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Issue 936 (05 February 2018)

 

Welcome to BioNews by email, published by the Progress Educational Trust, providing you with news, comment and reviews on genetics, assisted conception, embryo/stem cell research and related areas.

Visit the BioNews website at www.bionews.org.uk where you can subscribe for free to receive BioNews by email in one of three formats, and search the archive of more than 6,000 articles.

 

 

CONTENTS

Comment

News Digest

Reviews

 


 

Beyond the Mediterranean diet: Improving IVF success in women with higher BMI

05 February 2018

By Dr Thanos Papathanasiou

Bourn Hall Clinic Regional Lead Clinician, Cambridgeshire and Norfolk, UK

Appeared in BioNews 936

Being a healthy weight, eating a varied diet with plenty of fruit and vegetables, taking regular exercise and cutting down on alcohol – this is all good advice for everyone. But the direct influence on these factors on the fertility of both men and women, highlighted this week by a study suggesting a 'Mediterranean diet' in women can boost IVF success rates (see BioNews 936) is now becoming better understood.

One example where weight impacts fertility is Polycystic Ovary Syndrome (PCOS), which affects 5-10 percent of women. PCOS is a complex syndrome that produces a wide variety of symptoms, such as acne, hirsutism, menstrual irregularities, obesity and glucose intolerance, that are present in some women and not in others. This makes it difficult to both diagnose and treat.

I often find that women with PCOS have had their symptoms treated by different specialists over a number of years. For example, acne is treated with antibiotics and menstrual disturbances with the contraceptive pill.  

As the pill often masks the symptoms, it is only when they have failed to conceive that the PCOS has been correctly diagnosed. Sadly, by this time many have an increased BMI (body mass index), which often makes fertility treatment less effective and pregnancy more of a problem.

What is now emerging is that PCOS is associated with a metabolic disturbance, which is characterised by insulin resistance and high levels of insulin in the blood. In some women, raised insulin levels impacts the ovaries, preventing them from releasing mature eggs, and so leading to infertility.

PCOS can be diagnosed with blood tests for serum testosterone, LH (luteinising hormone) and FSH (follicle stimulating hormone) supported by ultrasound, which reveals the immature follicles on the surface of the ovary.

The metabolic imbalance can also make it difficult to lose weight and it is not unusual for women with PCOS to report a history of weight problems, obesity, rapid weight gain, and if this is left unchecked it can increase the risk of pre-eclampsia, gestational diabetes, high blood pressure and miscarriage. It can also raise the risk later in life of developing diabetes and heart disease.

These long-term health implications make accurate diagnosis and early treatment even more important; not just for fertility but for the health of the woman during pregnancy and beyond. The encouraging news is that early detection and lifestyle management can greatly improve their overall health and boost their natural fertility.

With the right support women can lose weight ahead of fertility treatment and evidence from our clinic and the literature suggests that this is very effective. One study found that in obese women where ovulation has ceased, a 5-10 percent weight loss restored ovulation to over half the women within six months.  

If lifestyle management alone is not sufficient to restore ovulation then stimulation with anti-oestrogens such as clomiphene citrate remains the treatment of first choice. But this needs to be carefully monitored, preferably with ultrasound.

Where IVF is required the NICE guidelines state that women should have a BMI of 19-30, and ideally below 25, to be eligible for IVF treatment. This is because women with a BMI of between 25 and 30 have lower success rates when all other factors are equivalent.

Little is known about the effect of ovarian stimulation drugs on this group of women, as most trials focus on women with a BMI of 19-25, and those with a higher body weight are typically excluded. Ovarian stimulation is used to increase the number of recruited eggs for IVF.

The types of drugs and their timing are defined by protocols. There are two main protocols, LDP (Long Downregulation Protocol) where down-regulation is used to control the woman's natural cycle, followed by ovarian stimulation to increase egg production. The other is Antagonist Protocol, which uses ovarian stimulation without prior down-regulation. Instead, an antagonist drug is introduced during the course of stimulation to prevent ovulation and, therefore, allow the retrieval of eggs for IVF.

We are fortunate at Bourn Hall, founded by pioneers Dr Patrick Steptoe and Professor Robert Edwards, that as the world's first IVF clinic we have data going back nearly 40 years. We used this historical data to compare success rates for two widely used IVF protocols, LDP and Antagonist Protocol and the results were very interesting.

The study compared the outcomes of women with an average BMI of 22 with those of 27 for each protocol. All other factors, including age, cause of subfertility, previous IVF treatment, starting stimulation dose, use of ICSI technique and number of embryos transferred, were accounted for.

Women treated with the LDP protocol showed a significant difference in pregnancy rates. The lower-weight group had an average 45 percent pregnancy rate compared to 31 percent for those with a higher BMI. However, the success rates for the two groups treated with the Antagonist protocol were similar: 41 percent for those of the lower weight compared to 39 percent for the higher weight group.

Both protocols are widely used during IVF. The LDP protocol has been historically the 'gold standard' protocol in IVF.  Bourn Hall Clinic was instrumental in the development of this protocol during the early years of IVF. However, when these early protocols were developed, only a small minority of the population had a BMI of over 25 (defined by the BMI healthy weight calculator as 'overweight'). Now many more women are in this category and this could impact on the effectiveness of the drug protocols.

The study also suggests that the lower success rates achieved for these women during IVF may not be just as a result of the 'obesity factor', but instead that outcomes for this group can be improved through the improved selection of stimulation protocol.

This study provides new information suggesting that protocol selection should be weight-adjusted, as this will likely maximise IVF success for this group of women.

