A groundbreaking study by MIT neuroscientists has made a significant breakthrough in treating fragile X syndrome, the most common genetically-caused autism spectrum disorder.
A recent study by MIT neuroscientists at The Picower Institute for Learning and Memory has made a significant breakthrough in treating fragile X syndrome, the most common genetically-caused autism spectrum disorder. ‘The research team discovered that augmenting a specific molecular subunit of ‘NMDA’ receptors can reduce hallmarks of fragile X in mouse models of the disorder.’
Fragile X syndrome is a genetic disorder caused by a mutation on the X chromosome, leading to intellectual disability and physical characteristics.
It affects approximately 1 in 4,000 males and 1 in 8,000 females.
The condition is characterized by delayed speech development, learning disabilities, and distinctive physical features such as a long face and large ears.
Fragile X syndrome is often associated with autism spectrum disorder and attention deficit hyperactivity disorder (ADHD).
Early diagnosis and intervention can significantly improve the quality of life for individuals affected by this condition.
Fragile X syndrome is a genetic disorder caused by an excess of the protein FMRP, which disrupts normal brain function and leads to autism-like symptoms. ‘The Picower Institute’s research team has been studying this condition for over two decades, with previous studies showing that fragile X and another autism disorder, tuberous sclerosis (Tsc), represent two ends of a continuum of protein synthesis in the same neurons.’
Fragile X mental retardation protein (FMRP) is an RNA-binding protein that plays a crucial role in regulating gene expression.
It is encoded by the FMR1 gene and is predominantly expressed in the brain.
FMRP binds to messenger RNA (mRNA) molecules, controlling their translation into proteins.
This process is essential for neuronal development, synaptic plasticity, and learning and memory formation.
Mutations in the FMR1 gene lead to Fragile X syndrome, a genetic disorder causing intellectual disability, behavioral problems, and physical characteristics.
The new study focuses on the NMDA receptor, which plays a crucial role in how neurons synthesize proteins to regulate their connections with other neurons. ‘The researchers discovered that targeting a specific molecular subunit of NMDA receptors, called GluN2B, can reduce excessive bulk protein synthesis and lead to other key improvements.’
NMDA receptors are a subtype of glutamate receptors found in the brain.
They play a crucial role in synaptic plasticity, learning, and memory formation.
These receptors are named after their selective sensitivity to N-methyl-D-aspartate (NMDA).
When activated, they allow positively charged ions to flow into the neuron, inducing a postsynaptic potential.
NMDA receptors are composed of multiple subunits, including NR1, NR2A-D, and NR3A-B.
Their dysregulation has been implicated in various neurological disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia.
The study’s findings indicate that augmenting signaling through the 2B subunit of NMDA receptors can normalize protein synthesis, alter synaptic plasticity, and increase electrical excitability in fragile X model mice. ‘The researchers also tested an experimental drug called Glyx-13, which binds to the 2B subunit to augment signaling.’ They found that this treatment can also normalize protein synthesis and reduce sound-induced seizures in fragile X mice.
The study’s findings have significant implications for the development of new treatments for fragile X syndrome. ‘The researchers hypothesize that targeting the 2B subunit of NMDA receptors may shift the balance of protein synthesis away from an all-too-efficient translation of short messenger RNAs, which leads to excessive bulk protein synthesis.’
While the study’s findings are promising, further research is needed to determine the prospects for Glyx-13 as a clinical drug. However, there are already some drugs in clinical development that specifically target the 2B subunit of NMDA receptors. The Picower Institute’s research team is committed to continuing their work on developing new treatments for fragile X syndrome and other autism-related disorders.
The discovery of a new molecular strategy for treating fragile X syndrome represents a significant breakthrough in our understanding of this complex condition. ‘By targeting the 2B subunit of NMDA receptors, researchers may be able to develop more effective treatments that can improve the lives of individuals with fragile X syndrome and other autism-related disorders.’
