WHAT IS A-T?
A-T (Ataxia Telangiectasia) is a rare, genetic degenerative disease of childhood, which affects multiple systems of the human body. In people affected with A-T, a gene called ATM is mutated. The ATM gene contains the instructions for the production of the ATM protein. Thus, in A-T patients, the ATM protein is usually not produced at all, or is severely defective. The ATM protein controls many important functions in cells. A major function of ATM is orchestrating the complex response to specific types of damage inflicted on the DNA particularly by ionising radiation. Maintenance of DNA stability and integrity is critical for normal cellular life and therefore, cells devoid of ATM lack this vital defence mechanism. The nervous, immune and reproductive systems are particularly sensitive to the loss of ATM function.
WHAT ARE THE SIGNS AND SYMPTOMS OF A-T?
A diagnosis of A-T comes as a huge shock. There are no indicators at birth and most children with A-T appear ‘seemingly healthy’ in line with their peers during the first year of life. The first signs of A-T are neurological: poor balance and reduced motor coordination (ataxia) being the most prominent, where children are often described as ‘wobbly’. Other signs that follow are deterioration of motor skills, involuntary movements, abnormal eye movements, and difficulty with speech. Further features that may affect some children are insulin-resistant diabetes, premature greying of the hair, difficulty swallowing, drooling and slowed growth. The severity and range of symptoms vary in individual patients.
HOW DOES THE DISEASE PROGRESS?
Research on ‘why’ and ‘how’ the disease progresses continues, as does research into ATM and ATM-related processes. We know that as a child gets older, some types of cells in the central nervous system (CNS) start to die. The patients lose neurons, particularly in a part of the CNS called the “cerebellum”, which controls fine motor coordination. This degeneration in the cerebellum is the prime cause of the progressive neuromotor dysfunction of A-T patients.
HOW DOES A-T AFFECT THOSE DIAGNOSED?
Health progressively deteriorates causing an overall loss of coordination and muscle control. Children are usually confined to a wheelchair by the second decade of life (around the age of 10) and will need assistance with everyday tasks. Children often lose their ability to write, speech becomes slower or slurred and reading becomes problematic due to difficulty in eye movement control. A-T does not affect the mind. There are no learning difficulties linked to having A-T, and affected children and adults are neither intellectually nor socially impaired.
A-T patients are also predisposed to developing cancer (in particular, acute lymphocytic leukemia or lymphoma) and their immune system is weakened. Thus, many of them are susceptible to recurring respiratory infections. A-T is also characterised by telangiectasias (widened, “spider” like veins), which often appear in the corners of the eyes. Due to their inability to respond properly to specific types of DNA lesions, A-T patients also exhibit extreme sensitivity to ionising radiation, such as X-rays.
Life span is shortened, usually by respiratory failure or cancer. A-T is life-limiting, with those affected generally living until their twenties. There is currently no cure for A-T and no treatments to slow down or stop the progression of this devastating disease.
RESEARCH STRATEGY 2020 – 2025
Our mission is simple, we aim to fund medical research to speed up the process of identifying a cure for Ataxia Telangiectasia (A-T) or treatments that delay or prevent the disabling effects of this devastating childhood condition. Our vision is a future where the effects of A-T are minimised, and lives are transformed.
Achievements to date
Action for A-T was established in 2012 by two parents who identified a need for more A-T medical research to be funded in the UK. Since then, we have focused on developing processes which make the most effective use of our funds and resources, to ensure we only support the best science. To date we have:
– Established links with the global A-T research community;
– Developed partnerships with other charities to collaborate on research projects
– Established an expert scientific committee
– Developed a robust application, peer review and grant management process
– Invested £3.1 million in 40 A-T projects around the world
– Exponentially increased our portfolio of UK-based projects from zero to > 50%
– Confirmed our status as the largest funder of A-T research in Europe
In addition to supporting and funding research aimed at improving the understanding of A-T, there are many innovative and exciting medical research opportunities that raise the prospect of real progress in combating the effects of genetic conditions such as A-T. We are committed to doing all we can to maximise these opportunities and will focus on the following key areas for the next five years:
- Fund research that will have the greatest impact
We will consider supporting research which aims to advance our understanding of the underlying mechanisms that lead to A-T, identify interventions which will stop or slow down the progression of the condition as well as finding ways to repair the damage done by the disease or develop treatments that relieve and ultimately cure symptoms. Although we aim to have a balanced portfolio, we are particularly interested in pursuing basic science or translational research projects in relation to two areas that have the potential to achieve the greatest benefits for children and adults living with A-T:
‘UNDERSTANDING’ THE DISEASE
The most devastating effect of A-T is on the nervous system. The progressive neurological deterioration experienced by children causes the most disabling effects on their lives. Despite advances in knowledge, it is not completely understood what processes are taking place in those who have A-T and why the condition is progressive. Understanding exactly what happens to the structure, function and development of the brain and the immunology of the disease will provide clues that could lead to the development of new therapies.
‘IMPROVING’ SYMPTOM MANAGEMENT
A-T is a complex condition with a range of symptoms; mortality rates are high in those affected largely due to lung infections and the development of cancer. Determining the mechanisms that lead to lung failure and cancer in A-T patients, developing improved ways to prevent, manage and optimally treat lung symptoms and cancer would be of significant benefit to A-T patients.
- Focus on a collaborative approach
We will continue to focus on collaboration and partnerships. We strongly believe in pooling resources and funds as this approach is key to accelerating the pace of research. It also helps us maximise our limited funds and achieve more than we could on our own. We want to avoid unnecessary duplication of efforts wherever possible and strive for an international effort that is coordinated. We will continue to encourage and support networking opportunities in the A-T community and work alongside others wherever possible.
- Build capacity in the UK
We will seek out talented research leaders across all disciplines relevant to A-T whilst continuing to build capacity and increase the amount of research projects based here in the UK. The community of A-T researchers in the UK is very small in comparison to the burden of disease. This in part is due to A-T being a rare disease, but Action for A-T believe more can be done. We aim to build a community of A-T research leaders and increase the amount of research that is taking place here in the UK. Although we will always fund the highest quality applications wherever they are from; our key focus is to invest in projects and people based in the UK.
*This strategy was published 1st March 2020