Does Patisiran Reduce Ocular Transthyretin Synthesis? A Pilot Study of Two Cases.

Autor:	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.; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy., Lambiase A; Department of Sense Organs, Sapienza University of Rome, Rome, Italy., Conti F; Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy., Garibaldi M; Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Sant'Andrea Hospital, Sapienza University, Rome, Italy., Inghilleri M; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy., Ceccanti M; Department of Human Neuroscience, Centre for Rare Neuromuscular Disease, Sapienza University of Rome, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Current neuropharmacology [Curr Neuropharmacol] 2023; Vol. 21 (12), pp. 2543-2549.
DOI:	10.2174/1570159X21666230623094710
Abstrakt:	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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu