Publications by authors named "Kara M Place"
Article Synopsis
- Amyotrophic lateral sclerosis (ALS) is a lethal condition caused by the degeneration of motor neurons, leading to increased cortical hyperexcitability and reduced intracortical inhibition.
- Researchers used a mouse model to show that parvalbumin interneurons are less active before ALS symptoms appear, which contributes to motor neuron hyperexcitability.
- By enhancing the activity of these interneurons in the primary motor cortex through targeted gene therapy, they were able to improve inhibition, slow the progression of ALS symptoms, and extend the life span of the mice, offering new insights into potential treatments for the disease.
Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice.
View Article and Find Full Text PDFSplice-site defects account for about 10% of pathogenic mutations that cause Mendelian diseases. Prevalence is higher in neuromuscular disorders (NMDs), owing to the unusually large size and multi-exonic nature of genes encoding muscle structural proteins. Therapeutic genome editing to correct disease-causing splice-site mutations has been accomplished only through the homology-directed repair pathway, which is extremely inefficient in postmitotic tissues such as skeletal muscle.
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