Central nervous system involvement in two siblings affected by hereditary transthyretin amyloidosis 30 years after liver transplantation: a model for gene-silencing therapies.
Andrea Di PaolantonioA RomanoV GuglielminoF VitaliM A SciarroneG BisogniT VerdolottiM MaceroniA M MinnellaM LuigettiPublished in: Neurological research (2023)
Hereditary transthyretin amyloidosis (ATTRv) is a genetic, autosomal dominant, severe disease characterized by progressive sensory-motor polyneuropathy, cardiomyopathy, dysautonomia, renal and eyes involvement, provoked by the deposition of the mutated and unstable transthyretin protein. In past decades, liver transplant, avoiding the synthesis of the pathologic protein, has been a good, even if not resolutive, treatment. In this report we describe two siblings affected with ATTRv, who developed first symptoms of disease at a young age and underwent a liver transplant with prompt resolution of clinical manifestations. After several years, central nervous system and eyes symptoms relapsed despite treatment, considering that the synthesis of mutated protein continues in choroid plexus, a locum where current therapies are unable to act. In our opinion, these cases represent a long-term prognostic model for the novel gene-silencers approved for ATTRv, because they share a similar therapeutic effect with liver transplant: the block of mutated protein synthesis limited only in the main transthyretin (TTR) production organ is able to prevent the progression of disease only for some years, but not to avoid long-term clinical worsening due to extra-hepatic production of TTR. Novel future therapeutic strategies are demanded to guarantee a better long-term stabilization of symptomatology.
Keyphrases
- wild type
- optical coherence tomography
- multiple myeloma
- heart failure
- binding protein
- protein protein
- amino acid
- genome wide
- cerebrospinal fluid
- multiple sclerosis
- acute lymphoblastic leukemia
- small molecule
- ultrasound guided
- gene expression
- transcription factor
- dna methylation
- lymph node
- radiation therapy
- early onset
- replacement therapy
- combination therapy
- locally advanced