Circulating microRNAs Profile in Patients With Transthyretin Variant Amyloidosis

Abstract

Transthyretin variant amyloidosis (ATTRv) is a rare autosomal dominant disease characterized by the accumulation of amyloid in many organs, mostly causing a sensory-motor neuropathy, cardiomyopathy, and dysautonomia. The aim of the study was to report microRNAs (miRNAs) expression profile identified in the blood of ATTRv patients. Ten ATTRv patients, 10 asymptomatic carriers of transthyretin variant (TTRv), 10 patients with Charcot-Marie-Tooth (CMT) disease, and 10 healthy controls were studied. Human Schwann cells cultures were used to study the regulatory effects of miR-150-5p on the expression of cAMP response element-binding protein (CREB), brainderived neurotrophic factor (BDNF), and nerve growth factor (NGF). ATTRv patients had 33 miRNAs up-regulated and 48 down-regulated versus healthy controls; 9 miRNAs were up-regulated and 30 down-regulated versus CMT patients; 19 miRNAs were upregulated and 38 down-regulated versus asymptomatic TTRv carriers. Twelve out of the 19 upregulated miRNAs had a fold increase higher than 100. The validation experiment indicated miR-150-5p as a valuable biomarker to differentiate ATTRv patients from asymptomatic TTRv carriers (AUC: 0.9728; p < 0.0001). Schwann cells culture model demonstrated that miR-150-5p is a powerful negative regulator of CREB, BDNF, and NGF genes. Identification of deregulated miRNAs can help in understanding the complex pathomechamism underlying the development of ATTRv and related multisystemic pathology. Further investigations are needed on the role of circulating miR-150-5p to predict the shift of TTRv carriers from an asymptomatic status to symptoms appearance.

Patisiran in hATTR Amyloidosis: Six-Month Latency Period before Efficacy

“…While the exact clinical phenotype depends on the underlying mutation, cardiomyopathy, peripheral polyneuropathy, and autonomic neuropathy with orthostatic hypotension and gastrointestinal dysautonomia are common [ 9 ], and the previously used definition of Familial Amiloidotic Cardiomyopathy (FAC) or Familial AmiloidoticPolineuropathy (FAP) have become outdated [ 10 , 11 ]. The necessity to monitor disease progression has recently led to an increase of the research on new biomarkers [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ], with the particular aim to record the shift from asymptomatic to symptomatic stage, whichcould allow physicians to start specific treatment for hATTR amyloidosis.…”

Advances in Treatment of ATTRv Amyloidosis: State of the Art and Future Prospects

“…Future studies are needed to determine if an earlier initiation of treatment would be able to improve the clinical course of the disease. For this aim, new biomarkers can help in monitoring the shift from asymptomatic stage to stage 1 [ 79 ].…”

A Review on the Evolving Roles of MiRNA-Based Technologies in Diagnosing and Treating Heart Failure

“…To date, the function of this miRNA remains poorly characterized and it is not tissue-specific. Serum miRNA expression profiling has been performed in patients with ATTRm: comparing miRNA expression profiles between hereditary ATTR patients (presenting with typical symptoms, such as neuropathy and CMP) with asymptomatic ATTRm carriers, the authors identified miR-150-5p as a potential biomarker to differentiate ATTRm patients from asymptomatic TTR carriers (AUC: 0.9728; p < 0.0001) [12]. Of note, recently, as a major advancement in the field of RNA-based technologies, TTR is one of the first diseases for which RNA-based therapeutics have been approved (polyneuropathy in ATTRm) [47,48].…”