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

Poor diet is a factor in one in five deaths, global disease study reveals

Study compiling data from every country finds people are living longer but millions are eating wrong foods for their health

Poor diet is a factor in one in five deaths around the world, according to the most comprehensive study ever carried out on the subject.

Millions of people are eating the wrong sorts of food for good health. Eating a diet that is low in whole grains, fruit, nuts and seeds and fish oils and high in salt raises the risk of an early death, according to the huge and ongoing study Global Burden of Disease.

The study, based at the Institute of Health Metrics and Evaluation at the University of Washington, compiles data from every country in the world and makes informed estimates where there are gaps. Five papers on life expectancy and the causes and risk factors of death and ill health have been published by the Lancet medical journal.

It finds that people are living longer. Life expectancy in 2016 worldwide was 75.3 years for women and 69.8 for men. Japan has the highest life expectancy at 84 years and the Central African Republic has the lowest at just over 50. In the UK, life expectancy for a man born in 2016 is 79, and for a woman 82.9.

Diet is the second highest risk factor for early death after smoking. Other high risks are high blood glucose which can lead to diabetes, high blood pressure, high body mass index (BMI) which is a measure of obesity, and high total cholesterol. All of these can be related to eating the wrong foods, although there are also other causes.

causes of death graphic

This is really large, Dr Christopher Murray, IHMEs director, told the Guardian. It is amongst the really big problems in the world. It is a cluster that is getting worse. While obesity gets attention, he was not sure policymakers were as focused on the area of diet and health as they needed to be. That constellation is a really, really big challenge for health and health systems, he said.

The problem is often seen as the spread of western diets, taking over from traditional foods in the developing world. But it is not that simple, says Murray. Take fruit. It has lots of health benefits but only very wealthy people eat a lot of fruit, with some exceptions.

Sugary drinks are harmful to health but eating a lot of red meat, the study finds, is not as big a risk to health as failing to eat whole grains. We need to look really carefully at what are the healthy compounds in diets that provide protection, he said.

undernourishment graphic

Prof John Newton, director of health improvement at Public Health England, said the studies show how quickly diet and obesity-related disease is spreading around the world. I dont think people realise how quickly the focus is shifting towards non-communicable disease [such as cancer, heart disease and stroke] and diseases that come with development, in particular related to poor diet. The numbers are quite shocking in my view, he said.

The UK tracks childhood obesity through the school measurement programme and has brought in measures to try to tackle it. But no country in the world has been able to solve the problem and it is a concern that we really need to think about tackling globally, he said.

Today, 72% of deaths are from non-communicable diseases for which obesity and diet are among the risk factors, with ischaemic heart disease as the leading cause worldwide of early deaths, including in the UK. Lung cancer, stroke, lung disease (chronic obstructive pulmonary disorder) and Alzheimers are the other main causes in the UK.

The success story is children under five. In 2016, for the first time in modern history, fewer than 5 million children under five died in one year a significant fall compared with 1990, when 11 million died. Increased education for women, less poverty, having fewer children, vaccinations, anti-malaria bed-nets, improved water and sanitation are among the changes in low-income countries that have brought the death rate down, thanks to development aid.

People are living longer but spending more years in ill health. Obesity is one of the major reasons. More than a billion people worldwide are living with mental health and substance misuse disorders. Depression features in the top 10 causes of ill health in all but four countries.

Our findings indicate people are living longer and, over the past decade, we identified substantial progress in driving down death rates from some of the worlds most pernicious diseases and conditions, such as under age-five mortality and malaria, said Murray Yet, despite this progress, we are facing a triad of trouble holding back many nations and communities obesity, conflict, and mental illness, including substance use disorders.

In the UK, the concern is particularly about the increase in ill-health that prevents people from working or having a fulfilling life, said Newton. A man in the UK born in 2016 can expect only 69 years in good health and a woman 71 years.

This is yet another reminder that while were living longer, much of that extra time is spent in ill-health. It underlines the importance of preventing the conditions that keep people out of work and put their long term health in jeopardy, like musculoskeletal problems, poor hearing and mental ill health. Our priority is to help people, including during the crucial early years of life and in middle age, to give them the best chance of a long and healthy later life, he said.

Read more: https://www.theguardian.com/society/2017/sep/14/poor-diet-is-a-factor-in-one-in-five-deaths-global-disease-study-reveals

Terry Pratchett’s unfinished novels destroyed by steamroller

Unpublished works are lost for ever with crushing of computer hard drive as the late fantasy novelist had instructed

The unfinished books of Sir Terry Pratchett have been destroyed by a steamroller, following the late fantasy novelists wishes.

Pratchetts hard drive was crushed by a vintage John Fowler & Co steamroller named Lord Jericho at the Great Dorset Steam Fair, ahead of the opening of a new exhibition about the authors life and work.

Pratchett, famous for his colourful and satirical Discworld series, died in March 2015 after a long battle with Alzheimers disease.

After his death, fellow fantasy author Neil Gaiman, Pratchetts close friend and collaborator , told the Times that Pratchett had wanted whatever he was working on at the time of his death to be taken out along with his computers, to be put in the middle of a road and for a steamroller to steamroll over them all.

On Friday, Rob Wilkins, who manages the Pratchett estate, tweeted from an official Twitter account that he was about to fulfil my obligation to Terry along with a picture of an intact computer hard drive following up with a tweet that showed the hard drive in pieces.

The symbolism of the moment, which captured something of Pratchetts unique sense of humour, was not lost on fans, who responded on Twitter with a wry melancholy, though some people expressed surprise that the author who had previously discussed churning through computer hardware at a rapid rate would have stored his unfinished work on an apparently older model of hard drive.

The hard drive will go on display as part of a major exhibition about the authors life and work, Terry Pratchett: HisWorld, which opens at the Salisbury museum in September.

The author of over 70 novels, Pratchett was diagnosed with Alzheimers disease in 2007.

He became an advocate for assisted dying, giving a moving lecture on the subject, Shaking Hands With Death, in 2010, and presenting a documentary for the BBC called Terry Pratchett: Choosing to Die.

He continued to write and publish, increasingly with the assistance of others, until his death in 2015. Two novels were published posthumously: The Long Utopia (a collaboration with Stephen Baxter) and The Shepherds Crown, the final Discworld novel.

The Salisbury museum exhibition will run from 16 September until 13 January 2018.

Read more: https://www.theguardian.com/books/2017/aug/30/terry-pratchett-unfinished-novels-destroyed-streamroller