Validation of protective mutations for diseases related to transthyretin

The Bioinformatics CRO, Inc.

Lay summary

Misfolding of the protein encoded by the transthyretin (TTR) gene, resulting in long fibrils of amyloid protein, has been implicated in a variety of diseases, ranging from amyloid transthyretin amyloidosis to cardiovascular disease. We aim to assess the ability of mutations known to stabilize the TTR protein to protect against these diseases, or to confer prolonged survival for them. We also will examine other mutations known to impact TTR expression levels and function.

While there are contradictory studies of one of these mutations, these studies did not use exactly the same analytical methods. We aim to use the same analytical methods, and also to subset to the higher risk older populations within the data, to get a more complete picture of how stabilizing TTR mutations affect risk of TTR-related diseases. We will test if people with these putatively protective mutations are less likely to develop TTR-related diseases, and if people with these mutations who do develop these diseases have longer survival.

We anticipate the project duration to be 24 months. This research is in support of a drug discovery program that, if successful, would result in treatments for patients with TTR-related diseases.