News & views
Since the last time we ran this course – we have been tracking the appearance of genomics in the news in order to assess how salient it is in the ever changing news cycle.
It has surprised even us how frequently genomics news stories appear. Almost daily we hear about the impact of genomics on healthcare and how gene-directed diagnosis and therapies are transforming our understanding of widely divergent fields of medicine. We thought we would share with you some of the stories we found particularly interesting. They exemplify the extent to which genomics is going to change everyone’s lives, whether as a patient or as a healthcare professional.
Researchers at the University of Exeter have discovered to their surprise, that a genetic predisposition to eating sweet things appears to be linked with having less body fat. The international study, published recently in the journal Cell Reports, analysed genetic and health information from over 450 000 individuals enrolled in the UK biobank project.
Twenty percent of the European population carry a genetic variant in the FGF21 gene (a key regulator of glucose homeostasis) that is linked to an increased craving for and consumption of sugary food. Researchers found, rather counterintuitively, that people with this variant tend to have less total body fat, however they also tend to have increased blood pressure and waist-hip ratio.
Whilst this finding appears unexpected, this variant is only a small piece of a very complex puzzle connecting genetic variation, diet, metabolism and the risk of obesity and diabetes. FGF21 encodes a hormone which clearly has pleiotropic metabolic effects extending well beyond an influence on sugar consumption. Interest in this variant and others is part of a wider aim to understand these biological pathways, in the hopes of identifying targets to treat obesity and diabetes.
Genome analysis solves Atacama mystery
Over a decade ago, a mysterious skeleton was unearthed in the Atacama region of Chile. Dubbed ‘Ata’, the tiny skeleton appeared human but was only six inches long. Despite being smaller than a newborn baby, the bones were surprisingly mature, and there were several other unusual features, including a cone-shaped cranium and only 10 ribs, rather than the usual 12.
The find was widely reported in the press, with speculation as to Ata’s origin ranging from that of a non-human primate, to something extra-terrestrial. A team of researchers analysing the find established through initial DNA studies that the body was human in origin, and then undertook whole genome sequencing of the skeleton to establish the cause of the unusual phenotype.
Their findings, published recently in the journal Genome Research, and reported by the BBC, show that Ata is a human female, carrying mutations in an array of genes linked to diseases of short stature, cranial malformations, rib anomalies, skeletal dysplasia and premature joint fusion. Despite the pathologically advanced bone maturity, it is thought that Ata was in fact stillborn, or died shortly after birth and that the skeleton itself may be no more than 40 years old.
Human gene editing in vivo – a new frontier
Gene editing using the Cas-CRISPR ‘molecular scissors’ has transformed the ability to correct mutations in DNA, and caused much excitement amongst gene therapy researchers.
Trials of using gene editing for gene therapy, attempting to correct mutations causing human diseases, have begun for a variety of conditions. However, until recently this has only been attempted outside of the human body, by removing cells, editing them and returning them to the patient. This works well for diseases of the blood and bone marrow, but cannot be so easily done for diseases affecting solid organs.
Now, the first clinical trials of using gene editing inside the patient’s body have begun. As reported in the BBC, in November Sangamo Therapeutics announced the landmark first treatment using in vivo gene editing of a patient with Hunter syndrome (mucopolysaccharidosis type II), a rare genetic condition affecting the liver’s ability to break down mucopolysaccharides, leading to damage to the brain and other organs.
The experimental therapy is infused into the bloodstream, then travels to the liver where the ‘molecular scissors’ (called zinc finger nucleases) are activated, to precisely remove the stretch of DNA containing the disease-causing mutation and replace it with the correct DNA code.
At the moment clinical trials are in the early stages and the focus is very much on whether this technology is safe. If it should prove to be not only safe but effective, it could be a great leap forward for gene therapy research. Sangamo are undertaking two additional clinical trials using in vivo gene editing, for MPS I (Hurler syndrome) and for haemophilia B. Results are awaited with interest.
For those wishing to find out more about this and other strategies to translate genome editing technology to the clinic, see this Nature Medicine review.
Are investors too cynical for a cure?
The potential for gene therapy to transform people’s long term health outcomes hit the headlines again recently, for the wrong reasons…
An article from Science news website, iflscience, highlighted the issue that financiers may be put off investing in potentially curative therapies, because there is a lot less money in curative treatments than those for the long-term management of disease.
They quote a report leaked from a Goldman Sachs analyst to his clients, stating that: “The potential to deliver ‘one-shot cures’ is one of the most attractive aspects of gene therapy, genetically-engineered cell therapy and gene editing. However, such treatments offer a very different outlook with regard to recurring revenue versus chronic therapies.”
In his report, the analyst cites the example of the ground-breaking hepatitis C treatment, sofosbuvir, from Gilead Sciences. A twelve-week course of treatment with this anti-viral drug is able to completely clear the virus in most patients, and thus also helps to prevent its spread. In 2015, revenue from this treatment was $12.5 billion; this year it has fallen to less than $4 billion.
So it seems that what is better for patients is worse for profits. The article concludes that In the case of rare diseases where the profit margins are lower, this could well put the private-sector funding of potential cures at risk, and that the development of these treatments may increasingly rely on philanthropic or government funding.
Which of these stories interests you most and why? Have any other stories about genomics in the press caught your eye?
© St George’s, University of London