Excitement as trial shows Huntington’s drug could slow progress of disease

Hailed as enormously significant, results in groundbreaking trial are first time a drug has been shown to suppress effects of Huntingtons genetic mutation

A landmark trial for Huntingtons disease has announced positive results, suggesting that an experimental drug could become the first to slow the progression of the devastating genetic illness.

The results have been hailed as enormously significant because it is the first time any drug has been shown to suppress the effects of the Huntingtons mutation that causes irreversible damage to the brain. Current treatments only help with symptoms, rather than slowing the diseases progression.

Q&A

What is Huntington’s disease?

Huntingtons disease is a congenital degenerative condition caused by a single defective gene. Most patients are diagnosed in middle age, with symptoms including mood swings, irritability and depression. As the disease progresses, more serious symptoms can include involuntary jerky movements, cognitive difficulties and issues with speech and swallowing.

Currently there is no cure for Huntington’s, although drugs exist which help manage some of the symptoms. It is thought that about 12 people in 100,000 are affected by Huntington’s, and if a parent carries the faulty gene there is a 50% chance they will pass it on to their offspring.

Prof Sarah Tabrizi, director of University College Londons Huntingtons Disease Centre who led the phase 1 trial, said the results were beyond what Id ever hoped … The results of this trial are of ground-breaking importance for Huntingtons disease patients and families, she said.

The results have also caused ripples of excitement across the scientific world because the drug, which is a synthetic strand of DNA, could potentially be adapted to target other incurable brain disorders such as Alzheimers and Parkinsons. The Swiss pharmaceutical giant Roche has paid a $45m licence fee to take the drug forward to clinical use.

Huntingtons is an incurable degenerative disease caused by a single gene defect that is passed down through families.

The first symptoms, which typically appear in middle age, include mood swings, anger and depression. Later patients develop uncontrolled jerky movements, dementia and ultimately paralysis. Some people die within a decade of diagnosis.

Most of our patients know whats in their future, said Ed Wild, a UCL scientist and consultant neurologist at the National Hospital for Neurology and Neurosurgery in London, who administered the drug in the trial.

The mutant Huntingtons gene contains instructions for cells to make a toxic protein, called huntingtin. This code is copied by a messenger molecule and dispatched to the cells protein-making machinery. The drug, called Ionis-HTTRx, works by intercepting the messenger molecule and destroying it before the harmful protein can be made, effectively silencing the effects of the mutant gene.

How the drug works to slow the progress of Huntington’s disease

To deliver the drug to the brain, it has to be injected into the fluid around the spine using a four-inch needle.

Prof John Hardy, a neuroscientist at UCL who was not involved in the trial, said: If Id have been asked five years ago if this could work, I would have absolutely said no. The fact that it does work is really remarkable.

The trial involved 46 men and women with early stage Huntingtons disease in the UK, Germany and Canada. The patients were given four spinal injections one month apart and the drug dose was increased at each session; roughly a quarter of participants had a placebo injection.

After being given the drug, the concentration of harmful protein in the spinal cord fluid dropped significantly and in proportion with the strength of the dose. This kind of closely matched relationship normally indicates a drug is having a powerful effect.

For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated, said Tabrizi. This is probably the most significant moment in the history of Huntingtons since the gene [was isolated].

The trial was too small, and not long enough, to show whether patients clinical symptoms improved, but Roche is now expected to launch a major trial aimed at testing this.

If the future trial is successful, Tabrizi believes the drug could ultimately be used in people with the Huntingtons gene before they become ill, possibly stopping symptoms ever occurring. They may just need a pulse every three to four months, she said. One day we want to prevent the disease.

The drug, developed by the California biotech firm Ionis Pharmaceuticals, is a synthetic single strand of DNA customised to latch onto the huntingtin messenger molecule.

The unexpected success raises the tantalising possibility that a similar approach might work for other degenerative brain disorders. The drugs like Lego, said Wild. You can target [any protein].

For instance, a similar synthetic strand of DNA could be made to target the messenger that produces misshapen amyloid or tau proteins in Alzheimers.

Huntingtons alone is exciting enough, said Hardy, who first proposed that amyloid proteins play a central role in Alzheimers. I dont want to overstate this too much, but if it works for one, why cant it work for a lot of them? I am very, very excited.

