Wellcome Trust Research Round-up: 22.12.14

Our fortnightly round- up of research news from the Wellcome Trust community…

Nationwide project paves way for clinical genetics diagnosis

A major nationwide project to genetically diagnose rare diseases will pave the way for translating advances in genomics into patient care in the NHS.

Deciphering Developmental Disorders (DDD), a collaboration between the Wellcome Trust Sanger Institute, the UK Department of Health and regional genetics services, is working with 12,000 families to diagnose their children’s developmental disorder, demonstrating the feasibility and value of introducing large-scale sequencing diagnostics into health care.

The project, which will continue into next year, has so far found a diagnosis for nearly a third of the first 1000 families analysed, where previous genetic tests had failed before. The diagnoses have focused on the 1100 genes that have previously been recognised as a cause of developmental disorders. This success rate will continue to improve as more disease-causing genes are discovered.

“Each of these patient families has been through a long diagnostic odyssey before taking part in the DDD project,” says Dr Helen Firth, a researcher from the Department of Clinical Genetics at Addenbrooke’s Hospital. “For many, we are able to offer the diagnosis they have waited so long for. Sometimes this improves clinical management, but simply knowing the source of the problem can provide families with peace of mind.”

Dr Caroline Wright, lead author and Programme Manager for the Deciphering Developmental Disorders project said, “the project has shown that large-scale genetic testing, which brings such enormous benefits to patients and families, is both effective and affordable.”

The DDD study will continue to recruit families until April 2015, and will continue to try to find a genetic diagnosis for all the remaining undiagnosed families. It is hoped that the approach developed in this study will be rapidly incorporated in standard clinical practice to maximise the diagnosis of rare genetic disorders.

New understanding of venom could open door to more effective anti-venoms

New research published in Toxicon, disproves the theory that venom evolved just once in reptiles, and could lead to new medical treatments to counteract snakebites.

The ‘toxicofera hypothesis’ proposed the majority of reptile species alive today, descended from a common venomous ancestor. This theory was put forward nearly a decade ago and has been widely believed, but not actually tested, until now.

Researchers in the School of Biological Sciences at Bangor University, tested the robustness of the ‘toxicofera hypothesis’ using cutting-edge DNA sequencing technology to study gene expression in the venom and salivary glands, as well as several other body tissues from a range of venomous and non-venomous reptiles.

PhD student Adam Hargreaves and his supervisor Dr John Mulley, together with colleagues at the Wellcome Trust Sanger Institute and the Institute of Biological, Environmental and Rural Sciences as Aberystwyth University, found that the toxicofera hypothesis is not supported by this study’s evidence, which suggest that venom evolved at least twice in reptiles.

This has profound implications for how the evolution of venom is understood, and also for the design of new medical treatments to counteract snakebites.

Dr John Mulley explains: “Snake venom is far simpler than was previously suggested, with the majority of venom complexity limited to just a few gene families. It seems likely therefore that we can develop more effective anti-venom treatments which focus on combatting the effects of just these families.”

New targeted drugs could treat drug-resistance skin cancer

A major new study published in Cancer Cell, reports that a brand new family of chemical compounds designed to block several key cancer-causing proteins could potentially treat incurable skin cancers. Clinical trials to test the new compounds in patients to see if they could be viable drugs, may begin as early as 2015.

Existing drugs for skin cancer- also known as melanoma- target faulty versions of a protein called BRAF, which causes about half of all melanomas, but while initially very effective, the cancers almost always become resistant to treatment within a year.

The two new chemical compounds – called panRAF inhibitors – could be effective in patients with melanoma who have developed resistance to BRAF inhibitors.

The study, published in Cancer Cell, was funded by the Wellcome Trust and Cancer Research UK, and jointly led by scientists at The Institute of Cancer Research, London, and the Cancer Research UK Manchester Institute.

The study established that for both drugs, a dose of 20mg per kg per day – which when translated to humans would be achievable by taking in pill form – caused tumours to regress without significant side-effects.

Study co-leader Professor Richard Marais, Director of the Cancer Research UK Manchester Institute, based at The University of Manchester, said “Our laboratory study showed that these new drugs deliver multiple blows to cancer by hitting several cell survival routes at once. It’s a step on from the drugs that are currently available which can’t multitask in this way.”

In other news…

Researchers at the Babraham Institute have provided the most comprehensive analysis so far of how sperm DNA is reprogrammed after fertilisation to contribute to the start of a new life.

Wellcome Trust Sanger Institute spin-out company 14M Genomics (14MG) has received £12.5 million equity financing from Syncona Partners LLP (Syncona) to develop European clinical diagnostic and treatment decision services in cancer.

Manchester University Press has published ‘The making of British bioethics’, the first open access monograph in the field of bioethics, written by Dr Duncan Wilson, Research Associate in the Centre for the History of Science, Technology and Medicine (CHSTM) and funded by the Wellcome Trust.

Dr Martyn Pickersgill, Wellcome Trust Senior Research Fellow in Biomedical Ethics, released a paper discussing neuroscience, epigenetics and social life.

A study, published in Nature Immunology, discovered a new class of highly potent antibodies from dengue-virus infected patients, which could lead to a new subunit vaccine.

Image credits: Duchenne muscular dystrophy – normal female, Wessex Reg. Genetics Centre, Wellcome Images; Painted saw-scaled viper, Echis coloratus by Todd Pierson on Flickr, BY-NC-SA-2.0; Human melanoma cell dividing, Paul J.Smith &Rachel Errington, Wellcome Images