DRPLA Researchers Spotlight – Dr Jeff Carroll’s group at UW

by | Sep 13, 2023 | News Articles

It is time we created a space for our funded researchers to shine and acknowledge publicly their tremendous contributions to the field. This will be an ongoing feature in which we will introduce all our funded researchers from around the world to our readers.

The first group we want to spotlight is the one from our own Scientific Advisor, Dr Jeff Carroll at the University of Washington. Dr Carroll is a scientific researcher in the field of Huntington’s disease (HD) and a public advocate for families affected by HD. HD is caused by the same mutation type as DRPLA, a CAG repeat expansion, but it affects a different gene. Nevertheless, HD and DRPLA have some common features. Dr Carroll has been instrumental in providing scientific input to CureDRPLA and advancing DRPLA research.

Aliza Ben-Varon is a graduate student Researcher, Velvet Smith works as a Research Scientist and Bereket Gidi, an undergraduate student, has worked alongside Velvet this past year.

These three scientists have done a fantastic job of characterising a mouse model that mimics the human form of DRPLA. Using genetic engineering, scientists inserted the human ATN1 gene into mice with 112 CAG repeats so that the mice would develop DRPLA. Dr Carroll’s group have followed these mice very closely, and they have been able to observe how the mice present with ataxia (especially in the back limbs), seizures, tremors, and poor coordination. In fact, they present a severe form of DRPLA and start showing symptoms very early on.

Having a model that presents signs and symptoms that are characteristic of DRPLA is very important for scientists and drug developers. It allows them to better understand the progression of DRPLA and assess if and how a potential treatment could change the trajectory of decline.

In DRPLA, there is an accumulation of an abnormal protein in cells called ATN1, and the main therapeutic modality of interest is to reduce the levels of this ATN1 abnormal protein. Antisense oligonucleotides (ASOs) have emerged as a promising strategy in various neurodegenerative disorders because they block the ability of a certain gene to make a protein. ASOs are being tested in these DRPLA mice to determine if they can slow down or reverse DRPLA progression.

This team has been working with these DRPLA mice for over two years, and they have completed various rounds of experiments that we are hoping to share with our community in early 2024.