Prof Giovanna Mallucci, associate director of UK Dementia Research Institute at the University of Cambridge, described the work as a tremendous step forward for individuals with Huntingtons disease and their families.

Clearly, there will be much interest into whether it can be applied to the treatment of other neurodegenerative diseases, like Alzheimers, she added. However, she said that in the case of most other disorders the genetic causes are complex and less well understood, making them potentially harder to target.

About 10,000 people in the UK have the condition and about 25,000 are at risk. Most people with Huntingtons inherited the gene from a parent, but about one in five patients have no known family history of the disease.

The full results of the trial are expected to be published in a scientific journal next year.

Read more: https://www.theguardian.com/science/2017/dec/11/excitement-as-huntingtons-drug-shown-to-slow-progress-of-devastating-disease

Rule that patients must finish antibiotics course is wrong, study says

Experts suggest patients should stop taking the drugs when they feel better rather than completing their prescription

Telling patients to stop taking antibiotics when they feel better may be preferable to instructing them to finish the course, according to a group of experts who argue that the rule long embedded in the minds of doctors and the public is wrong and should be overturned.

Patients have traditionally been told that they must complete courses of antibiotics, the theory being that taking too few tablets will allow the bacteria causing their disease to mutate and become resistant to the drug.

But Martin Llewelyn, a professor in infectious diseases at Brighton and Sussex medical school, and colleagues claim that this is not the case. In an analysis in the British Medical Journal, the experts say the idea that stopping antibiotic treatment early encourages antibiotic resistance is not supported by evidence, while taking antibiotics for longer than necessary increases the risk of resistance.

There are some diseases where the bug can become resistant if the drugs are not taken for long enough. The most obvious example is tuberculosis, they say. But most of the bacteria that cause people to become ill are found on everybodys hands in the community, causing no harm, such as E coli and Staphylococcus aureus. People fall ill only when the bug gets into the bloodstream or the gut. The longer such bacteria are exposed to antibiotics, the more likely it is that resistance will develop.

The experts say there has been too little research into the ideal length of a course of antibiotics, which also varies from one individual to the next, depending in part on what antibiotics they have taken in the past.

In hospital, patients can be tested to work out when to stop the drugs. Outside hospital, where repeated testing may not be feasible, patients might be best advised to stop treatment when they feel better, they say. That, they add, is in direct contravention of World Health Organisation advice.

Other experts in infectious diseases backed the group. I have always thought it to be illogical to say that stopping antibiotic treatment early promotes the emergence of drug-resistant organisms, said Peter Openshaw, president of the British Society for Immunology.

This brief but authoritative review supports the idea that antibiotics may be used more sparingly, pointing out that the evidence for a long duration of therapy is, at best, tenuous. Far from being irresponsible, shortening the duration of a course of antibiotics might make antibiotic resistance less likely.

Alison Holmes, a professor of infectious diseases at Imperial College London, said a great British authority, Prof Harold Lambert, had made the same point in a Lancet article entitled Dont keep taking the tablets as early as 1999. It remains astonishing that apart from some specific infections and conditions, we still do not know more about the optimum duration of courses or indeed doses in many conditions, yet this dogma has been pervasive and persistent.

Jodi Lindsay, a professor of microbial pathogenesis at St Georges, University of London, said it was sensible advice. The evidence for completing the course is poor, and the length of the course of antibiotics has been estimated based on a fear of under-treating rather than any studies, she said. The evidence for shorter courses of antibiotics being equal to longer courses, in terms of cure or outcome, is generally good, although more studies would help and there are a few exceptions when longer courses are better for example, TB.

But the Royal College of GPs expressed concerns. Recommended courses of antibiotics are not random, said its chair, Prof Helen Stokes-Lampard. They are tailored to individual conditions and in many cases, courses are quite short for urinary tract infections, for example, three days is often enough to cure the infection.

We are concerned about the concept of patients stopping taking their medication midway through a course once they feel better, because improvement in symptoms does not necessarily mean the infection has been completely eradicated. Its important that patients have clear messages and the mantra to always take the full course of antibiotics is well known. Changing this will simply confuse people.

The UKs chief medical officer, Prof Dame Sally Davies, said: The message to the public remains the same: people should always follow the advice of healthcare professionals. To update policies, we need further research to inform them.

