Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis

Recent advances in genetic testing have allowed for pathogenic mutation identification in
family members of affected individuals prior to onset of symptoms. While the presence of
mutation and the corresponding TTR kinetic stability have been directly linked to disease
development, the molecular drivers of tissue specific degeneration have not been defined. We
hypothesize that soluble misfolded TTR oligomer species may be circulating within the blood
of these patients possibly years prior to amyloid deposition and could serve as an early
biomarker and/or driver for disease development. In this line, The Scripps Research Institute
has developed a peptide-based probe that specifically labels and integrates into misfolded
TTR oligomers allowing the relative circulating concentration in the bloodstream to be
determined. Longitudinal monitoring of untreated, asymptomatic TTR amyloid genetic carriers
utilizing the Scripps probe is likely to provide novel insight into early disease
progression. We also plan to utilize the Scripps probe to monitor disease progression in TTR
amyloid genetic carriers currently undergoing treatment by observing how treatments affect
the circulating misfolded TTR oligomers. Through enhanced understanding of early disease
progression and treatment efficacy, our hope is to limit amyloid accumulation in cardiac and
nerve tissue and delay the development of the invariably fatal TTR amyloid
cardiomyopathy/neuropathy.

Inclusion Criteria:

- Patients with known hereditary ATTR amyloidosis genetic mutations as identified by
genetic testing.

Exclusion Criteria:

- Patients with ATTR amyloidosis identified as wild-type.