In the news

Researchers using the new sequencing technology, RNA-seq, have created a detailed map of the mouse brain, laying the ground for developing existing maps of the human brain (see previous news). The genome-wide atlas, the result of a collaboration between the US’s National Human Genome Research Institute and Oxford University, provides unprecedented detail of over 11,000 genes across the six layers of the mouse cerebral cortex. In humans this is the region responsible for memory, sensory perception and language.

The map shows that gene activity may vary across different layers, suggesting areas where specific genes, for example those connected to Parkinson’s or Alzheimer’s, play important roles.“These are correlations, not necessarily causal”, said T. Grant Belgard, lead author of the published paper “but they do suggest directions for future research.” Next year, Belgard and others will attempt to replicate the mouse brain atlas for parts of the human brain. The new resource is freely available at http://genserv.anat.ox.ac.uk/layers 

The US Patent and Trademark Office has granted a patent covering the technologies used in the production of induced pluripotent stem cells (iPSCs).

These cells are important for stem cell and regenerative medicine research and development, and are considered by many to be a useful and ethically acceptable alternative to human embryonic stem (HES) cells, though the properties of the two forms of cell are not identical.

This includes two key methods of iPSC production, both involving the insertion of specific genes into somatic cells.These technologies were developed by Japanese researcher Shinya Yamanaka at Kyoto University; Kyoto and the related iPSA Academia have previously made an agreement to patent pooling with company iPierian (see previous news).

The development is good news for Kyoto, despite already holding patents in Japan and Europe, thanks to the size of the potential market in the US. The US patent is also broader than the Japanese one, including additional genes similar to those used in iPSC production, although the European patent granted last month is reportedly broader still, including products created by the iPSC production technology genes. 

A new phase II UK drug trial is underway for patients with advanced hereditary breast-ovarian cancer, which arises from mutations in the BRCA1 and BRCA2 genes. 

Funded by Cancer Research UK and the Oxford Biomedical Research Centre, the study will examine the effect of the thiopurine cancer drug 6-mercaptopurine on cancer cells with BRCA mutations. Previous research has shown that other drugs such as PARP inhibitors can target such cells effectively (see previous news), but patients can develop resistance to these treatments. 

Trials of personalised (or more accurately, stratified) medicines targeted specifically at specific sub-populations of patients will become increasingly common in coming years, especially in cancer. The drug vemurafenib (PLX4032) has just been approved in the US for the treatment of advanced melanomas that have mutations in the BRAF gene (see previous news). 

The US Food and Drug Administration (FDA) has issued a new strategic plan that aims to drive translation of science into health by streamlining product development and improving patient outcomes. 

The Strategic Plan for Regulatory Science is intended to allow the regulator to ‘make science based decisions resulting in sound regulatory policy’ and foster innovation, by improving the processes by which new products from research in areas including genomics, personalised medicine, cellular and gene therapies. This includes developing new ways of assessing novel therapies and technologies, drawing on multi-disciplinary expertise, as well as facilitating the development of treatments for ‘special populations’ such as patients with rare or neglected diseases.  

New guidance on making applications for the approval of genomic, proteomic, and imaging-based biomarkers, and on how medical device applications are assessed (including consideration of the companion diagnostics) has also been released by the regulator this month.

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Researchers at the University of Hong Kong's Faculty of Medicine are to conduct a major study of more than 30,000 Chinese people in an attempt to identify genes that cause high cholesterol.

Rising cholesterol levels and associated cardiovascular disease are a significant public health problem in China. The new study will involve over 30,000 people from Hong Kong and Guangdong province in southern China who have had regular health and cholesterol checks over recent years. In addition to identifying genes associated with high cholesterol levels, the researchers also plan to examine how far they match such genes in Western populations, and how effective common statins (such as Pfizer's Lipitor, AstraZeneca's Crestor and Merck & Co's Zocor) are in people with different genetic profiles. 

The researchers say that statins, widely used to reduce cholesterol levels in many countries, are generally much less effective among southern Chinese populations. This study may indeed reveal genetic differences that account for this and could direct the development of new forms of cholesterol-lowering drugs that work better. This would be a prime example of population-level stratified medicine in action. 