[The National Institute for Health and Care Excellence] is currently developing guidance for managing common infections, which will look at all available evidence on appropriate prescribing of antibiotics.

The Department of Health will continue to review the evidence on prescribing and drug-resistant infections, as we aim to continue the great progress we have made at home and abroad on this issue.

Read more: https://www.theguardian.com/society/2017/jul/26/rule-patients-must-finish-antibiotics-course-wrong-study-says

Meningitis vaccine may also cut risk of ‘untreatable’ gonorrhoea, study says

Bacteria causing two different illnesses belong to the same family and share much of the same genetic code providing unexpected cross protection

Hopes to fight untreatable strains of gonorrhoea have risen after it emerged that a new vaccine against meningitis unexpectedly reduced the risk of people getting the sexually transmitted infection.

Some strains of gonorrhoea are resistant to all available drugs, making vaccine development an urgent global health priority. But according to a study in The Lancet, a vaccine has offered protection against the sexually transmitted disease for the first time.

Gonorrhoea spreads through unprotected vaginal, oral or anal sex and many of those who contract the disease experience no symptoms. If left untreated, the disease can cause infertility and can increase the transmission of HIV infection.

A New Zealand meningitis epidemic in the early 2000s prompted the mass vaccination of a million people and fortuitously set the scene for the current study. The vaccine used, known as MeNZB, was designed to protect against meningococcal group B infection the cause of the most deadly form of meningitis.

But intriguingly, over the next few years, scientists noticed fewer gonorrhoea cases than expected in those who had been vaccinated against meningitis.

Dr Helen Petousis-Harris, a vaccine specialist from the University of Auckland who led the study, was optimistic: Some types of gonorrhoea are now resistant to every antibiotic we have, and there appeared [to be] little we could do to prevent the steady march of gonorrhoea to superbug status. But now theres hope, she added.

The research team studied over 14,000 people aged 15-30 whod been diagnosed with gonorrhoea at sexual health clinics across New Zealand and who had been eligible for the MeNZB vaccine during the emergency vaccination programme. They found vaccinated individuals were over 30% less likely to develop gonorrhoea.

Despite meningitis and gonorrhoea being very different illnesses, both are caused by bacteria from the same family and share much of the same genetic code, providing a possible explanation for the cross-protection that the team observed.

More than 78 million people worldwide get gonorrhoea each year with most infections in men and women under the age of 25. It is the second most common bacterial sexually transmitted infection in the UK after chlamydia. In England alone, almost 35,000 people were affected in 2014.

British Association for Sexual Health and HIVs President, Dr Elizabeth Carlin, who was not involved in the study, was more sceptical: These early findings are to be welcomed but its important to keep in perspective that the vaccine offered only moderate protection …. an individual receiving this vaccine remains susceptible to gonorrhoea but just less so than if unvaccinated.

The MeNZB vaccine used in the current study is no longer manufactured, but Petousis-Harris has high hopes for a similar meningitis vaccine called 4CMenB, available in many countries.

Petousis-Harris was clear about what needed to happen next. We need an urgent assessment of current meningitis vaccines to see if they protect against gonorrhoea. It may be possible to eliminate many gonorrhoea infections using a vaccine with only moderate protection. It does not need to be perfect, she added.

Read more: https://www.theguardian.com/science/2017/jul/10/meningitis-vaccine-may-also-cut-risk-of-untreatable-gonorrhoea-study-says

Gluten-free diet carries increased obesity risk, warn experts

Food adapted for those with coeliac disease often has more fat and less protein, and no benefits to non-sufferers, finds research

Substituting everyday staples with gluten-free foods could increase the risk of obesity, experts have warned, after finding that such products often contain higher levels of fats than the food they aim to replace.

A gluten-free diet is essential to those with coeliac disease an auto-immune condition that is thought to affect 1% of Europeans while the regime is also proving increasingly popular among those without the disease. But while a host of gluten-free products are on the market, researchers have said they have a very different nutritional make-up to conventional staples.

There is very little [consumers] can do about it, said Joaquim Calvo Lerma of the Instituto de Investigacin Sanitaria La Fe in Spain and co-author of the research. Unfortunately consumers can [only] eat what is available on the market.

