FRRB Project 1751723 - Genetic modifiers of hereditary and acquired ATTR amyloidosis

Name and Surname of PI

Andrea Cortese

Project Acronym


Project ID


Host Institution

Fondazione Istituto Neurologico Casimiro Mondino - Pavia

Pathology of Interest

ATTR amyloidosis

Research Area

Rare Diseases

Project Start Date

1 June 2021

Project End Date

31 May 2024


€ 555.000,00

Type of Project



Hereditary transthyretin (ATTRv; v for variant) amyloidosis is a rare genetic systemic disease caused by mutations in the transthyretin (TTR) gene. Mutant TTR protein tends accumulate across different tissues and organs, especially peripheral somatic and autonomic nerves and heart. This is a progressive, disabling and life-threatening condition with a mean survival of 4.7 years from diagnosis, if left untreated. Despite major advances in its diagnosis and treatment, the factors impacting on the disease onset and progression are still largely unknown. The primary objective of this study is to identify in ATTR amyloidosis genetic modifiers of onset, penetrance, disease severity and progression.

During the second year of the study, we have collected DNA from ~3000 patients affected by hereditary or acquired TTR amyloidosis. The study now involves 50 centres from 19 countries and 4 continents. We have finalised the design of the custom content of the arrays which are being now manufactured and we have further optimised the long-read sequencing technique for the analyses, which will take place during the last year of the study. The achievement of the important goals described above will enable us, during the last year of the study, to test the patients’ DNA in order to try to identify the genomic regions which can modify, either improving or aggravating, the disease phenotype. If successful, the study may lead to the identification of novel druggable targets.


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