The release of a new biobank of genetic and medical information could significantly aid our understanding of the genetic and environmental influences on health and ageing. US healthcare providers Kaiser Permanente and the University of California, San Francisco have completed the first phase of a project to collect and analyse the genomes of 100,000 people ranging in age from 18 to 107 (see previous news). 

As well as holding one of the most comprehensive sets of information available the Kaiser database is unusual in its focus on individual medical histories, rather than specific disease. Participant data such as blood-test results, prescriptions, and other conditions could help researchers draw a better picture of how genetics influences a broad range of disorders - for example, blood pressure and the effectiveness of medication. It also includes environmental data, such as air and water quality.

Cathy Schaefer, executive director of the Kaiser Permanente Program on Genes, Environment, and Health, and a co-leader on the project said: “we think some of the most interesting initial questions will relate to aging". The project has an average participant age of 65 and contains data from the worlds’ largest telomere study. Researchers will continue to follow participants as long as they continue to receive health care from Kaiser allowing them to examine, for example, how accurately telomere length can predict longevity or healthy ageing (see previous news).  The database will soon be available to the wider scientific community.

A new report has revealed that efforts to reduce cases of neural tube defects (NTDs) in Europe have made little headway.

NTDs (spina bifida, encephalocele and anencephaly) are severe forms of birth defect that may be incompatible with life or cause serious disability. However, up to 70% of cases can be prevented by ensuring that women receive adequate dietary intake of folic acid before conception. The second annual report on NTD prevention in Europe from the International Federation for Spina Bifida and Hydrocephalus has found that cases have hardly declined in the last twenty years – more than 4,500 pregnancies are affected each year across Europe, of which it is estimated that 72% are terminated.

The report calls for policy makers to take prompt action to address this problem, noting that existing policies fail to recognise that around half of all pregnancies in Europe are unplanned and that the impact of pre-conceptual medical advice is therefore limited. Instead, the report proposes that countries adopt WHO recommendations on folic acid intake in women of childbearing age and explore new ways of communicating effectively to these women, including via health and sex education in schools.

Comment: The need to adopt realistic approaches to public health problems is highlighted here; even in well-resourced countries, there is apparently more to be done to encourage the use of simple preventative measures against these common and very serious forms of birth defect.

A new report from the UK Human Genetics Commission (see previous news) examines the impact of DNA patenting on innovation and development and calls for national action.

Intellectual Property and DNA Diagnostics is the product of a 2010 seminar focused on common concerns surrounding intellectual property (IP) issues related to DNA and biomarkers, notably that patents may impede research, development provision and quality of genetic tests for medical purposes. However, lack of financial incentives (in the form of IP protection) for commercial investment in developing DNA diagnostics was shown to be a barrier to innovation. 

The report calls for a forum to be set up to gather independent evidence on the impact of biomarker IP on diagnostic innovation. It recommends that the UK government should establish ‘a biomarker IP monitoring function’ and support national implementation of ‘ways to manage biomarker IP issues’, and also suggests that the UK research councils should review their guidelines on licensing patents.

Comment: The report (which draws on a 2003 report on intellectual property rights and genetics from the PHG Foundation) notes that DNA and biomarker patents currently form a crucial element for both commercial and increasingly also academic researchers in securing financial investment in research and development. This perspective was mirrored in the latest legal ruling upholding the Myriad BRCA gene patents (see previous news), when Judge Kimberly Moore said that: “Disturbing the biotechnology industry’s settled expectations now risks impeding, not promoting, innovation”

The question is how to create a regulatory environment that supports innovation in DNA diagnostics whilst maintaining fair access to high quality testing? Identifying ways to manage biomarker IP issues as suggested is no small ask, and would certainly require substantial political will, financial investment and cross-disciplinary collaboration to achieve it. 

The US Federal Court of Appeals has ruled that the company Myriad Genetics is, after all, entitled to US patents held for the BRCA1 and BRCA2 genes (see previous news), mutations in which are associated with hereditary breast-ovarian cancer syndrome.