A balanced and healthy diet with less refined carbohydrates and fats and less alcohol consumption can benefit both men and women and help tip the balance where subfertility of both partners is affecting conception. However, for those who are struggling to lose weight these findings give encouragement and also provide health professionals with some new insights into fertility care.

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

12 February 2018 - by Elizabeth Oliver 
Researchers have grown fully developed human eggs in the laboratory for the first time...
12 February 2018 - by Dr Anna Smajdor 
Academics have written at length on the ethics of reproductive technologies, abortion and speculative possibilities such as reproductive cloning. But pregnancy itself up until recently has been a somewhat neglected topic...

05 February 2018 - by Isobel Steer 
Researchers in Greece have found that a Mediterranean diet is linked with an over 65 percent improvement in a woman’s chances of a successful IVF pregnancy...
08 December 2014 - by Dr Nicoletta Charolidi 
Women who consume a Mediterranean-style diet are less likely to show evidence of 'cellular ageing' and therefore more likely to live longer, say US researchers...
19 August 2013 - by Dr Lux Fatimathas 
Claims for the health benefits of the typically Mediterranean diet high in olive oil, fish, and complex carbohydrates are common, if hard to substantiate...


 

UK experts call to action on IVF funding and multiple births

05 February 2018

By Dr Kimberley Bryon-Dodd

Appeared in BioNews 936

A report by the UK's Royal College of Obstetricians and Gynaecologists (RCOG) suggests that increasing government funding of IVF could decrease the number of multiple pregnancies and their associated strain on the NHS.

The scientific impact paper states that around one in five (19.8 per cent) of IVF  (in vitro fertilisation) deliveries in the UK in 2011 were multiple births.  Multiple embryos are sometimes transferred during an IVF cycle in an effort to reduce costs for patients funding their own treatment.

While the National Institute for Health and Care Excellence (NICE) currently recommends three fully funded cycles for IVF for all patients who meet set criteria, the number of cycles offered differs depending on where in the country patients live. In some regions, only one or no funded cycles are offered. Up to six in ten IVF cycles are being funded by patients themselves according to the RCOG study.

Professor Lesley Regan, president of RCOG, said: 'IVF is a cost-effective treatment and should be available on the NHS. Yet current access to treatment is a postcode lottery which is completely unacceptable for couples with infertility problems.

'Government funding for three full IVF cycles, as recommended by NICE guidelines, would provide a greater incentive for IVF centres and their patients to adopt single embryo transfer more regularly.'

Mr Tarek El-Toukhy, a consultant gynaecologist and specialist at Guy's and St Thomas's Hospital in London, and lead author of RCOG's report, said: 'The health and financial burden it places on women, families and the NHS cannot be overstated. To ensure rates of multiple births remain low, there is little doubt that the single most important factor that could enhance the acceptance of single embryo transfer among patients and practitioners is appropriate funding for IVF treatment.'

Multiple pregnancies pose risks to both the babies and mother with the chances of a premature labour six times more likely than a singleton pregnancy. Mothers of multiples have a higher risk of pregnancy-induced high blood pressure, gestational diabetes, haemorrhage following birth, and postpartum depression as well as heightened symptoms of anxiety and parenting stress.

Aileen Feeney, chief executive of Fertility Network UK, told The Guardian: 'For couples experiencing years of heartbreak in their struggle to have children, the decision to choose a single embryo transfer rather than a multiple embryo transfer can be a very tough one which is made even more difficult if they are facing the financially crippling costs of private IVF treatment.'

Efforts have been made to cut the number of multiple births in the UK, including promoting the benefits of single embryo transfer. The HFEA (Human Fertilisation and Embryology Authority) has found a reduction in the national multiple birth rate from 24 percent in 2009 to 11 percent today.

SOURCES & REFERENCES
The Guardian | 02 February 2018
 
Royal College of Obstetricians & Gynaecologists | 02 February 2018
 
BBC | 02 February 2018
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

18 December 2017 - by Ewa Zotow 
The first ever report on the state of the fertility sector has been released by the Human Fertilisation and Embryology Authority (HFEA). It highlights marked improvements in several aspects of performance, including the reduction in multiple births rates, and addresses shortcomings in the sector...
06 November 2017 - by Sarah Norcross 
Sarah Norcross, Director of the Progress Educational Trust and Co-Chair of the campaigning organisation Fertility Fairness, speaks on TV and radio about worsening access to publicly funded IVF...
30 October 2017 - by Shaoni Bhattacharya 
Access to IVF in England has worsened considerably over the last five years, according to data obtained by Fertility Fairness...
14 August 2017 - by Dr Kimberley Bryon-Dodd 
Funding cuts by the UK's National Health Service has meant that 13 areas in England have restricted or halted IVF treatment since the start of 2017, according to Fertility Network UK...
23 January 2017 - by Dr Rachel Brown 
Steve McCabe MP has led a parliamentary debate on the variable provision of fertility treatments across the UK, calling for a revision to how fertility services are funded and provided...


 

Record-breaking study links over 950 genes to insomnia

05 February 2018

By Shaoni Bhattacharya

Appeared in BioNews 936

A large study of the genomes of over 1.3 million people has found 956 genes implicated in insomnia.

The genome-wide association study (GWAS) examined the genomes of people from the UK's Biobank, and those from the personal genomics company 23andMe Inc, based in Mountain View, California. With 1,331,010 participants, the study authors believe this is the largest GWAS to date.

Despite being a common complaint (one-third of the general population report insomnia) only a handful of genes had previously been associated with the disorder (see BioNews 905).

