Effect of TTR Gene Therapy in Alzheimer's Disease
A protein called TTR will be studied to find out whether it can be used to treat people with Alzheimer’s Disease (AD). TTR has been shown to have an effect in mice who show symptoms like those of AD in humans. It is unknown whether TTR will have an effect on the disease in humans as well. Different types of TTR, where it is given, and when it is given will be studied.
The protein transthyretin (or TTR) has been shown to have an effect in mice who have symptoms like those of Alzheimer's Disease (AD) in humans, but it is unknown whether TTR will have an effect on the disease in patients as well. I am using adeno-associated virus (AAV), a safe and non-pathogenic type of virus, to deliver TTR to a mouse model of AD and study its potential effect on disease modulation. Our studies will investigate when and where expression of TTR can have a beneficial impact
If our hypothesis proves to be successful in halting disease progression, we will continue our line of research towards a better understanding of how TTR ameliorates AD progression beyond Aβ deposition and understanding the mechanistic relationship between the two proteins. These studies will be necessary to advance this approach to a potential clinical application.
About the Researcher
My research interests focus on finding the mechanisms of neurological diseases and developing strategies for treatment. As a graduate student, I established animal models of familial amyloidotic polyneuropathy (FAP) through vascular delivery of AAV8 vectors encoding transthyretin (TTR) V30M, which is a common mutation in FAP patients. Throughout my PhD, I also studied a gene therapy approach to FAP using an AAV-driven expression of a stable TTR variant (T119M) found in compound heterozygote patients with a milder phenotype. During my training, I became fascinated with the mechanisms of amyloidotic diseases. In the particular case of Alzheimer’s disease, the fact that there’s still so much to learn and so many factors that can influence its progression, drives my scientific curiosity to make an impact in patients’ lives. My combined background in TTR biology and in design and production of AAV recombinant vectors, as well as molecular and biochemical techniques, will allow me to investigate the potential role of TTR in Alzheimer’s and its influence in disease progression.
Growing up in Portugal I knew since early that being a Medical Doctor was not something for me. Instead, I always knew that my way to help people was going to be through science and research, working behind the hospital. In my PhD I pursued a gene therapy treatment for a form of peripheral amyloidotic disease. My training taught me about amyloidosis and triggered my curiosity about Alzheimer's Disease. During my postdoc training, I've been learning more about gene therapy and molecular biology techniques, and although applying it to rare diseases, I've always kept in mind that we still don't know exactly what causes AD and what we can do to treat this disease. With this award I hope to start my career as an independent scientist and establish myself as a researcher in the field of gene therapies for AD.
First published on: July 10, 2019
Last modified on: August 27, 2019