Transthyretin amyloidosis (ATTR) is a rare, progressive, and ultimately fatal condition characterized by the abnormal extra cellular deposition of transthyretin (TTR) protein within the peripheral nerves (ATTR-PN) and/orwithin the heart (ATTR-CM). There are two types of ATTR: (1) hereditary ATTR (hATTR), where the destabilizing mutation in the TTR-gene is inherited, or (2) ATTRwt, in which people with the wild-type TTR-gene sequencedevelop the disease sporadically. Recent estimates put the worldwide number of people affected by ATTR atapproximately 550,000. However, these patient populations are thought to be significantly underdiagnosed, asthere is a lack of rapid and readily available diagnostics.New diagnostics for ATTR disease are needed as confirmation of ATTR is slow, taking up 5 years. Many patientspresent with symptoms that can be attributed to other conditions, leading to misdiagnosis. Due to this, ATTR isoften diagnosed by process of elimination of other diseases and many patients have to see multiple specialistsbefore getting the correct diagnosis, causing a delay in treatment and further amyloid deposition. Given that thelife expectancy once diagnosed with ATTR is only 2-10 years, a blood-based diagnostic and biomarker could beused to shift the current paradigm from confirmation of late-stage deposition to a clinical level screen, allowingan individual with suspected risk to receive disease-modifying treatment earlier, reducing mortality, andimproving patient quality of life. Furthermore, a diagnostic biomarker will be invaluable in determining the efficacyof drugs for treatments which have been shown to have variable long-terms outcomes for patients. This will allowphysicians to guide patients to the most cost effective and appropriate approved drug therapies for theircondition.The path from normal TTR to amyloid deposition proceeds through a monomeric intermediate which can be abiomarker of disease risk and progression. The proposed blood-based diagnostic is designed specifically todetect the TTR monomer using novel, ultra-rare antibodies that have been discovered and will be rapid, sensitive,and non-invasive. In Phase 1, initial proof-of-concept data will be generated to show that there is elevated TTRmonomers in patients diagnosed with ATTR compared to normal, healthy donors. If successful, this will be thefirst step towards the commercialization of the first blood-based diagnostic for the disease.
Public Health Relevance Statement: NARRATIVE
Transthyretin Amyloidosis is a rare and fatal condition which is difficult to diagnose with limited, expensive, and
only moderately-effective treatment options. We propose to develop an inexpensive and rapid diagnostic tool to
be deployed as a part of clinical level medical screenings in order to diagnose this condition earlier, allowing for
potentially improved treatment outlooks, and to monitor treatment status in diagnosed patients.
Project Terms:
