Novel methods for improving early and accurate diagnosis of transthyretin amyloidosis

Bakgrund: Cardiac amyloidosis is a fatal disease including light chain type and transthyrethin (ATTR) type. The ATTR might be hereditary (ATTRv) or senile (ATTRwt) and the former common in heart failure clinics, still not investigated how common. Novel therapies recently developed have emerged for transthyretin (ATTR) amyloidosis but it probably require early diagnosis.

Målsättning: The overall purpose is to develop new methods for an early diagnosis of ATTR amyloidosis. Specific aims include: A) To develope diagnostic tools based on metabolic pathways. B) To evaluate non-invasive imaging tools. C) To develop and apply a diagnostic algorithm for identifying cardiac ATTR in heart failure patients.

Arbetsplan: A) Plasma from ATTR amyloidosis patients, TTR mutation carries and healthy controls will be analysed at the Swedish Metabolomics Cente, Umeå University by gas chromatography, liguid chromatography and mass spectrometry. In addition we have a collaboration with Professor Gustav Smith to further evaluate biomarkers by using broad analysis of metabolomics and proteonomics. Furthermore, we aim to develop methods to analyze tetramer, dimmer and monomer in plasma.

B) The amyloid PET tracer 18F-flutametamol, currently used to diagnose Alzheimer's disease, will be used to characterise amyloid deposits in the CNS of patients with heriditary ATTR amyloidosis and, in the same population, we will also determine if we can visualise how to interpretate PET as non invasive diagnstic tool for ATTR cardiac amyloidosis.

C) We plan to investigate the prevalence of cardiac ATTR amyloidosis in heart failure patients selceted from the region of Umeå, using two study arms and a novel diagnostic algorithm previously evaluated in patients with hereditary ATTR amyloidosis.

Betydelse: Early diagnosis is cruical for an effective treatment of ATTR amyloidosis. We believe that our project can contribute to that by testing new and established diagnostic tools enabling early and more accurate diagnosis of all forms of ATTR amyloidosis.