ArticlePain2017
CRISPR/Cas9 editing of Nf1 gene identifies CRMP2 as a therapeutic target in neurofibromatosis type 1-related pain that is reversed by (S)-Lacosamide.
Article in Pain, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 88 citations in OpenAlex.
- Targeting CRMP2 for Chronic Pain: From Molecular Mechanisms to Therapeutic Strategies.Biomedicines · 2026Review
- Sequential membrane remodeling by cholesterol distinctly modulates HCN channels in naïve and neuropathic DRG neurons.The Journal of general physiology · 2026Article
- Efficient genetic perturbation of murine sensory neurons in vivo using CRISPR/Cas9.The journal of pain · 2026Article
- Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neurofibromin 1 (International journal of molecular sciences · 2026Article
- Review
- Anti-CV2/CRMP5 autoantibodies as drivers of sensory neuron excitability and pain in rats.Nature communications · 2025Article
- Article
- Synergizing CRISPR-Cas9 with Advanced Artificial Intelligence and Machine Learning for Precision Drug Delivery: Technological Nexus and Regulatory Insights.Current gene therapy · 2025Review
- Membrane lipid nanodomains modulate HCN pacemaker channels in nociceptor DRG neurons.Nature communications · 2024Article
- Pain Related Quality of Life in Neurofibromatosis Type 1: A Narrative Review.Current pain and headache reports · 2024Review
- Efficacy, safety, and tolerability of adjunctive Lacosamide therapy for focal seizures in young children aged ≥1 month to ≤4 years: A real-world study.CNS neuroscience & therapeutics · 2024Article
- Schwann cells modulate nociception in neurofibromatosis 1.JCI insight · 2024Article
- Advances in CRISPR-Cas technology and its applications: revolutionising precision medicine.Frontiers in genome editing · 2024Review
- Neurologic orphan diseases: Emerging innovations and role for genetic treatments.World journal of experimental medicine · 2023Review
- Chronic pain recruits hypothalamic dynorphin/kappa opioid receptor signalling to promote wakefulness and vigilance.Brain : a journal of neurology · 2023Article
- Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in chronic constriction injury (CCI) rats.Channels (Austin, Tex.) · 2022Article
- Inherent and Composite Hydrogels as Promising Materials to Limit Antimicrobial Resistance.Gels (Basel, Switzerland) · 2022Review
- Time-Dependent Changes in Protein Composition of Medial Prefrontal Cortex in Rats with Neuropathic Pain.International journal of molecular sciences · 2022Article
- Green Light Antinociceptive and Reversal of Thermal and Mechanical Hypersensitivity Effects Rely on Endogenous Opioid System Stimulation.The journal of pain · 2021Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
Abstract
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. Patients with NF1 commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by patients with NF1. However, behavioral assessments of Nf1 mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain. Targeted intrathecal delivery of guide RNA/Cas9 nuclease plasmid in combination with a cationic polymer was used to generate allele-specific C-terminal truncation of neurofibromin, the protein encoded by the Nf1 gene. Rats with truncation of neurofibromin, showed increases in voltage-gated calcium (specifically N-type or CaV2.2) and voltage-gated sodium (particularly tetrodotoxin-sensitive) currents in dorsal root ganglion neurons. These gains-of-function resulted in increased nociceptor excitability and behavioral hyperalgesia. The cytosolic regulatory protein collapsin response mediator protein 2 (CRMP2) regulates activity of these channels, and also binds to the targeted C-terminus of neurofibromin in a tripartite complex, suggesting a possible mechanism underlying NF1 pain. Prevention of CRMP2 phosphorylation with (S)-lacosamide resulted in normalization of channel current densities, excitability, as well as of hyperalgesia following CRISPR/Cas9 truncation of neurofibromin. These studies reveal the protein partners that drive NF1 pain and suggest that CRMP2 is a key target for therapeutic intervention.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.