Approximately 5,000 people in the U.S. develop amyotrophic lateral sclerosis (ALS) each year. On average, they survive for only two to five years after being diagnosed, according to the Centers for Disease Control and Prevention.
University of California - San DiegoNov 8 2024 Approximately 5,000 people in the U.S. develop amyotrophic lateral sclerosis each year. On average, they survive for only two to five years after being diagnosed, according to the Centers for Disease Control and Prevention. The rapidly progressing neurodegenerative disease causes the death of neurons in the brain and spinal cord, resulting in muscle weakness, respiratory failure and dementia.
By the time you see a patient with ALS and you see the TDP-43 protein aggregated in the cytoplasm, it's like the accident site with all the cars crashed already, but that's not the initiating event." Yeo and his team screened for RNA-binding proteins that might influence CHMP7 build-up in the nucleus. This yielded 55 proteins, 23 of which had a potential connection to ALS pathogenesis. Inhibiting the production of several of these proteins led to an increase in CHMP7 in the nucleus.
"You can actually fix the localization of this CHMP7 protein and therefore all of the downstream effects," said Norah Al-Azzam, first author of the study, then a neurosciences student in the Yeo lab who went on to earn her Ph.D. in spring 2024. This hints at the possibility that using risdiplam to raise SMN levels could prevent ALS from developing past the earliest stage of the disease.
Amyotrophic Lateral Sclerosis Brain Cell Cytoplasm Dementia Gene Gene Expression Medicine Motor Neurons Muscle Muscular Atrophy Neurodegenerative Disease Neuron Neurons Ph Protein Research Respiratory RNA Sclerosis Spinal Muscular Atrophy Splicing TDP-43 Therapeutics
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