Why Direct Cell Targeted Delivery Is the Next Frontier in CNS Gene Therapy

For decades, central nervous system (CNS) gene therapy has approached the brain as a single, undifferentiated target. Myrtelle was built on a different premise: the cell type matters as much as the delivery route.

Myrtelle’s lead program, MYR-101 (rAAV Olig001 ASPA), was designed to directly reach oligodendrocytes, the specialized cells responsible for producing and maintaining myelin, using intracerebroventricular (ICV) administration. As described in the September 2025 Nature Medicine publication, this targeted approach has done precisely what it was engineered to do: reduced NAA accumulation, liberated acetate for myelin synthesis and as a consequence restored myelin in patients with Canavan disease, a rare pediatric neurological disorder caused by ASPA gene mutations.

While Canavan disease is Myrtelle’s lead indication, we intend to apply our unique oligodendrocyte-targeted ICV delivery approach to a broad range of white matter diseases.

The ICV Oligodendrocyte Advantage

Traditional CNS gene therapy, which relies on broad, non-specific delivery, has long struggled with the basic challenge of delivering optimal amounts of the right payload to the right cell type.

Myrtelle’s approach starts by administering MYR-101 directly to the brain via the ICV route. This achieves higher drug concentrations in the target organ, the brain, and reduces systemic side effects typically seen with other routes of administration. We then capitalize on this by using a novel gene delivery rAAV capsid (Olig001) designed to selectively target oligodendrocytes. This is important because myelin, which is essential for healthy functioning of the CNS, is only synthesized in oligodendrocytes. Thus, with these 2 approaches (ICV administration and the oligodendrocyte-targeting capsid delivery system) we aim to efficiently and effectively correct the underlying cause of the disease, including demyelination, rather than simply managing downstream symptoms. This is supported by Phase 1/2 clinical data described in the September 2025 Nature Medicine publication, which demonstrated a favorable safety profile with no treatment related serious adverse events, alongside confirmed biomarker restoration.

To our knowledge, Myrtelle is the only gene therapy company with a direct oligodendrocyte-targeted therapy delivered via ICV administration in clinical development.

This is important because oligodendrocytes are far more than a niche target relevant to one disease. Published research points to oligodendrocyte and myelin biology as a central mechanism in multiple neurological conditions, including:

  • Alzheimer’s Disease: Linked to APOE4 associated pathology
  • Epilepsy: Driving maladaptive myelination and disease progression
  • Huntington’s Disease: Characterized by oligodendrocyte maturation deficits
  • Cognitive Function: Essential for signal coordination, trophic support, metabolic maintenance, and memory formation

Research Spotlight: Broadening the Myelin Landscape

While Canavan disease remains our lead clinical indication, , the approach of using ICV delivery of an oligodendrocyte-targeting gene therapy to optimize efficiency and effectiveness extends directly to other disorders defined by disrupted myelin production or white matter dysfunction.

Myrtelle’s platform expansion strategy includes active program development for:

  • Pelizaeus Merzbacher Disease (PMD)
  • Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H ABC)
  • Multiple System Atrophy (MSA)

Multiple conditions; one scientific foundation. 

Looking Ahead

The regulatory environment for rare disease gene therapy has shifted meaningfully with the support of clinical and patient advocacy engagement. In mid 2026, regulatory precedents established by biotechnology companies like uniQure and REGENXBIO demonstrated the FDA’s willingness to accept existing Phase 1/2 data to support accelerated approval filings…

Myrtelle’s selection for the FDA’s START Pilot Program and our RMAT designation for MYR-101 for Canavan disease place us squarely inside these regulatory opportunities.  Commercial stage manufacturing of MYR-101 for Canavan disease is underway so that when regulatory approval is obtained, Myrtelle is positioned to deliver for Canavan disease first and unlock the broader platform that follows.