Developing a new model for testing drugs to treat Ataxia Telangiectasia

Research Project information

Principal researcher: Professor Richard Gatti
Institute: University of California, Los Angeles, USA
Grant award: $129,318 (managed by Sparks)
Project Completion Date: December 2015

Project Overview

Professor Gatti and his colleagues are aiming to develop a class of drug called “read-through compounds” to treat A-T. These drugs target one specific class of mutation in the ATM gene (the gene that carries a mutation in A-T) called a nonsense mutation. This is when one letter of the DNA sequence code is changed to another letter thereby creating a STOP signal in the middle of the gene.

Read-through compounds encourage the cells to ignore this STOP signal so they will start to produce the ATM protein in a similar way to healthy cells. The aim of this project was to develop a new mouse model that carries a nonsense mutation in the ATM gene. In order to fully investigate if these drugs might be effective in A-T and safe for clinical trials, they will need to be tested in animal models of A-T. This new mouse strain will be used for other A-T research as well.

Project Outcome

The team have completed the first steps in developing a mouse colony of ATM mice that carry a nonsense mutation.   They have carried out some preliminary testing of a number of read-through compounds in these models and as they continue to build the mouse colony, will be able to fully test these and other compounds for their effectiveness at reducing the A-T symptoms that the mice possess.  Read-through compounds could also have similar beneficial effects in other genetic conditions that are caused by a nonsense mutation.  Thus, with just a few drugs that can read through nonsense mutations, patients with many genetic diseases may hope to benefit.

Publications

The team plan to publish the details of developing the new mouse strain along with its usefulness for evaluating drug candidates.  This would be expected to occur in 2017-18.

What Next?

The next steps of this project will be the identification and evaluation in the mouse model of potential read-through drugs. As there are currently no effective treatments or cures for this condition, this could represent a significant step forward for nearly a third of the families who are living with A-T.