Identification of small and large molecule pain therapeutics that target the genetically validated voltage-gated sodium channel Na V1.7 is a challenging endeavor under vigorous pursuit. The monoclonal antibody SVmab1 was recently published to bind the Na V1.7 DII voltage sensor domain and block human Na V1.7 sodium currents in heterologous cells. We produced purified SVmab1 protein based on publically available sequence information, and evaluated its activity in a battery of binding and functional assays. Herein, we report that our recombinant SVmAb1 does not bind peptide immunogen or purified Na V1.7 DII voltage sensor domain via ELISA, and does not bind Na V1.7 in live HEK293, U-2 OS, and CHO-K1 cells via FACS. Whole cell manual patch clamp electrophysiology protocols interrogating diverse Na V1.7 gating states in HEK293 cells, revealed that recombinant SVmab1 does not block Na V1.7 currents to an extent greater than observed with an isotype matched control antibody. Collectively, our results show that recombinant SVmab1 monoclonal antibody does not bind Na V1.7 target sequences or specifically inhibit Na V1.7 current.

Pain is a under‐recognized association of leucine‐rich glioma‐inactivated 1 (LGI1) and contactin‐associated protein‐like 2 (CASPR2) antibodies. Of 147 patients with these autoantibodies, pain was experienced by 17 of 33 (52%) with CASPR2‐ versus 20 of 108 (19%) with LGI1 antibodies ( p = 0.0005), and identified as neuropathic in 89% versus 58% of these, respectively. Typically, in both cohorts, normal nerve conduction studies and reduced intraepidermal nerve fiber densities were observed in the sampled patient subsets. In LGI1 antibody patients, pain responded to immunotherapy ( p = 0.008), often rapidly, with greater residual patient‐rated impairment observed in CASPR2 antibody patients ( p = 0.019). Serum CASPR2 antibodies, but not LGI1 antibodies, bound in vitro to unmyelinated human sensory neurons and rodent dorsal root ganglia, suggesting pathophysiological differences that may underlie our clinical observations. ANN NEUROL 2021;90:683–690

for patients diagnosed with psoriasis. The observed prevalence of psoriasis in MS patients was 12.19% however, the true prevalence is likely to be much higher as various symptoms of psoriasis were reported by a much larger proportion of MS patients. Of the 72 cases without psoriasis, various skin symptoms that were reported were intermittent irritation (for at least 6 months) or erythematous rash (35.4%), seasonal skin changes (39.0%) and thickened scaly skin behind ears and scalps (18.3%). Moreover, 18.3% had flaky, peeling or scaly skin while 24.4% experienced dandruff; 17.1% reported nail changes, and 13.4% reported a family history of psoriasis. The study also showed that combined psoriasis and eczema was relatively common at 3.7%. Conclusions In this pilot study there is a high prevalence of psoriasis in patients with MS suggesting an immunopathological association between the two diseases and indicates that further studies should be done to elucidate common mechanisms, and the nature of this phenotype.

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