Adrestia Therapeutics co-founds research consortium to tackle ataxia telangiectasia

Adrestia Therapeutics has co-founded a research consortium to find new treatments for the fatal neurodegenerative disorder ataxia telangiectasia (AT).

Prevalence of the inherited and progressive condition, which is typically diagnosed in young children, is thought to be underestimated, with an estimated 3,000 undiagnosed cases in the US alone.

It is primarily driven by mutations in the ATM gene, which is involved in DNA damage repair.

Babraham Research Campus-based Adrestia has joined with the A-T Children’s Project, the AT Society and Action for AT to find disease-modifying drugs for patients.

The company will deploy its pioneering synthetic rescue expertise - an approach to treating genetic disease that involves modulating a related pathway to correct the effects of the mutation and ‘rescue’ cells from disease.

Adrestia CEO Robert Johnson said: “The entire Adrestia team is moved by the dedication of the AT community and we are honoured to be working closely with our consortium partners to combine patient networks, scientific and other resources to accelerate the development of new treatment options, for which there is a desperate need.

“Many genetic diseases are untreatable with current technologies. The power of our synthetic rescue approach lies in its ability to reveal alternative therapeutic targets which lie outside the core biological pathway.

“Our ultimate goal is to develop effective medicines which rebalance the underlying biology, unlocking new ways of treating intractable genetic diseases.

“AT and several related conditions are caused by an inability to repair DNA damage normally. We believe the same synthetic rescue targets may be useful for a range of common diseases which also involve DNA damage repair defects.”

Adrestia is using its technology to mine systematically the human genome for novel targets that could be used as the basis for therapies for AT and related diseases. No corrective therapies currently exist for AT, which can have varied effects. The AT Society, a UK charity that is currently the subject of a BBC Lifeline appeal, says the three most obvious it affects people are by:

• impairing the functioning of the cerebellum and other parts of the brain, leading to increasing problems of coordination and movement;
• weakening the immune system, reducing the ability to fight off infections; and
• significantly raising the risk of cancers, particularly lymphoma and leukaemia.

Prof Penny Jeggo, a renowned DNA damage researcher and AT Society trustee, said: “AT has a devastating impact on families around the world and despite its severity and the clear understanding of its primary cause, we still cannot change the course of the disease. We welcome innovative approaches that can move us towards treatments or cures.”

And Brad Margus, founder and board chair of the US-based A-T Children’s Project, who has two sons with the disease, added: “We are proud to begin this new initiative with Adrestia as we drive towards a brighter future for our community.”

Sean Kelly, chief executive of Action for AT, a charitable funder of medical research, said: “As a group deeply involved with advancing therapeutic research, we know collaboration and medical innovation are the path to a future where the effects of AT are minimised.

“We are proud to join this consortium and support a new line of promising research alongside other tireless advocacy groups.”

There is a wealth of human genetic data demonstrating that defects in DNA damage repair - the root cause of AT and related conditions - also drive a range of common chronic diseases, covering neurodegeneration, immune dysfunctions, cardiovascular disease, diabetes and metabolic diseases.

Adrestia was co-founded by Cambridge’s Prof Steve Jackson, an expert in DNA damage repair biology whose work led to Olaparib - the first approved cancer drug to exploit DNA damage repair mechanisms via synthetic lethality.

The creation of that drug - now a blockbuster - has paved the way to applying complementary principles to discover new drugs for genetic diseases.