An international team of scientists, lead by researchers at the VU University in Amsterdam, The Netherlands, surveyed participants on their self-reported insomnia symptoms while conducting various genome analyses.

Their findings – yet to be peer-reviewed – were published on the bioRxiv pre-print server.

'Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment,' write the authors.

In particular, many of the genes that were associated with insomnia were expressed in a type of brain cell known as a medium spiny neuron; these form 95 percent of the brain's striatum. This area is involved in voluntary movement.

The researchers also found some genetic overlap between insomnia and certain neuropsychiatric traits like anxiety and depression.

Dr Stuart Ritchie, a psychologist at the University of Edinburgh, UK, tweeted that the study was 'amazingly massive'.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

22 January 2018 - by Sam Sherratt 
Over the last few years we've seen a welcome explosion in the number of scientific podcasts aiming to spread the gospel about new research that may otherwise miss the attention of the mainstream media. With this in mind, I recently sat down to listen to an episode of Naked Genetics, a weekly podcast covering the 'latest genetics news and breakthroughs from the DNA world'...
15 January 2018 - by Eleanor Taylor 
The ever-expanding limits of human reproduction are creating complex ethical and political challenges. One topic that has generated much contention is the possibility of editing the genome of human embryos...
06 November 2017 - by Julianna Photopoulos 
Scientists have found 27 new tumour suppressor genes...
19 June 2017 - by Lea Goetz 
Researchers have found seven risk genes for insomnia through two large genome-wide and gene-based association studies...
08 February 2016 - by Dr Barbara Kramarz 
Scientists have used data from personal genomics company 23andMe to identify a set of genes that are linked to being a 'morning person'...


 

Ibuprofen in early pregnancy may harm the future fertility of baby girls

05 February 2018

By Georgia Everett

Appeared in BioNews 936

Women taking over-the-counter ibuprofen during early pregnancy could potentially be damaging their unborn baby girl's future fertility irreversibly, according to a new study.

The research published in Human Reproduction suggests that taking the common painkiller for only two days within the first 24 weeks of pregnancy could deplete the unborn daughter's ovarian germ cells, causing a reduced fertile period and possibly infertility later in life. These cells would later differentiate into cells that make the follicles where the eggs are developed and released. 

Dr Séverine Mazaud-Guittot of the University of Rennes, the lead author of the study, said: 'Baby girls are born with a finite number of follicles in their ovaries and this defines their future reproductive capacity as adults. […] A poorly stocked initial reserve will result in a shortened reproductive life span, early menopause or infertility - all events that occur decades later in life.'

Two to seven days' exposure to ibuprofen dramatically reduced the germ cell stockpile in human fetal ovaries. After this exposure, the ovaries did not recover fully from the damage, the scientists found.

'This suggests that prolonged exposure to ibuprofen during fetal life may lead to long-term effects on women's fertility and raises concern about ibuprofen consumption by women during the first 24 weeks of pregnancy,' Dr Mazaud-Guittot said. 

The study used tissue samples from 185 aborted 7 to 12-week-old human fetuses, and cultured the tissue in the laboratory. Half of the group were exposed to ibuprofen and half of the group were not, as a control. The researchers found that tissue exposed to realistic concentrations of ibuprofen, comparable to those if a mother had taken the painkiller, had approximately half the number of ovarian germ cells. 

'We found there were fewer cells growing and dividing, more cells dying and a dramatic loss of germ cell numbers, regardless of the gestational age of the fetus,' said Dr Mazaud-Guittot. 'We saw cell death as early as after two days of treatment.'

It is currently estimated that 30 percent of pregnant women take ibuprofen within the critical 24-week fetal development period. Fortunately, the advice on ibuprofen consumption during pregnancy does not need to change much in light of this study. The NHS currently advises expectant mothers to not take the drug before 30 weeks gestation. Earlier studies have associated the painkiller with an increased risk of fetal malformation and miscarriage.

Prof Ying Cheong, reproductive medicine researcher at the University of Southampton, who was not involved in the study, praised the study. 'The work is of excellent quality and represents important scientific advancement. We now need longitudinal epidemiological data to further confirm these observations as to whether exposure in early pregnancy relates to reduced fertility,' he said. 'Generally speaking, ibuprofen should be used in pregnancy sparingly but the current evidence should not be used to "scare-monger" women into not using these rather effective simple analgesics at all.'

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

15 January 2018 - by Nina Chohan 
Men who regularly take the maximum recommended dose of ibuprofen may be at an increased risk of fertility issues...
01 February 2016 - by Fiona Ibanichuka 
Scientists have discovered that the use of painkillers during pregnancy in rats may reduce the fertility of their offspring...
15 November 2010 - by Seil Collins 
New preliminary research suggests a possible link between the use of mild painkillers during pregnancy and the birth of male children with congenital cryptorchidism, more commonly known as undescended testes, a condition which reduces male fertility. The rates of undescended testes seen in the study remained relatively low....


 

Women selected for mitochondrial donation in UK

05 February 2018

By Sam Sherratt

Appeared in BioNews 936

The Human Fertilisation and Embryology Authority (HFEA) has granted permission for doctors to create the UK's first 'three-person' children by mitochondrial donation.

Doctors at Newcastle Fertility Centre successfully applied to treat two women and are now allowed to create embryos by combining fertilised eggs created through IVF with mitochondria from a female donor. The resulting embryos will be implanted in the two women.

