Myrtelle is advancing a robust pipeline of gene therapy programs using proprietary technologies, vectors, constructs and capabilities. A core area of focus is targeting oligodendrocytes to address underlying causes of disorders involving myelin.
1 Myrtelle’s Phase 1/2 clinical trial of a proprietary gene therapy for Canavan disease (CD) utilizes a proprietary recombinant adeno-associated virus (rAAV) vector that for the first time directly targets oligodendrocytes in the brain. Oligodendrocytes are the cells in the brain responsible for producing myelin, the insulating material that enables proper function of neurons. The production of myelin is affected in CD due to a mutation in the Aspartoacylase gene (ASPA). As a result, patients are affected at birth but may appear normal until several months, when symptoms begin to develop. Poor head control, abnormally large head size, eye tracking difficulty, excessive irritability, severely diminished muscle tone, and delays in reaching motor milestones such as rolling, sitting, and walking are typical. As the disease progresses, seizures, spasticity, difficulties in swallowing, and overall muscle deterioration emerge, with most affected children developing life-threatening complications by ten years of age. The oligodendrocyte-targeted gene therapy is intended to restore ASPA function, thus enabling metabolism of the chemical N-Acetylaspartic Acid (NAA), a chemical abundant in the brain, and supporting myelination. Currently, there is no cure for CD and only palliative treatments are available.
2 Myrtelle’s program in Pelizaeus Merzbacher Disease (PMD) uses a nonpathogenic recombinant adeno-associated virus (rAAV) to deliver gene silencing microRNA (miRNA) directly to the central nervous system (CNS) to target oligodendrocytes. The miRNA is intended to reduce toxic levels of proteolipid protein 1 (Plp1), the underlying cause of PMD. PMD is an X-linked recessive brain disorder of oligodendrocytes that disrupts myelin production. The disease often presents in the first year of life with symptoms that include hypotonia, nystagmus, stridor, and delayed developmental milestones, especially in motor function. PMD is characterized by progressively deteriorating coordination, motor abilities, and intellectual function, leading to early death, often during childhood. There are no effective therapies available for PMD, and currently, patients receive only palliative treatments.
3 Myrtelle’s program to develop a novel gene therapy for DFNB8 genetic hearing loss includes low-dose recombinant adeno-associated virus (rAAV) gene therapy delivery of a therapeutic TMPRSS3 (transmembrane protease, serine 3) gene by local administration directly to the inner ear. Across its gene therapy programs, Myrtelle utilizes direct administration of low-dose gene therapy to target key cell types involved in the disorder, thereby avoiding immune-related and off-target effects that can arise with high-dose gene therapy administration delivered systemically. This strategy, currently being developed for Myrtelle’s central nervous system (CNS) programs, can be leveraged to other therapeutic areas outside the CNS, including adjacent and related areas such as the ear where local gene therapy delivery is potentially advantageous for hearing loss disorders such as DFNB8. Preclinical studies in the mouse model of DFNB8-mediated deafness have demonstrated that delivery of a wild type TMPRSS3 gene was able to promote hair cell and neuron survival and improve hearing function.