This epic legal saga has hinged on whether it is possible to patent human DNA sequences; last year, the US government Justice Department said such patents should not be granted because all DNA sequences are a product of nature (see previous news). Conversely, the new ruling from a panel of three judges supports the current policy of the US Patent and Trademark Office by stating that isolated DNA is patentable because it is markedly different from the DNA that exists within the body and is therefore not merely a product of nature, after all.

A third patent claim over the analytic process for examining genes to identify cancer-associated mutations was ruled invalid on the basis that it involved ‘patent-ineligible abstract mental steps’. Myriad was nevertheless buoyant after the decision, but – unsurprisingly - the plaintiffs were said to be considering appealing to the full Court of Appeals or the Supreme Court.

Comment: It is apparently possible to split legal hairs endlessly over whether DNA is or is not patentable, and these patent claims will certainly be fought to the bitter end, as they are a crucial test case for future decisions. However, lawyer Dan Vorhaus also notes that this case does not even begin to address issues such as the impact of whole genome sequencing on patents for isolated DNA sequences. Unfortunately, the snail-like legal process makes it in many ways wholly unsuited to handling the lightning pace of the biomedical sector. 

The Multiple Sclerosis Society together with and the UK Stem Cell Foundation are funding three studies into the use of stem cells to treat multiple sclerosis (MS).

The studies will look at different aspects in the use of stems cells to treat MS. One of the studies is an international trial involving 150-200 people with MS, which will begin later this year. Stems cells from bone marrow of people with MS will be taken, grown and re-injected into the bloodstream. It is hoped these cells will be able to repair damage in the brain. The other studies are laboratory based; one will examine how stem cells can be used to treat optic neuritis (an inflammation of the optic nerve that can cause vision loss) and the other will compare stem cells from people with a progressive form of MS to those without the condition to try and uncover new treatments.

Currently there are no clinically proven stem cells treatments for MS and the availability of such treatments has led to conflict (see previous news). It is hoped that this study will lead to the availability of evidence-based treatments much quicker and give patients access to safe and effective care.

Sir John Bell, the chairman of the government’s advisory Human Genomics Strategy Group (HGSG) has said that the UK is missing out on the opportunities for both patient and commercial benefits offered by modern genomics.

In an interview with Mark Henderson of the Times newspaper, Sir John says that the National Health Service (NHS) is ‘completely unprepared’ to deliver personalised, genome-based medical care.

Prime Minister David Cameron is reportedly enthusiastic about the potential of genomic medicine to improve medical care, but Sir John has warned that the NHS in not ready to adopt the emerging innovations, despite mounting evidence that the improvements in diagnosis and treatment they offer could ultimately save money.

The latest news of genomics as a diagnostic tool to reveal the cause of serious disease in a young girl from the UK (see previous news) was also highlighted as an example of the potential benefits as yet unavailable via the health service.

Sir John identifies policy barriers to the uptake of genomic technologies including failures to plan for the future, a lack of incentives for commercial development, unsuitable evaluation procedures for genetic tests, and a widespread lack of understanding of the uses of genetic testing among health professionals.

Comment: The PHG Foundation’s independent report and policy recommendations on the measures needed to drive prompt adoption of whole genome sequencing technologies into the NHS are to be presented to the HGSG this autumn. The report, which draws on evidence and discussion with top UK experts in genetics and health, will provide a coherent roadmap for the health service to integrate genomics into standard clinical practice across a wide range of medical specialities. 

The first example of whole genome sequencing (WGS) for medical purposes in the UK has been cited as a major research project on the use of WGS in medicine begins.

Genome sequencing was performed on DNA from a four year old girl with a serious skeletal disorder called craniosynostosis and her parents by researchers at Oxford University. They identified a mutation in the gene HUWE1 that is likely to have caused the abnormality and is also associated with learning difficulties; neither parent carried the mutation.