Mitochondrial donation was developed for use where women carry disease-causing genetic mutations in their mitochondria. Mitochondria are small structures located in the cell which produce energy and also house their own distinct DNA, separate from the main bulk of DNA located in the cell nucleus.

To avoid passing on these mutations to their children, the healthy nuclear DNA of the intended parents is removed from a fertilised egg and transplanted into the fertilised egg of a female donor whose nuclear material has been removed, resulting in an embryo with nuclear DNA from two parents and the mitochondrial DNA of the donor. An alternative method involves performing the DNA transfer before fertilisation.

The decision by the HFEA has already been warmly welcomed by UK advocacy groups. Liz Curtis, founder of the British mitochondrial disease charity The Lily Foundation, said: 'The first patient licence for mitochondrial donation has been a long time coming, but now at last women with mitochondrial disease have a chance to have children without fear of passing on this devastating condition.'

In both of the currently approved cases, the women carry a genetic mutation for a condition called MERRF syndrome. The disease is characterised by twitching, weakness and progressive tightness in the muscle fibres. This can lead to symptoms such as difficulty coordinating movement, seizures and heart disease.

Professor Salvatore DiMauro, an expert in mitochondrial disease at Columbia University in New York, said: 'It's good to do this. MERRF (myoclonic epilepsy with ragged-red fibers) is a crippling disease. It's the only way to be sure it is not passed on.'

Newcastle Fertility Centre, which has pioneered much of the research in this field, received a licence to perform mitochondrial donation techniques last March from the HFEA (see BioNews 893), but it has taken nearly a year for these two specific cases to be approved. 

Responding to the news, Sarah Norcross, Director of the Progress Educational Trust, said: 'The pace at which these treatments are being rolled out may seem slow, but this highly regulated and measured approach will ensure the highest standards of treatment and follow-up research. Options which for many years have been tantalisingly out of reach to patients are now a step closer.'

SOURCES & REFERENCES
BBC | 02 February 2018
 
The Guardian | 01 February 2018
 
New Scientist | 02 February 2018
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

12 February 2018 - by Elizabeth Oliver 
Researchers have grown fully developed human eggs in the laboratory for the first time...

19 June 2017 - by Shaoni Bhattacharya 
The fertility doctor who led the team which produced the world's first baby through mitochondrial replacement therapy is now looking to use the same technique in a commercial venture...
03 April 2017 - by Helen Robertson 
Details of the world's first successful use of mitochondrial replacement therapy in IVF have been published...
20 March 2017 - by Georgia Everett 
Doctors at Newcastle Fertility Centre have been granted the first UK licence to use mitochondrial replacement therapy as a fertility treatment to prevent the inheritance of mitochondrial disease...
19 December 2016 - by Annabel Slater 
The UK has become first country in the world to formally approve the creation of IVF embryos through mitochondrial donation...
05 December 2016 - by Dr Julia Hill 
Scientists advising the HFEA have recommended that the technique of mitochondrial replacement therapy be approved for clinical use in the UK...


 

Mediterranean diet in women improves IVF success

05 February 2018

By Isobel Steer

Appeared in BioNews 936

Researchers in Greece have found that a Mediterranean diet is linked with an over 65 percent improvement in a woman’s chances of a successful pregnancy with IVF

Inhabitants of the Mediterranean regions typically enjoy a diet rich in fresh fruit, vegetables, whole grains, fish and olive oil. Their diet is balanced and lower in the 'meats and mayonnaise' consumed typically in the UK and USA. But researchers at the Department of Nutrition and Dietetics at Harokopio University of Athens wanted to find out whether this diet also affected IVF outcomes.

The team, led by Dr Nikos Yiannakouris, looked at a sample group of 244 women aged 22 to 41 who enrolled at an assisted conception unit in Athens. They aimed to study the effects of diet 'beyond body weight' and therefore only studied non-obese women. The study also controlled for various other factors, including physical activity, anxiety and supplement use. 

The team used a food-frequency questionnaire to give each woman a Mediterranean diet score, and divided up women with high, medium or low scores. The highest scoring group of 86 women had the greatest adherence to a Mediterranean diet. These women also had a 65 to 68 percent greater likelihood of achieving a successful pregnancy and live birth compared to the 79 women in the lowest scoring group.

'The important message from our study is that women attempting fertility should be encouraged to eat a healthy diet, such as the Mediterranean diet, because greater adherence to this healthy dietary pattern may help increase the chances of successful pregnancy and delivering a live baby,' said Dr Yiannakouris.

For conception, a healthy diet for male partners was just as important as for women (see BioNews 777). 'Previous work from our research group among the male partners of our study has suggested that adherence to the Mediterranean diet may also help improve semen quality.' 

The findings of the study, published in Human Reproduction, cannot be generalised to all women, to obese women, or to women over the age of 35, the authors caution. There was no link between the Mediterranean diet and pregnancy outcomes among women in the older age group. The dominant effect of age on fertility could mask any environmental effects, the authors note. 

The study did not pinpoint any causal mechanism for how the Mediterranean diet could be affecting IVF success. Calling for more research into this question, the group ultimately hopes to develop nutritional guidelines for women to further improve fertility treatment success rates. 

'As more couples worldwide face infertility problems and seek access to assisted reproduction technologies to conceive, it is essential for them to receive counselling on the importance of dietary influences and of adopting a healthy lifestyle,' concluded Dr Yiannakouris. 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

05 February 2018 - by Dr Thanos Papathanasiou 
Being a healthy weight, eating a varied diet with plenty of fruit and vegetables, taking regular exercise and cutting alcohol – is all good advice for everyone. But the direct influence on these factors on the fertility of both men and women, highlighted this week by a study suggesting a 'Mediterranean diet' in women can boost IVF success rates is now becoming better understood...

