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Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases.
Cambieri, Chiara; Marenco, Marco; Colasanti, Tania; Mancone, Carmine; Corsi, Alessandro; Riminucci, Mara; Libonati, Laura; Moret, Federica; Chimenti, Cristina; Lambiase, Alessandro; Conti, Fabrizio; Garibaldi, Matteo; Inghilleri, Maurizio; Ceccanti, Marco.
Afiliação
  • Cambieri C; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
  • Marenco M; Department of Sense Organs, Sapienza University of Rome, Rome, Italy.
  • Colasanti T; Department of Clinical Internal, Rheumatology Unit, Anesthetic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
  • Mancone C; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Corsi A; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Riminucci M; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Libonati L; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
  • Moret F; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
  • Chimenti C; Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
  • Lambiase A; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy.
  • Conti F; Department of Sense Organs, Sapienza University of Rome, Rome, Italy.
  • Garibaldi M; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • Inghilleri M; Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Sant'Andrea Hospital, Sapienza University, Rome, Italy.
  • Ceccanti M; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
Curr Neuropharmacol ; 21(12): 2543-2549, 2023.
Article em En | MEDLINE | ID: mdl-37357518
BACKGROUND: Variant transthyretin-mediated amyloidosis (ATTR-v) is a well-characterized disease affecting the neurologic and cardiovascular systems. Patisiran has been approved for neurologic involvement as it reduces hepatic synthesis of transthyretin (TTR). Eye involvement is a lateonset feature increasing the risk of glaucoma and cataracts in patients. AIMS: The aim of this case series was to assess whether patisiran can effectively reduce TTR synthesis in such a barrier-protected organ as the eye. METHODS: Two patisiran-treated ATTR-v patients underwent serum and aqueous humor sampling to measure TTR levels detected by SDS-PAGE and immunoblotting. Serum samples were compared to healthy control (HC), whereas aqueous humor samples were compared to non-amyloidotic subjects affected by cataracts and glaucoma. RESULTS: Serum TTR levels representative of hepatic synthesis were sharply lower in treated patients if compared to the HC (-87.5% and -93.75%, respectively). Aqueous humor TTR levels showed mild-tono reduction in treated patients compared to non-amyloidotic subjects with cataracts (-34.9% and +8.1%, respectively) and glaucoma (-41.1% and -2.1%). CONCLUSION: Patisiran does not seem to be as effective in inhibiting ocular TTR synthesis as it is in inhibiting hepatic synthesis. Re-engineering the envelope could allow the drug to target RPE cells thus avoiding any ocular involvement.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article