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Related Concept Videos

Lateralization01:28

Lateralization

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Brain lateralization refers to the division of mental processes and functions between the two hemispheres of the brain, a phenomenon that optimizes neural efficiency and underpins complex abilities in humans. This specialization allows each hemisphere to perform tasks where it has a comparative advantage, facilitating more refined cognitive capabilities across different domains.
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Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
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Cranial Bones: Lateral View01:27

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The lateral view of the cranium is dominated by temporal, sphenoid, and ethmoid bones.
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Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
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Related Experiment Video

Updated: Feb 10, 2026

Evaluation of Motor Impairment in C. elegans Models of Amyotrophic Lateral Sclerosis
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Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis.

Timothy M Miller1, Merit E Cudkowicz2, Pamela J Shaw3,4

  • 1Department of Neurology, Neuromuscular Medicine, Washington University School of Medicine in St Louis, St Louis, Missouri.

JAMA Neurology
|February 9, 2026
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Summary

Tofersen treatment for SOD1-ALS shows long-term benefits, including improved function and survival. Early initiation of tofersen (an antisense oligonucleotide) is associated with better outcomes in patients with SOD1-ALS.

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Area of Science:

  • Neurology
  • Genetics
  • Pharmacology

Background:

  • Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
  • Approximately 2% of ALS cases are linked to mutations in the superoxide dismutase 1 (SOD1) gene.
  • Tofersen is an antisense oligonucleotide therapy targeting SOD1 protein synthesis.

Purpose of the Study:

  • To evaluate the long-term efficacy and safety of tofersen in adults with SOD1-ALS.
  • To compare outcomes between early and delayed initiation of tofersen treatment.
  • To assess the impact of tofersen on clinical function, neurodegeneration, and survival.

Main Methods:

  • Phase 3 randomized, double-blind, placebo-controlled VALOR trial and its open-label extension (OLE).
  • 108 adults with SOD1-ALS were randomized to tofersen or placebo.
  • Integrated analysis compared early vs. delayed tofersen initiation over extended follow-up periods.

Main Results:

  • Earlier tofersen initiation was associated with numerically less decline in clinical function, respiratory function, muscle strength, and quality of life.
  • Tofersen treatment prolonged survival compared to the expected natural history of SOD1-ALS.
  • Adverse events were generally consistent with ALS progression; serious neurological events were reversible.

Conclusions:

  • Final data demonstrate the clinical benefit of tofersen in SOD1-ALS.
  • Tofersen provides a clear rationale for its use in patients with SOD1 gene variants.
  • Long-term treatment with tofersen shows sustained efficacy and an acceptable safety profile.