Myrtelle is investigating potential gene therapies for Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum Syndrome.
Myrtelle’s program in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum (H-ABC) uses a nonpathogenic recombinant adeno-associated virus (rAAV) to deliver a functional copy of the human TUBB4A gene directly to the central nervous system (CNS) to target oligodendrocytes, since TUBB4A mutations are the underlying cause of H-ABC. H-ABC is autosomal dominant brain disorder, although most often H-ABC occurs due to a new genetic change occurring for the first time in a person with the condition. TUBB4A mutations disrupt the ability of oligodendrocytes to make myelin.
H-ABC is characterized by extrapyramidal movement abnormalities, spasticity, cerebellar ataxia and sometimes epilepsy, along with hypomyelination and atrophy of the putamen, caudate nucleus, and cerebellum on MRI. Onset ranges from neonatal to childhood, with delayed early development and slow to more rapid neurological deterioration. There are no effective therapies available for PMD, and currently, patients receive only palliative treatments.
H-ABC, a form of leukodystrophy, arises from a genetic mutation impacting the brain’s white matter. This critical area of the brain is enriched with myelin, a vital substance that insulates neurons, facilitating efficient communication between them. At the heart of H-ABC syndrome lies a mutation in the TUBB4A gene. This gene is instrumental in producing microtubules, the cellular structures responsible for transporting essential components within cells. Understanding this genetic foundation is key to comprehending how H-ABC affects brain function and opens pathways for potential treatments and interventions.
The mutation characteristic of H-ABC specifically impairs the brain’s oligodendrocytes, the cells responsible for myelin production. Myelin is crucial for insulating neurons and ensuring rapid signal transmission. Insufficient myelin production, known as hypomyelination, significantly hinders children’s motor and speech development. Typically manifesting in early childhood, H-ABC’s effects are most evident in the challenges children face with walking and speaking. Early recognition of these symptoms is vital for intervention and support, enhancing the quality of life for those affected by this condition.
Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) is a neurological disorder characterized by underdevelopment (hypomyelination) of the brain’s white matter and atrophy (shrinking) of the basal ganglia and cerebellum. These brain areas are crucial for movement control, coordination, and other functions. The condition typically leads to a range of neurological symptoms, including movement disorders, muscle stiffness, and developmental delays.
Diagnosis of H-ABC typically involves a combination of clinical evaluation, imaging studies (like MRI), and genetic testing. Magnetic Resonance Imaging (MRI) can show characteristic patterns of hypomyelination and atrophy in specific brain regions. Genetic testing is used to confirm a diagnosis by identifying mutations in the TUBB4A gene, which is known to cause H-ABC.
Currently, there is no cure for H-ABC, and treatment focuses on managing symptoms and improving quality of life. This may include physical therapy, medications to control muscle stiffness and movement disorders, and other supportive therapies. Regular follow-up with a team of healthcare professionals specializing in neurology, physical therapy, and other relevant fields is essential for optimal care.
H-ABC is usually caused by mutations in the TUBB4A gene and is inherited in an autosomal dominant pattern. This means a mutation in just one copy of the gene can cause the disorder. However, many cases are due to new mutations and occur in people with no family history of the condition. Genetic counseling can provide families with information about the risk of passing the condition to future generations and the implications for family planning.