Whilst this finding does not have any immediate implications for the girl’s medical treatment, as has been the case for other recent examples of clinical WGS (see previous news), the family will nevertheless benefit from a clear diagnosis. Besides avoiding the need for further investigations, the findings reveal that the girl’s younger brother and any future siblings are not at increased risk of the same condition, and will also be of value in helping obtain the special educational support she is likely to need.

The Oxford researchers have announced a major collaboration with sequencing company Illumina to produce whole genome sequences for 500 further  individuals with serious diseases ‘that pose major challenges in diagnosis, treatment, and care’, focusing particularly on rare genetic conditions, cancer and immunological disorders.

Professor Peter Donnelly, Director of the Wellcome Trust Centre for Human Genetics at the University of Oxford where much of the sequencing will be performed said the project “represents a crucial step as we move towards a new healthcare paradigm in which genetic information from next-generation sequencing is likely to become much more widely used in routine medical practice", noting also that “To see a real example where sequencing makes a difference to a family was incredibly moving”. 

Up to 90% of US physicians believe they are ill-prepared to meet the challenges of implementing personalised medicine – in spite of widespread agreement that it will ultimately influence the profession and their day to day practice.

The good news is that 9 in 10 physicians are interested in learning more about personalised medicine.   800 US physicians (from oncology, cardiology, and primary care) were surveyed. 8 in 10 recognise that personalised medicine will ultimately influence the medical profession in general. However, only approximately 10% of primary care physicians and cardiologists and 30% of oncologists say they are very familiar with current issues and advances in personalised medicine. Only about half of these doctors are confident in their ability to identify appropriate patients for testing, choose the right test, and understand, interpret, and explain results to their patients.   The report also finds that physicians share consumer concerns about privacy. Up to approximately 90% of physicians say they are concerned about the potential misuse of genetic information.   The survey reflects earlier recommendations from the US Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS) on the genetics education of clinical and public health professionals (see previous news).

The legal challenge to US government funding for human embryonic stem (HES) cell research has been rejected by a judge.

Adult stem cell researchers claimed that such funding diverted National Institutes of Health (NIH) resources away from adult stem cell research and created an incentive for the further destruction of human embryos to meet increasing demands for HES cell lines.

Last year US District Judge Royce Lamberth placed an injunction on federal funding for HES cell research on the grounds that it violated the Dickey-Wicker Amendment, a legal prohibition of federal funding for research that involves the destruction of embryos (see previous news). This was injunction was overturned by the Court of Appeals earlier this year (see previous news).

Now, Judge Lamberth has dismissed the current legal case saying that he is obliged to accept the court’s decision that the Dickey-Wicker Amendment was not applicable for research using HES cell lines provided that the original research that created the cell lines (involving the destruction of human embryos) was not federally funded.

NIH director Francis Collins said that: “This ruling will help ensure this groundbreaking research can continue to move forward”, but the lawyer for the plaintiffs Stephen Aden of the Alliance Defense Fund said: "Americans should not be forced to pay for experiments that destroy human life, have produced no real-world treatments, and violate federal law”, adding that they would consider appealing,

Comment: This decision signals another victory for supporters of HES cell research, but since the law remains open to interpretation, there is scope for another reversal in the event of an appeal. While public opinion remains divided over the ethics of medical research to relieve suffering on the one hand, and the commodification of human embryos on the other, there appears to be no compromise. 

There will be blood

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Optimizing Bob Guthrie's legacy - storage and use of residual newborn screening specimens.

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Storage and use of residual newborn screening blood spots: A public policy emergency.

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Genomics for the world

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Microbial genomics and infectious diseases.

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Give the new generation a chance.

Murenzi R. Nature. 2011 Jun 29;474(7353):543.

Alzheimer’s genetics: finding risk factors.

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Facilitating clinical implementation of pharmacogenomics.

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Genetics and variable drug response.

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Genomic imprinting: the emergence of an epigenetic paradigm.

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The future of model organisms in human disease research.

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Regenerative medicine: drawing breath after spinal injury.

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How to meet the challenges of ageing populations

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Promoting convergence in biomedical science.

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Good vibrations.

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Biomarking the way.

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