Research Project Information
Principal researcher: Professor Ralf Schubert
Institute: Goethe University, Frankfurt
Grant award: €119,450
Project completion date: 31st May 2017
The symptoms of Ataxia Telangiectasia (A-T) can be devastating and include inflammation of the brain, a weakened immune system and an increased risk of cancer. There currently is no cure.
Stem cell transplantation is already used to help treat some cancers and diseases that lead to weakened immune systems, but is not without risk. Until now, the benefits, risks and exact protocols needed to use stem cell transplants in patients with A-T has not been studied in detail. Professor Schubert and his team carried out work to understand how a mouse model of A-T would respond to different types of stem cell transplantation.
It has previously been shown in a mouse model of A-T, that a stem cell transplant using cells donated by a healthy identical twin, stops tumours from growing and increases lifespan. It also improves the strength of the immune system. However, the likelihood of an A-T patient having an unaffected, identical sibling is very low, so the real-life benefits of this approach in the clinic are extremely limited.
Professor Schubert and his team aimed to investigate, and define a strategy for using stem cell transplants in A-T patients using cells from a genetically non-identical donor (allogenic) or those that have around a 50% genetic match (haploidentical).
They discovered that they could reduce the number of cancers in these mice, and strengthen the immune system when they were given stem cell transplants. However, when the mice were given transplants from mice that had no genetic match, there were many side effects. Many of these effects were reduced when the mice were partially ‘tissue-matched’ to the donor (haploidentical), suggesting this would be the best method to take forward into patients.
In addition, before a transplant is given a patient must undergo a series of treatments to ensure the body is ready to receive the cells and reduce the risk of any complications. The requirements of A-T patients for this have not been fully explored. Professor Schubert examined a number of different treatment types in the mouse model and was able to demonstrate one particular treatment resulted in a better survival rate and better recovery of the immune system, suggesting this would be the best option to take forward.
The project has delivered substantial data about feasibility, safety and potential success of stem cell transplant in in A-T. Whilst there are no immediate plans, the hope is that in the future these findings will form the basis of a clinical trial in children with the condition.