mutations in the ASPA gene – it’s an attractive target for gene therapy. Myrtelle has recently presented and published encouraging interim results from a phase I/II trial of a new, investigational gene therapy, rAAV-Olig001-ASPA.
“The technology for gene delivery is a novel AAV capsid, Olig001, which was developed by a team from the University of North Carolina,” says Olga Flamini, co-Chief Medical Officer of Myrtelle. “The capsid was combined with a healthy copy of the ASPA gene and tested in preclinical studies by Professor Paola Leone. Myrtelle took up the torch and continues the study in clinical trials.”
In Canavan disease, mutations in the ASPA gene lead to a deficiency of the enzyme aspartoacylase. Without this enzyme, N-acetylaspartate accumulates in the brain, disrupting the normal formation and maintenance of myelin – the protective sheath around nerve fibers.
Richard Layer, SVP Head of Pharmacology and Translational Science, explains, “AAV-Olig001 has a preferential tropism for oligodendrocytes in the central nervous system. Identification of the Olig001 capsid was serendipitous for Canavan disease treatment because oligodendrocytes are the key cells in Canavan disease pathology – these cells produce myelin and catabolize N-Acetylaspartate.”
Myrtelle’s interim data, covering eight pediatric participants, showed that the gene therapy was well tolerated, with no serious adverse events. Participants showed decreases in cerebrospinal fluid N-acetylaspartate levels and increases in brain myelin volume, as measured by Synthetic MRI (SyMRI). Functional assessments showed developmental improvements in all participants, with most demonstrating gains across multiple domains based on Mullen Scales of Early Learning compared with historical controls.
“The decrease in N-acetylaspartate levels in cerebrospinal fluid indicate successful expression and function of aspartoacylase and is the first necessary step toward successful therapy for Canavan disease. We also saw improvement in myelin volume after treatment, which is uncharacteristic for the natural course of the disease and indicates reversal of the pathology and brain recovery,” says Olga Famini, Co-Chief Medical Officer.
Further readouts are expected in Q2 2026.
The gene therapy has received several regulatory designations, including Regenerative Medicine Advanced Therapy, Orphan Drug, Rare Pediatric Disease, and Fast Track status from the FDA. Similar designations have been granted by the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency. Myrtelle has signed a worldwide licensing agreement with Pfizer for the therapy.
Jordana Holovach, Head of Communications & Community adds, “I would like to recognize the Canavan families for their unrelenting devotion to the care of their children, support of one another and for allowing us the privilege to ensure their voices are paramount in all that we do. We stand with the community in our mutual desire to finally see an approved treatment for diagnosed children, which we hope will lead to the standardization of newborn screening for Canavan disease, thereby allowing for earlier diagnoses and treatment intervention.”
Myrtelle focuses on treating rare diseases, with a core focus on white matter pathologies. Canavan disease is a special focus and is the company’s most advanced therapeutic program. Myrtelle also has a pipeline addressing other rare diseases, including Pelizaeus-Merzbacher disease, H-ABC, and Multiple System Atrophy, as well as a hearing loss program for DFNB-8 deficiency.
The results, published in Nature Medicine, are one of the first detailed peer-reviewed accounts of in vivo gene therapy targeting oligodendrocytes in a leukodystrophy.
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