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.

  • Embryonic genome editing – a further sting in the tail?

Many will have followed the story of the rogue Chinese scientist, He Jiankui, who was roundly condemned by the international scientific community when, in November 2018, he announced the birth of twin baby girls born after embryonic genome editing to prevent HIV infection. Now, in a further twist, scientists have discovered that the genetic change introduced by He, far from being beneficial to the twins, could, in fact, shorten their lives.

He used CRISPR-Cas9 genome editing to target a gene called CCR5, that encodes an immune cell surface protein which HIV latches onto to infect cells. 10% of northern Europeans carry a naturally-occurring mutation in CCR5 which confers protection against HIV. He attempted to mimic this effect, and introduced mutations that disabled a single copy of CCR5 in one of the twins, and both copies of the gene in the other.

In a recent study published in Nature Medicine, researchers from the University of California have analysed the clinical and genomic data of over 400,000 UK Biobank participants and found that the death rate was on average 21% higher in 41- to 78-year-olds carrying mutations in both copies of CCR5 than in those with mutations in only one or neither copy. The authors hypothesise, “In this case, the cost of resistance to HIV may be increased susceptibility to other, and perhaps more common, diseases.”

He’s embryonic genome editing has already been universally condemned as unsafe and unethical, and this latest twist only serves to underline further the dangers of the premature and unregulated use of this powerful technology.

  • Could a one-off injection prevent heart attacks?

Imagine if you could drastically reduce your risk of having a heart attack, the world’s leading cause of death, with just a single injection. Well, a team of researchers in the US have announced plans for a new gene therapy that aims to do just that.

An individual’s risk of heart attack is affected by their level of low-density lipoprotein (LDL) cholesterol. People with the genetic condition familial hypercholesterolaemia have high levels of LDL cholesterol and have a dramatically increased risk of a heart attack. Whilst taking statins can reduce LDL cholesterol, these need to be taken daily for life, whereas this new therapy aims to reduce LDL cholesterol permanently with a one-off injection, by modifying the genes that produce it.

Healthy individuals have been identified who have naturally-occurring mutations in a gene called PCSK9 that is involved in making LDL cholesterol. These people have only one working copy of PCSK9, have low levels of LDL cholesterol and appear remarkably resistant to heart attacks. The gene therapy under development will use the CRISPR-Cas9 gene-editing tool to target and disable one copy of the PCSK9 gene, thereby artificially recreating this effect.

This therapy is being developed by a US biotech company called Verve Therapeutics who report successful trials to date in mice, in whom cholesterol was successfully reduced by 35-40%. If follow-up trials in monkeys prove successful they will launch a trial in patients with homozygous familial hypercholesterolaemia, whose cholesterol levels are extremely high and who are at high risk of early heart attack.

Dr Kathiresan, the cardiologist and geneticist from Harvard Medical School who is leading the project claims that, ultimately “The therapy will be relevant, we think, to any adult at risk of a heart attack”. Whilst this is in many ways an enticing prospect, it is early days in its development and its safety profile would need to be firmly established before that potential could become a reality.

  • Gene therapy for Spinal Muscular Atrophy – what price a life?

Pharmaceutical company Novartis has confirmed that it has received US FDA approval for its spinal muscular atrophy (SMA) gene therapy, Zolgensma, priced at a staggering US$2.125 million for a one-off dose, making it the world’s most expensive drug.

Spinal muscular atrophy type 1 (SMA1) is the most common fatal genetic disease in infants. Affected infants commonly die before the age of two years. The condition is caused by mutations or deletions of the SMN1 gene, which produces a protein necessary for the survival of motor neurons. Affected individuals inherit two faulty copies of SMN1 and are thus are unable to produce SMN protein.

Zolgensma works by using a viral vector to deliver a working copy of the SMN1 gene to the target motor neurons. Novartis has defended the high price with the rationale that a one-time treatment is more valuable than repeated treatments. They have so far successfully treated over 150 patients with Zolgensma, although their data at present only extends to about 5 years, with follow-up studies ongoing.

Zolegensma will be competing with the existing therapy, Biogen’s Spinraza. This antisense oligonucleotide treatment increases SMN protein production but requires repeated infusions every 4 months, also at considerable cost. NHS England has recently reached an agreement with Biogen under which it will fund treatment for a limited time whilst collecting data on effectiveness.

Whilst it is undoubtedly wonderful news that effective treatments are now available for this previously fatal condition, it is also deeply upsetting that the price will put them out of reach for many individuals worldwide. On the other hand, pharmaceutical companies need to fund ongoing drug development and only a fraction of treatments developed will ever achieve commercial success.

So is the price justified or do you feel the price of a life is too high in this case? Where do you stand?

Talking point

Which of these stories interests you most and why? Have any other stories about genomics in the press caught your eye?

Share this article:

This article is from the free online course:

The Genomics Era: the Future of Genetics in Medicine

St George's, University of London

Get a taste of this course

Find out what this course is like by previewing some of the course steps before you join: