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Neurofilament Light Chain as a Biomarker of Hereditary Transthyretin-Mediated Amyloidosis.
Ticau, Simina; Sridharan, Gautham V; Tsour, Shira; Cantley, William L; Chan, Amy; Gilbert, Jason A; Erbe, David; Aldinc, Emre; Reilly, Mary M; Adams, David; Polydefkis, Michael; Fitzgerald, Kevin; Vaishnaw, Akshay; Nioi, Paul.
Afiliación
  • Ticau S; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Sridharan GV; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Tsour S; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Cantley WL; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Chan A; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Gilbert JA; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Erbe D; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Aldinc E; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Reilly MM; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Adams D; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Polydefkis M; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Fitzgerald K; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Vaishnaw A; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
  • Nioi P; From Alnylam Pharmaceuticals (S.T., G.V.S., S.T., W.L.C., A.C., J.A.G., D.E., E.A., K.F., A.V., P.N.) , Cambridge, MA; MRC Centre for Neuromuscular Diseases (M.M.R.), UCL Queen Square Institute of Neurology, London, UK; AP-HP (D.A.), Université Paris-Saclay, CHU Bicêtre, INSERM U1195, Le Kremlin Bic
Neurology ; 96(3): e412-e422, 2021 01 19.
Article en En | MEDLINE | ID: mdl-33087494
ABSTRACT

OBJECTIVE:

To identify changes in the proteome associated with onset and progression of hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, we performed an observational, case-controlled study that compared proteomes of patients with ATTRv amyloidosis and healthy controls.

METHODS:

Plasma levels of >1,000 proteins were measured in patients with ATTRv amyloidosis with polyneuropathy who received either placebo or patisiran in a Phase 3 study of patisiran (APOLLO), and in healthy controls. The effect of patisiran on the time profile of each protein was determined by linear mixed model at 0, 9, and 18 months. Neurofilament light chain (NfL) was further assessed with an orthogonal quantitative approach.

RESULTS:

Levels of 66 proteins were significantly changed with patisiran vs placebo, with NfL change most significant (p < 10-20). Analysis of changes in protein levels demonstrated that the proteome of patients treated with patisiran trended toward that of healthy controls at 18 months. Healthy controls' NfL levels were 4-fold lower than in patients with ATTRv amyloidosis with polyneuropathy (16.3 pg/mL vs 69.4 pg/mL, effect -53.1 pg/mL [95% confidence interval -60.5 to -45.9]). NfL levels at 18 months increased with placebo (99.5 pg/mL vs 63.2 pg/mL, effect 36.3 pg/mL [16.5-56.1]) and decreased with patisiran treatment (48.8 pg/mL vs 72.1 pg/mL, effect -23.3 pg/mL [-33.4 to -13.1]) from baseline. At 18 months, improvement in modified Neuropathy Impairment Score +7 score after patisiran treatment significantly correlated with reduced NfL (R = 0.43 [0.29-0.55]).

CONCLUSIONS:

Findings suggest that NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, enable earlier diagnosis of patients with ATTRv amyloidosis, and facilitate monitoring of disease progression. CLASSIFICATION OF EVIDENCE This study provides Class III evidence that NfL levels may enable earlier diagnosis of polyneuropathy in patients with ATTRv amyloidosis and facilitate monitoring of disease progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Neurofilamentos / Proteoma / Neuropatías Amiloides Familiares Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2021 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas de Neurofilamentos / Proteoma / Neuropatías Amiloides Familiares Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Neurology Año: 2021 Tipo del documento: Article