Myrtelle is investigating potential gene therapies for PMD.
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.
Pelizaeus-Merzbacher Disease (PMD) falls under the category of leukodystrophies, disorders resulting from gene mutations that impact the brain’s white matter. White matter, rich in myelin, facilitates efficient neuron communication. PMD primarily arises from a duplication of the PLP1 gene, leading to an overproduction of proteolipid protein-1 (PLP1) by oligodendrocytes, the cells responsible for myelin synthesis. This excess disrupts normal myelin formation, hindering proper signal transmission in the brain (known as hypomyelination).
PMD symptoms typically emerge early in a child’s life, noticeably affecting their motor skills and cognitive development. Children with PMD often experience shaky movements, coordination difficulties, and challenges in walking. Additionally, they may face obstacles in learning and cognitive functions. Early detection and intervention play a crucial role in managing these symptoms and supporting the child’s development.
Pelizaeus-Merzbacher Disease (PMD) is a genetic disorder that affects the central nervous system. It is characterized by the disruption of myelin, the protective covering that surrounds nerve fibers in the brain and spinal cord. This disruption impairs the ability of nerves to transmit signals efficiently, leading to a range of neurological symptoms. These can include delayed development, motor difficulties, muscle stiffness, and involuntary eye movements.
The diagnosis of PMD typically involves a combination of clinical evaluation, family history, and genetic testing. Magnetic Resonance Imaging (MRI) can also be used to observe the characteristic patterns of myelin disruption in the brain. Genetic testing is crucial as PMD is caused by mutations in the PLP1 gene, which is responsible for the production of a key protein in myelin formation. Early diagnosis can be beneficial for management and intervention strategies.
Currently, there is no cure for PMD, and treatment focuses on managing symptoms and providing supportive care. This may include physical therapy, occupational therapy, and medications to manage specific symptoms like muscle stiffness or movement disorders. Assistive devices and technologies can also be used to improve quality of life and independence. Regular monitoring and supportive care from a team of healthcare professionals are essential for managing the condition effectively.
The prognosis and life expectancy for individuals with PMD vary depending on the severity and type of the disease. Some forms of PMD progress slowly and allow for longer life expectancy, while others may be more severe and progress more rapidly. Quality of life and longevity can be improved with appropriate medical and supportive care. It’s important for families and caregivers to work closely with healthcare providers to address the evolving needs of individuals with PMD throughout their lives.