Cutaneous biomarkers of therapeutic efficacy in early treatment of hereditary ATTR amyloid polyneuropathy with tafamidis

• DOI: 10.1111/jns.12624
• Publication Date: 2024-05-06T05:48:35Z
• Authors: Karla Cárdenas‐Soto; Xel‐Ha Dominguez; Giovanni Cortes; Felix Tsai; Maria del Mar San...; Paola Guraieb‐Chahin; Benjamín Torres‐O...; Christopher Gibbons; Jeffery W. Kelly; Roy Freeman; Alejandra Gonzále...
• Keywords: Nerve fiber; Amyloid (mycology)

Abstract Background ATTR (ATTRv) amyloidosis neuropathy is characterized by progressive sensorimotor and autonomic nerve degeneration secondary to amyloid deposition caused a misfolded transthyretin protein (TTR). Small fiber an early clinical manifestation of this disease resulting from the dysfunction Aδ C small fibers. Tafamidis, selective TTR stabilizer, has proven its efficacy in earlier stages hATTR. Objectives To evaluate course utility cutaneous pathological biomarkers patients with treated tafamidis compared control patients. Methods Forty diagnosed ATTRv (polyneuropathy disability [PND] scores 0‐II) underwent large neurological evaluations, annual skin biopsies for intraepidermal density (IENFD) index (ADI) estimation. Thirty were allocated receive tafamidis, 10 served as controls. Tafamidis pharmacokinetics analysis was performed who received treatment. Results At baseline, 12% stage PND 0 28% I displayed denervation distal thigh, whereas 23% 38%, respectively, leg. Similarly, 72% 84% had thigh 56% 69% Following 1 year treatment, group showed significant improvement group, revealed following mean differences (1) −9.3 versus −4 points ( p = <.00) patient's total symptom score 6 (NTSS‐6) questionnaire, (2) −2.5 +2.8 Utah Early Neuropathy Score (UENS), (3) +1.2°C −0.6 .01) cold detection thresholds. Among 65% stable or increased IENFD their 27% In contrast, all denervation. The ADI either decreased remained constant 31% 24% leg tafamidis‐treated patients, it rose across group. 4‐year follow‐up, continued display less (mean difference [MD] −3.0 vs. fibers/mm) −4.9 −8.6 fibers/mm). also lower (10 30 amyloid/mm 2 ) (23 40 Plasma concentrations higher reduced deposition. Patients without at baseline delayed progression 4 years. Conclusions Cutaneous assessments are valuable diagnosis measuring neuropathy. treatment slows disease, denervation, skin. Higher plasma associated better outcomes, suggesting that increasing drug dose could achieve response rates. This study describes longest therapeutic trial first report symptoms, function, structural outcomes.