06 November 2017 - by Professor Joyce Harper 
The American Society for Reproductive Medicine conference was held last week in San Antonio, USA. Several oral presentations of abstracts made it into the popular press and have added to the confusion and inaccurate information fed to the public...
24 October 2016 - by Annabel Slater 
Artificial sweeteners found in soft drinks may reduce female fertility, a study suggests...
08 December 2014 - by Dr Nicoletta Charolidi 
Women who consume a Mediterranean-style diet are less likely to show evidence of 'cellular ageing' and therefore more likely to live longer, say US researchers...
27 October 2014 - by Isobel Steer 
To improve chances of conception, men should drink a pint of beer daily, cut down on coffee, eat more fruit and vegetables (beware a coating of sperm-harming pesticides), and avoid vegetarian or vegan diets...
19 August 2013 - by Dr Lux Fatimathas 
Claims for the health benefits of the typically Mediterranean diet high in olive oil, fish, and complex carbohydrates are common, if hard to substantiate...


 

Vaping linked to impaired DNA repair in mice

05 February 2018

By Theofanis Michailidis

Appeared in BioNews 936

E-cigarette smoke has been found to damage DNA in the heart, lungs and bladder in mice, according to research from New York University's School of Medicine. 

The study investigated whether e-cigarette smoke damages the organs of a mouse and whether it affects DNA repair activity. The researchers exposed mice to e-cigarette smoke for three hours a day, five days a week for three months.

The nicotine in the e-cigarette vapour affected both the mice’s DNA and human cells in a dish, as the vapour made the cells less able to repair the DNA damage. 'It is therefore possible that e-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans,' the researchers wrote in the study, published in PNAS.

The study suggests that the nicotine used in e-cigarette vapour is not risk-free. However experimentation results on animals do not necessarily translate into the same risks for humans, the researchers note. To address this, research on human participants would be necessary. 

'Studies like this are important for building up the evidence around vaping, and how e-cigarette vapour might damage cells in controlled conditions,' said Michael Walsh of Cancer Research UK.

However, it is premature to conclude that vaping causes cancer in humans. The study also did not compare e-cigarette vapour to smoke from traditional cigarettes. Many studies have shown that vaping is less harmful overall to human health than smoking tobacco. 

Jasmine Just of Cancer Research UK told the Guardian: 'Research like this is important, but this lab study only looked at the effects of e-cigarette smoke on cells and on mice, which means it’s not possible to draw any conclusions from this about how e-cigarettes might affect people in real life.' 

Cancer Research UK and other researchers not involved in the study have cautioned that exaggerating the findings of the study could have negative consequences. As many vapers are ex-smokers using e-cigarettes to quit smoking, it should be noted that people with nicotine addictions are still better off vaping than smoking, said Professor Peter Hajek, director of the Tobacco Dependence Research Unit at Queen Mary University of London. 

Claims that vaping causes cancer, as some news sources have reported, are part of 'a long line of false alarms which may be putting people off the switch from smoking to vaping which would undoubtedly be of great benefit to them', Professor Hajek said. 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

08 January 2018 - by Charlott Repschlager 
Drinking alcohol damages blood stem cells by altering their DNA, raising the risk of developing cancer, scientists have found.
18 September 2017 - by Dr Molly Godfrey 
Organoids and CRISPR/Cas9 have been combined in a novel method to study genetic mutations occurring in cancer...
03 July 2017 - by Jennifer Willows 
DNA repair may be reduced in people working at night time, compared with those having a night's sleep, according to new research from the US...


 

Muscle memory exists on the DNA level through epigenetic tagging

05 February 2018

By Dr Loredana Guglielmi

Appeared in BioNews 936

A study led by UK researchers has shown for the first time that human muscles possess a 'memory' of earlier growth, or hypertrophy.

Muscle cells are able to 'remember' which genes are activated or inactivated during physical exercise and use this information to grow larger later in life. This finding could have important implications for athletes training and recovering from exercise-related injuries, or those cheating with performance-enhancing muscle-building drugs.

In the study, published in Scientific Reports, eight healthy males completed a programme of 21 weeks alternating acute and resistance training with a period of no exercise. The investigators performed a biopsy pre- and post-exercise and isolated the genetic material from the muscle fibres. They used a genome-wide approach to screen over 850,000 regions of the human DNA that carry special chemical tags known as epigenetic modifications. Usually, a gene marked with such an epigenetic tag is not expressed.

'In this study, we've demonstrated the genes in muscle become more untagged with this epigenetic information when it grows following exercise in earlier life. Importantly, these genes remain untagged even when we lose muscle again, but this untagging helps "switch" the gene on to a greater extent and is associated with greater muscle growth in response to exercise in later life - demonstrating an epigenetic memory of earlier life muscle growth!' said Dr Adam Sharples, a senior study author at Keele University in Stoke-on-Trent.

The group of DNA regions untagged during the entire training plan contains genes belonging to a cellular signalling system - PI3K/AKT pathway – critical for cell proliferation and protein synthesis. The scientists hypothesised that the enhanced epigenetic untagging of these genes would lead to increased muscle protein levels and hypertrophy.

Robert Seaborne, study co-author and PhD student at Keele University, hopes that the identification of the epigenetic memory involved in muscle bulk increase could help define more appropriate sporting regulations. 'If an elite athlete takes performance-enhancing drugs to put on muscle bulk, their muscle may retain a memory of this prior muscle growth. If the athlete is caught and given a ban - it may be the case that short bans are not adequate, as they may continue to be at an advantage over their competitors because they have taken drugs earlier in life, despite not taking drugs anymore,' he said. 'More research using drugs to build muscle, rather than exercise used in the present study, is required to confirm this.'

