Hereditary Transthyretin Amyloidosis with Polyneuropathy
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Variant transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, progressive multisystem disorder caused by pathogenic variants in the transthyretin (TTR) gene. Primarily characterized by polyneuropathy, the disease results from amyloid fibril deposition in the endoneurium, which leads to progressive sensory, motor, and autonomic impairments. ATTRv-PN exhibits significant clinical heterogeneity driven by genotype-phenotype correlations, complicating diagnosis—especially in nonendemic regions. Early recognition through genetic testing, advanced imaging techniques, and tissue biopsies is essential to initiate timely treatment and improve patient outcomes. The therapeutic landscape has advanced considerably with the development of TTR stabilizers, such as tafamidis and diflunisal, which slow disease progression by preventing TTR tetramer dissociation. Moreover, gene‐silencing therapies—including patisiran, vutrisiran, inotersen, and eplontersen—target TTR mRNA to reduce amyloid formation and have demonstrated substantial efficacy in clinical trials. These treatments improve neuropathy progression, quality of life, and survival, particularly when initiated early. This review emphasizes the critical importance of early detection, personalized treatment strategies, and ongoing research into innovative therapies to address the unmet needs of patients with ATTRv-PN. Continued advances in diagnostic tools and therapeutic approaches hold promise for significantly improving prognosis and quality of life for affected individuals.
Abstract
Variant transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a rare, progressive multisystem disorder caused by pathogenic variants in the transthyretin (TTR) gene. Primarily characterized by polyneuropathy, the disease results from amyloid fibril deposition in the endoneurium, which leads to progressive sensory, motor, and autonomic impairments. ATTRv-PN exhibits significant clinical heterogeneity driven by genotype-phenotype correlations, complicating diagnosis—especially in nonendemic regions. Early recognition through genetic testing, advanced imaging techniques, and tissue biopsies is essential to initiate timely treatment and improve patient outcomes. The therapeutic landscape has advanced considerably with the development of TTR stabilizers, such as tafamidis and diflunisal, which slow disease progression by preventing TTR tetramer dissociation. Moreover, gene‐silencing therapies—including patisiran, vutrisiran, inotersen, and eplontersen—target TTR mRNA to reduce amyloid formation and have demonstrated substantial efficacy in clinical trials. These treatments improve neuropathy progression, quality of life, and survival, particularly when initiated early. This review emphasizes the critical importance of early detection, personalized treatment strategies, and ongoing research into innovative therapies to address the unmet needs of patients with ATTRv-PN. Continued advances in diagnostic tools and therapeutic approaches hold promise for significantly improving prognosis and quality of life for affected individuals.