The Norwegian Academy of Science and Letters today announced the 2022 Kavli Prize Laureates in the fields of astrophysics, nanoscience and neuroscience. Eleven scientists from five countries are honored for their research that has transformed our understanding of the big, the small and the complex. Three of the Laureates in the Neuroscience category are NAM Members.
Before scientists mapped the human genome in the early 2000s, the quest for genes was a laborious process. Four persistent neuroscientists are recognized for pioneering the discovery of genes underlying a range of serious brain disorders and establishing a blueprint for neuroscience research, diagnosis and treatment for Fragile X syndrome, spinocerebeller ataxia, Rett syndrome, and rare forms of epilepsy and autism spectrum disorder.
“These scientists discovered the genetic basis of multiple brain disorders, and elucidated the pathways by which these genes work,” says Chair of the Neuroscience Committee, Kristine B. Walhovd.
Harry T. Orr (elected in 2014) and Huda Y. Zoghbi (elected in 2000) independently discovered ATAXN1, the gene responsible for spinocerebellar ataxia 1 (SCA1), a disease in which neurons in the cerebellum degenerate and cause the loss of balance and coordination; it is progressive, permanent and often fatal. Working together, Orr and Zoghbi discovered that a similar repeat expansion causes SCA1 and discovered that the mutation caused proteins to misfold and clump together in cerebellar neurons, eventually leading to death. Additionally, Orr’s work showed the disease could be treated and his methodology is one of the main models being used for studying neurodegenerative diseases today.
Zoghbi also uncovered the gene MECP2, which causes Rett syndrome, a rare genetic neurological disorder that primarily presents in young girls, often with autism-like symptoms, and results in devastating motor and cognitive symptoms. Zoghbi discovered that changes in the level of MECP2, a repressor of gene expression is essential for the normal function of many types of neurons in the brain. MECP2 is one of the first identified epigenetic causes for a brain disorder. Her research found that MECP2 affects hundreds of neurons and genes and that normalizing MECP2 levels through oligonucleotide therapy reverses the gene’s effects.
Christopher A. Walsh (elected in 2013) discovered more than three dozen neurological disease genes, such as the “double cortex” syndrome, a rare neuronal migration disorder that presents with seizures and intellectual impairment and is seen almost exclusively in females. His research identified genetic mutations that underlie disorders affecting the cerebral cortex and can cause structural malformations that range from subtle to profound, including some forms of epilepsy and autism spectrum disorders. Many of these discoveries came from one of Walsh’s key innovations to study recessive mutations in geographically isolated families. In some of those children, Walsh made an intriguing discovery – mutations that were present in some but not all the cells of the body. They are called somatic mutations and can accumulate slowly during brain development.
Jean-Louis Mandel was also recognized, having discovered an unusual mutation in a gene on the X chromosome that causes fragile X syndrome, an inherited form of intellectual disability, including autism and most commonly presents in males.