SOURCES & REFERENCES
Scientific Reports | 16 January 2018
 
Keele University | 30 January 2018
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

29 January 2018 - by Professor Marcus Pembrey 
The recent demonstration that friends share more of their genetic makeup in common than two people picked at random from their population has been making the headlines...
04 December 2017 - by Dr Kristien Hens and Dr Leni Van Goidsenhoven 
Popular scientific publications regularly have articles with headlines suggesting that 'autism is hereditary' or that the 'risk for developing autism' is mostly caused by genetics...


 

High-dose gene therapy appears toxic in monkeys and piglets

05 February 2018

By Ewa Zotow

Appeared in BioNews 936

Animals given high doses of gene-carrying viruses in a new gene-therapy trial showed signs of severe toxicity.

The viral vector –called AAV9 – was previously successfully used in babies with a severe form of spinal muscular atrophy. Viruses are used in gene therapy because they are able to enter human (and animal) cells and insert a piece of DNA into the patient's chromosome. AAV9 has been widely used and was considered harmless.

The researchers injected young monkeys and piglets with high doses of AAV9 which carried therapeutic genes into the cells of the spinal cord. The animals developed severe damage to the liver and motor neurons within few days post-treatment, and some had to be euthanised.

The author of the study, Dr James Wilson, said: 'What is remarkable is we have not seen it before…If you push the dose of anything high enough, you are going to see toxicity.'

Dr Terence Flotte, a pioneer in human gene therapy and editor of the journal which published the findings, cautioned that these results may not apply to humans. It was not established if the specific virus variant, the human DNA it was carrying or contamination was responsible for the toxicity.

The stock prices of several gene therapy companies have fallen after the publication. However, Dr Flotte warns against 'overreaction' of the research community and suggests that the clinical trials should not halt. The gene therapy may have high therapeutic potential.

'The one and only guiding principle in critical moments like this should be the welfare of patients with the diseases being treated with these therapies,' said the journal's editors, who advocate for full transparency regarding all relevant data and for reproduction of these findings by different labs.

In previous trials, the use of one-dose gene therapy to treat babies born with spinal muscular atrophy led to remarkable success. Most babies showed substantial improvement in motor function and survival. Children with this disorder usually die before the age of two, which has to be taken into account by clinicians weighing the risks and benefits of potential therapies.

The current study highlights the need for careful monitoring of side effects and further research.

'Let's study this, let's not ignore it,' counsels Dr Flotte. 'If the gene therapy research community makes patient welfare as the sole priority, it will ultimately be beneficial to us all.'

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

08 January 2018 - by Isobel Steer 
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30 August 2011 - by Rosemary Paxman 
Over a dozen children with 'boy in bubble' syndrome are alive and well, with functioning immune systems, nine years after undergoing gene therapy to correct their disorder, researchers report....
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A boy enrolled on a pioneering gene therapy trial has developed leukaemia, his doctors based at London's Great Ormond Street Hospital have announced. The three-year-old was of one of 10 patients treated for X-SCID: a genetic disorder whereby a mutation in the IL2RG gene leaves carriers without...
17 October 2003 - by BioNews 
US and European scientists have published results confirming that a gene therapy technique triggered leukaemia in two boys taking part in a trial at the Necker hospital, Paris. Their findings, which appear in Science, show that the virus used to deliver the therapeutic gene activated a cancer-causing gene. Eleven boys...


 

Event review: The Great Genome Sequencing Debate

05 February 2018

By Evelyn Jager

Appeared in BioNews 936

'This House believes that everyone should have their whole genome sequenced at birth.' This was the motion discussed at The Great Genome Sequencing Debate at the Royal Institution on Wednesday 24 January, sponsored by the pharmaceutical firm Roche. The debate has arisen as a result of improvements in technology which means that whole genome sequencing (WGS) is now relatively affordable. At present, it only takes around 24 hours.

The debate, chaired Vivienne Parry –head of engagement at Genomics England – opened with a poll to gauge the position of the audience watching in the room and online. The room was split roughly evenly, while the online audience was two thirds in favour of the motion. I initially voted against the motion, largely based on concerns about privacy.

The panel consisted of two speakers in favour, Professor Anneke Lucassen and Dr Robert Green, and two speakers against, Dr Kat Arney and Dr Tara Clancy. I was surprised to find I was most persuaded by Professor Lucassen’s arguments. She saw WGS at birth as a resource that could be drawn on throughout the life course, as an alternative to repeated screening for various conditions and as a diagnostic and research resource.

Speaking on the issue that was my greatest concern, privacy, Dr Green presented evidence suggesting this was not well founded. He has been involved in research projects using genomic data for the past 15 years. He argued these demonstrated that genomic data can be held securely. He noted a number of benefits reported by participants in these studies, but claimed none felt they had been harmed by sharing their data. However, Dr Clancy raised the issue that this would not necessarily translate to the general public.

Again, I found Dr Lucassen’s position persuasive on this issue. She pointed out that there is already a great deal of medical information out there, but we don’t feel concerned about this, giving several examples such as the data from heel-prick tests. She also highlighted the strangeness of feeling we have a right to our genomic data, when we do not experience this feeling about other medical data, such as X-rays. While medical data is sensitive and, if it were to get into the wrong hands, potentially dangerous, she suggested that there was nothing particularly special about genomic data compared to any other sort. She went on to suggest the key issue is how genomics is framed in current discussions.

