Congenital White Matter Disease

Dr. Hitoshi Osaka is a Director at the Tochigi Children's Medical Center, a Professor at Jichi Medical University, Chief of the Neurology Department of Pediatrics at the Kanagawa Children's Medical Center, and Investigator of Information and Cellular Function, PRESTO at the Japan Science and Technology Corporation (JST). Dr. Osaka completed his Residency at the Kanagawa Children's Medical Center, Yokohama; his Postdoctoral fellowship from the Department of Pharmacology, School of Medicine, University of California, San Diego, CA; and his Research fellowship from the Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry. Dr. Osaka is a board member of the Japan Pediatric Society, a board member of the Japanese Society of Pediatric Neurology, the President of the Japanese Mitochondrial Society, a council member of the Japanese Epilepsy Society, a council member of the International Cooperative Genetic Disease Gene Therapy Forum, and a council member of the Neurometabolic Diseases Research Group. His main research area is therapy for genetic neurological disorders.

About the session:

Congenital White Matter Disease (Congenital Cerebral Leukodystrophy): 
In 1989, a genetic abnormality in PLP1 was identified as a cause of disease, followed by discoveries of abnormalities in MBP, GJC2, SOX10, MCT8, POLR3, TMEM106B, AIFM1and etc., showing diverse genetic conditions. Congenital cerebral leukodystrophy symptoms include spastic tetraparesis, nystagmus, intellectual disability, cerebellar disorders (ataxia, tremor), basal ganglia disorders (rigid contracture, dystonia), and epilepsy. Infants often present with hypotonia, increasing tendon reflexes, and spastic limb paralysis. MRI aids in diagnosis, and causative genes can be identified in 80-90% of cases. Therapies include microRNA therapy using adeno-associated virus to suppress PLP1 (Li et al. 2019), antisense oligonucleotides (Elitt et al. 2020), and Triac for MCT8 deficiency, showing effectiveness in trials (Groenewege et al. 2019). Understanding genetic diversity in congenital cerebral white matter dysplasia reveals crucial myelination mechanisms, enabling new DNA, RNA, protein, and cell-level therapies.

By attending this session, you will be able to learn the following points:

• To know the myelination processes and distinguish abnormal states: hypomyelination and dysmyelination.
• To understand the genetic abnormalities leading to pathophysiology associated with congenital cerebral leukodystrophy: PLP1, MBP, GJC2, SOX10, MCT8, POLR3, etc.
• To recognize the clinical symptoms of congenital cerebral leukodystrophy: spastic tetraparesis, nystagmus, intellectual disability, cerebellar disorders, basal ganglia disorders, and epilepsy.
• To explore current therapeutic approaches: stem cell therapy, microRNA therapy for PLP1, antisense oligonucleotides, and Triac for MCT8 deficiency.

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