Action for A-T was established in 2012 by parents whose daughter Evie was diagnosed with a rare neurological condition named Ataxia Telangiectasia (A-T). The charity’s mission is simple, we aim to speed up the process of identifying a cure for A-T or treatments that delay or prevent the disabling effects of this devastating childhood condition. We do this by seeking and funding high quality peer-reviewed medical research both in the UK and around the world.
Since 2012 we have invested over £1.7million in 27 A-T related research projects globally and work closely with the research community and likeminded charities to increase our investment and maximise our impact. The charity has its own highly qualified multi-disciplinary medical advisory and peer review panel and a grant management process which has led us to achieving a best practice award from the national Association of Medical Research Charities.
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.
WHAT CAN YOU DO TO HELP?
Your support will help us to fund more vital research into this devastating condition thereby offering hope to the families who need it most. Your generous donations will be committed to ground breaking research taking place here in the UK such as the project below.
GENE REPAIR AS A POSSIBLE CURE FOR A-T Institute: School of Biological Sciences, Royal Holloway, University of London (Egham)
Our genes have a profound impact on health. In the case of Ataxia Telangiectasia (A-T), a faulty gene called ATM is responsible for the devastating course of the disease. To understand how genes like ATM work, researchers need new ways to control them. Changing genes in living cells is an extremely complex process but over recent years a new method called CRISPR has been developed that has the potential to dramatically improve the ability to edit DNA in humans. CRISPR technology allows researchers to fix a defective gene in someone who has a genetic disease by repairing the gene that is faulty and thus make a precise change to their DNA. In simple terms, CRISPR is a group of molecules that can edit DNA, fine tune them to target specific pieces of DNA, cut the DNA and insert a different piece of DNA in its place.
Professor Rafael J. Yáñez-Muñoz and his team at the Advanced Gene and Cell Therapy laboratory will use the latest CRISPR-Cas technology to test several ways of repairing the faulty ATM gene that causes A-T. They will initially work with easy-to-grow human cells in the lab, and then assess the most generic A-T gene repair strategies in human blood stem cells.
If the proposed studies are successful, follow-up projects would explore these novel gene repair methods in blood stem cells from other A-T patients with a view to facilitating clinical translation. The team will also study possible side effects of these gene repair methods. This work could eventually pave the way for a revolutionary new treatments in A-T.
These proposed strategies could lead to personalised therapies targeting individual A-T mutations in some cases, or generic A-T treatments in others. The latter could offer essentially off-the-shelf A-T treatments for most mutations. Additionally, genome editing leads to stable genetic modification and hence could be a one-off therapy, not requiring repeated administration of chemicals with potential acute or chronic side-effects.
This 24 month project begins in January 2018 and will cost £200,000. Any funds raised via the Work for Good platform will help us provide some of the consumables for this vital and potentially life changing project.