The need to reframe the discourse around genomics, moving away from a deterministic narrative to a probabilistic one, was a central theme of the debate. This was picked up by Dr Arney in particular, who was clearly passionate about dispelling the deterministic narrative. She gave numerous examples of cases where genomic information does not translate to the phenotype. For example, the 'superheroes' whose genetic information suggests they should have a disease, but who are actually well, and 'knockouts' who are missing certain pieces of genetic information, but still have traits thought to be associated with this information.

The debate ended with some convergence. Dr Lucassen noted 'We're not that far from each other really', much to the (mock) dismay of the chair. All agreed that there is no benefit to sequencing and interpreting the whole genome of the entire population, due to the cost and uncertainty involved in this. Similarly, all appreciated that there are some risks in collecting the data, such as privacy concerns, but those in favour did not see this as any riskier than other kinds of medical data. 

The audience was polled again. There was a noticeable shift in the room towards the motion, although there was still a significant proportion against. I continued to vote against, but my reasons for doing so had changed. I was convinced that the privacy risks might not be as significant as I first thought, but voted against the motion on the grounds of cost and benefit. If WGS is to be carried out under the NHS, as argued for by Dr Lucassen, it needs to be demonstrated that this is a good use of NHS funds.

This was the position of Dr Arney, who pointed out there are a range of health interventions that we know have a positive effect, but are not offered on the NHS because they are too expensive. Given this, it does not seem appropriate to support funding for WGS unless it would yield a clear benefit. At present, Dr Green noted, no such cost-benefit analysis has taken place.

This debate is largely hypothetical at this point, as there are no serious considerations of population-wide WGS within the NHS now. Indeed, Vivienne Parry suggested such a thing is still 'light-years away', but emphasised the importance of having such conversations before it became a serious consideration, while there is still time to do so.

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

12 February 2018 - by Ruth Retassie 
Nebula Genomics, a new firm founded by geneticists, has announced its plan to sequence customers’ genomes cheaply and allow them to sell their own genomic information for digital money...

02 October 2017 - by Sandy Starr 
What do patients and laypeople think and know about genome editing and its implications? What are the best ways for experts and others to discuss genome editing in public, so as to improve public understanding and avoid confusion? The Progress Educational Trust has set out to answer these questions, with its 'Basic Understanding of Genome Editing' project....
18 September 2017 - by Professor Becki Bennett 
A public event held on 11 September 2017, Manchester by the Progress Educational Trust...
21 August 2017 - by Dr Loredana Guglielmi 
US researchers have developed a new blood test to detect cancer-related DNA alterations before patients experience symptoms...


 

Radio review: Science in Action - CRISPR immunity

05 February 2018

By Theofanis Michailidis

Appeared in BioNews 936

As a law graduate with a special interest in medical law and bioethics, I admit to having limited scientific background knowledge. Understanding a new scientific procedure or medical treatment can be challenging: often I will spend considerable time researching scientific terms and how a procedure works before fully grasping what a scientific article or research paper is talking about.

When I discovered that I would be reviewing a programme on how the human immune system could dampen the effects of the Cas9 protein, (part of the CRISPR/Cas9 approach to genome editing) if it were ever used in human therapies, I was mentally prepared for intensive research on understanding even the basic terms used in the programme.

However, much to my surprise, the BBC World Service's series Science in Action never made me feel that my lack of scientific knowledge would affect my understanding of the conversation.The section of the programme discussing human immune system response to the DNA-cutting protein Cas9 was a conversation between the host Roland Pease, and Professor Matthew Porteus, a professor of paediatrics in Stanford University.

The main point of discussion was based on the recent research from Stanford, which explores whether our immune system could get in the way of efforts to use genome editing to treat genetic conditions. When Cas9 was mentioned, I was worried that this was the moment where things would stop making sense. However, Professor Porteus provided a reassuring explanation, clarifying that Cas9 is a revolutionary tool for genome editing that allows us to make changes in the DNA of cells, with the potential to cure diseases. 

The conversation became even more interesting when the issues that could hinder the use of Cas9 were discussed. Cas9 is a protein derived from bacteria, and our immune systems may naturally generate an immune response to eliminate it, creating the possibility that our bodies have already built up immunity to the protein.

Professor Porteus did well to give the necessary information, explaining how the immune system will respond and attack a foreign protein introduced into the body. He explained that blood from healthy adults was screened and found to contain antibodies which would recognise two forms of the protein, indicating a pre-existing immunity to Cas9 (see BioNews 933).

I was very intrigued when Professor Porteus stated that the results indicated that 70 percent of the adults had pre-existing antibodies for both forms of Cas9. Although my initial question was whether these findings meant that Cas9 would not be useful in humans, the host decided not to probe this until later on. Instead, Pease opted to ask about what the possible effects of injecting the protein in him would be. While Professor Porteus could not give an accurate answer, as the findings at that point were not sufficient, he did well to provide the audience with all the possibilities, and the different reactions the body could have.

I was delighted when Pease voiced my question on whether these findings meant that Cas9 would not have practical value in human therapies. Even more satisfying was Professor Porteus' response and positive mentality with regards to the issues discussed. It was fascinating to see that genome editing scientists are optimistic about working around the issues of Cas9, as the potential that CRISPR approaches have to offer are not hindered by this obstacle.

