Stopping the development of harmful T-cells - a new approach to treating rheumatoid arthritis

Disease - Rheumatoid arthritis

Lead applicant - Miss Joy Ogbechi

Organisation - University of Oxford

Type of grant - Foundation Fellowship

Status of grant - Active

Amount of the original award - £189,950.84

Start date - 10 April 2017

Reference - 21434

Public Summary

What are the aims of this research?

T-cells are white blood cells that play various important roles during an immune response. In rheumatoid arthritis, the activity of T-cells which mediate joint damage is elevated, while the activity of those that prevent these harmful immune responses (regulatory T-cells) is suppressed. The researchers aim to stop the development of harmful T-cells, hoping this method will treat the disease.

Why is this research important?

Current treatment options for rheumatoid arthritis are limited in their ability to achieve long-term remission. Restoring normal T-cell function is crucial to this because it will stop the effects of harmful T-cell such as joint damage. To date, studies have either looked to enhance regulatory T-cell responses or inhibit harmful T-cells. This study will combine the benefit of these individual approaches, with the aim to achieving long-term remission of the disease.

Unlike regulatory T-cells, harmful T-cells require amino acids (the building blocks of proteins) for their development. This study proposes a new approach to treating rheumatoid arthritis by investigating the benefit of starving developing T-cells of the amino acids they need, in order to selectively obstruct harmful T-cell development, and instead forcing them to become regulatory T-cells.

The research will involve looking at a number of amino acid transporters in human T-cells to identify those that can be targeted to stop the development of harmful T-cells. Once the best transporter has been identified, the researchers will investigate its role as a potential drug target by using mice with arthritis. The selected amino acid transporter will be inactivated in mice, to allow the team to look at the effect that this will have on disease progression and severity.

How will the findings benefit patients?

Stopping the development of harmful T-cells and promoting regulatory T-cells could have the potential to stop joint damage and reduce the development of other symptoms associated with rheumatoid arthritis. In the short term this project could lead to the identification of new molecules that could be targeted by drugs, for the treatment of the disease, a key initial step in the process of drug discovery and development. In the long term, it could result in the development of better drugs for rheumatoid arthritis treatment.