Introduction

Hello and welcome all! I am excited to share with you what I will be researching over the next few months.

My Senior Research Project is focused on a rare, genetic disease called Transthyretin (TTR) Amyloidosis. This disease occurs due to point mutations in the 127-amino acid protein transthyretin, leading to the creation of abnormal proteins called amyloids, or amyloid fibrils, which can be deposited in any organ or tissue. Most commonly, amyloid fibrils are deposited in the brain, kidneys, and heart. Transthyretin amyloidosis affects approximately 8,000–10,000 people around the world; specifically in areas such as Portugal, Sweden, and Japan, which are known as endemic regions.

There are three forms of transthyretin amyloidosis: neuropathic, leptomeningeal, and cardiac. Specifically, the cardiac form of transthyretin amyloidosis affects the heart. Individuals with cardiac transthyretin amyloidosis may have arrythmia, orthostatic hypertension, or cardiomegaly. This happens from amyloid fibrils invading the myocardium, the muscle tissue of the heart. The invasion leads to diastolic dysfunction, a decline in performance of one of the ventricles of the heart. Diastolic dysfunction can cause restrictive cardiomyopathy to occur, which ultimately leads to symptomatic heart failure.

Unfortunately, while treatment options exist for this disease, there is no cure. The disease is an autosomal dominant disorder where over 120 different mutations may be present in transthyretin. However, not everyone who carries a mutation in the TTR gene will develop this disease and the reason why some people do not develop the disease is not known. 

My research question focuses on why some ethnicities, like African American or Portuguese, develop this disease and if possible, develop a more efficient treatment option for these afflicted individuals.