Calvo Lermas warning comes after he and his and colleagues compared 655 conventional food products to 654 gluten-free alternatives across 14 food groups including breads, pasta, breakfast cereals, biscuits and even ready meals, covering a range of brands.

The results presented at the annual meeting of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition reveal that, overall, gluten-free products were more energy-dense than their conventional counterparts.

The team found that, on average, gluten-free bread loaves had more than twice the fat of conventional loaves, while gluten-free breads in general had two to three times less protein than conventional products. Gluten-free biscuits were also found to be lower in protein but higher in fat, while gluten-free pasta had lower levels of sugar and just half of the protein of standard pasta.

Calvo Lerma warned that gluten-free foods could be contributing to an increased risk of obesity, particularly among children who are more likely to eat products like biscuits and breakfast cereals. He urged consumers to compare gluten-free products across brands to find those with the lowest fat content.

Calvo Lerma also called on manufacturers to innovate. It is the responsibility of the food industry to produce these type of gluten-free products from other materials that are much healthier or have a [more] enhanced nutritional profile than the current raw materials being used, like cornflour or potato starch, he said, pointing out that healthier products could be made, for example, using grains such as buckwheat or amaranth.

He added that manufacturers should also add more complete and clearer labels to products to highlight their nutritional content, including levels of vitamins and minerals.

Benjamin Lebwohl, from the coeliac disease centre at Columbia University, who was not involved in the research, said that the study backs up previous evidence that gluten-free foods are nutritionally suboptimal. But while a gluten-free diet is essential for coeliacs, it is not intrinsically healthy or unhealthy, he added. It depends on the choices you make as part of the gluten-free diet, he said.

Sarah Sleet, chief executive of Coeliac UK, said the latest findings tie in with the charitys own research, adding that further development of lower-fat, gluten-free products would be welcomed.

David Sanders, professor of gastroenterology at the University of Sheffield, noted that other studies have found gluten-free and conventional foods to have similar nutritional value. The jury is out, he said.

But Sanders cautioned that there is no evidence a gluten-free diet has benefits for those without gluten sensitivity or coeliac disease. Once you go into the territory of dietary restrictions without medical symptoms then you are running the gauntlet of missing out on various vitamins or minerals without realising it, he said.

Read more: https://www.theguardian.com/lifeandstyle/2017/may/11/gluten-free-diet-carries-increased-obesity-risk-warn-experts

Health report links antibiotics to risk of miscarriage

Canadian study finds taking the drugs raises chances of having a miscarriage by between 60% and 100%

Many common antibiotics may double the risk of miscarriage in early pregnancy, research has shown.

A Canadian study has found that taking the drugs raised the chances of having a miscarriage by between 60% and 100%.

The link was seen with several classes of antibiotic including macrolides, quinolones, tetracyclines, sulphonamides and metronidazole. However, nitrofurantoin, often used to treat urinary tract infections in pregnant women, had no effect on miscarriage risk. Nor did the widely used antibiotic erythromycin.

The researchers looked at data from almost 9,000 cases of miscarriage at an average time of 14 weeks into pregnancy, involving girls and women aged between 15 and 45.

The study leader, Dr Anick Brard, from the University of Montreal in Quebec, said: Infections are prevalent during pregnancy. Although antibiotic use to treat infections has been linked to a decreased risk of prematurity and low birth weight in other studies, our investigation shows that certain types of antibiotics are increasing the risk of spontaneous abortion, with a 60% to two-fold increased risk.

Women who miscarried were more likely to be older, living alone, and to have multiple health issues and infections. But all these factors were accounted for in the analysis, whose findings are published in the Canadian Medical Association Journal.

Dr Brard added: The increased risk was not seen for all antibiotics, which is reassuring for users, prescribers and policymakers.

The researchers identified a total of 182,369 pregnancies from the Quebec pregnancy cohort, a large population group from the province providing data for ongoing studies. Of these, 8,702 (4.7%) ended with an early miscarriage.

Writing in the journal, the team concluded that there was a link between some antibiotics and an increased risk of miscarriage, but added: However, residual confounding by severity of infection cannot be ruled out.

Read more: https://www.theguardian.com/society/2017/may/02/health-report-links-antibiotics-to-risk-of-miscarriage