It is easy to assume that failure is uncommon in science. Before I took an interest in medical law and bioethics I always thought that failed attempts when testing or creating new medical procedures were at a minimum. However, this is far from the truth, as unsuccessful attempts or issues arising during research and experimentation are not uncommon - especially with regard to genome editing. This radio programme is a refreshing view on what is actually going on in the working life of a genome editing scientist.

Overall, the podcast was unexpectedly easy-to-follow conversation on a not-so-easy subject. The level of detail was well-judged: the audience was provided with enough background information on the practice, the possibilities of it and an insight into its future. I was especially impressed with the well-thought-out questions the host asked, and the order in which he asked them, helping listeners keep up and stay engaged with the conversation.

The fact that the conversation is only seven minutes long means that it is possible to listen to it more than once if so desired. The subject discussed is an interesting one, and with the information and further available sources given, if interested, it is possible for anyone to look further into genome editing.

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

15 January 2018 - by Rikita Patel 
The human adaptive immune response against the Cas9 protein - part of the CRISPR genome editing system – may pose a barrier to new therapies, suggests a new study...


 

Book Review: The Telomere Effect - A Revolutionary Approach to Living Younger, Healthier, Longer

05 February 2018

By Dr Jess Buxton

Senior Lecturer in Medical Genetics, Kingston University London and Trustee, Progress Educational Trust

Appeared in BioNews 936

The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer

By Professor Elizabeth Blackburn and Professor Elissa Epel

Published by Orion Spring

ISBN-10: 1780229038, ISBN-13: 978-1780229034

Buy this book from Amazon UK


We are already into the second month of 2018, so if you made New Year's resolutions then the chances are that, like me, you've long ditched them – especially any regarding your health. It seems that changing old habits is hard, even those that we know will increase our risk of succumbing to disease and disability. And what exactly constitutes a 'healthy' lifestyle anyway?

'The Telomere Effect', published last year, views this subject through the lens of the latest research into the biology of ageing. The eponymous telomere is the protective structure found at the ends of our chromosomes, the bundles of genetic material found in almost all of our body cells. Telomeres get shorter as we age, but the rate at which this happens is influenced by a host of genetic and lifestyle factors (see BioNews 885). Or, as the publicity blurb for the book put it: 'Have you ever wondered why some 60-year olds look and feel like 40-year olds and why some 40-year olds appear more like 60-year olds?'

To answer this question, Nobel-prize-winning telomere researcher Professor Elizabeth Blackburn and health psychologist Professor Elissa Epel, both at the University of California, San Francisco, have trawled the scientific literature and summarised an impressive number of recent research studies – the findings of which, in most cases, would otherwise be inaccessible behind the journals' paywalls. Perhaps unsurprisingly, regular exercise, a 'Mediterranean-style' diet, good sleep habits and taking measures to reduce the impact of psychological stress are all associated with a slower rate of cellular ageing. But the authors also point to growing evidence that our early life experiences and social connections in adulthood are also equally important for successful ageing.

The book is written in a jargon-free, engaging style, and starts with a broad overview of telomere science and the latest findings of research into the ageing process. It then asks the reader to assess their own 'telomere trajectory', by answering questions on a range of behaviours that impact on mental and physical health. It follows this up with practical recommendations for lifestyle changes associated with a slower rate of telomere shortening, in the form of 'renewal labs' at the end of each chapter.

Professors Blackburn and Epel also take time to warn readers away from untested anti-ageing products that claim to work by lengthening telomeres. These, they say, are likely to be at best ineffective, and at worst may increase the risk of cancer. This is because once a cell's telomeres reach a critically short length, it will usually stop dividing and making new cells, and will eventually die. In this way, short telomeres act as 'the canary in the coal mine', making sure that old cells with damaged DNA are taken out of service, rather than continuing to grow in an uncontrolled, potentially cancerous way.

This book will appeal to those who prefer their health information to be both evidence-based and achievable – for example, in the chapter on physical activity the authors state that people who exercise have longer telomeres and better metabolic health. But they also point out that the telomeres of endurance athletes are not much longer than those of people who engage in moderate exercise, so 'we don't need to aspire to extremes'.

Moving on from cells and individuals, the final section of the book asks what studies of telomere maintenance can tell us about the social factors that affect human health and happiness. It contains some fascinating accounts of studies of telomere length and its association with a person's neighbourhood, income, social connections, prenatal environment and childhood experiences. As with the earlier sections on the associations between telomeres and lifestyle factors, there is less information on the biological mechanisms that may underlie these intriguing observations. However this is a limitation of the field itself, rather than any omission on the authors' part – as is often the case, more research is needed. And their conclusion that these findings should act as a rallying call to address social inequalities can hardly be argued with.

Overall, this book is a well-written, scientifically rigorous and user-friendly guide to making simple and enduring lifestyle changes that may counteract genetic predisposition to age-related disease. Or, as the authors put it in their concluding chapter: 'Our genes are like computer hardware; we cannot change them. Our epigenome, of which telomeres are a part, is like software, which requires programming. We are the programmers of the epigenome.'


Buy The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer from Amazon UK.

SOURCES & REFERENCES

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

23 January 2017 - by Matthew Thomas 
Older women who take little exercise and live a more sedentary lifestyle have disproportionately older DNA, researchers have found...
29 June 2015 - by Isobel Steer 
Residents of noisy and high-crime neighbourhoods are over a decade older biologically compared with those who live in low-crime areas, according to recent research...
08 December 2014 - by Dr Nicoletta Charolidi 
Women who consume a Mediterranean-style diet are less likely to show evidence of 'cellular ageing' and therefore more likely to live longer, say US researchers...

 

 

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