Matt Ellison was seven when his father was diagnosed with Huntington’s disease. The condition – which is progressive, incurable and invariably fatal – took 15 years to kill John Ellison.

The impact on Matt’s life was profound. His father, who had inherited the disease from his mother, found he could no longer concentrate enough to hold down his job as an engineer at Jaguar. Later he began to lose the power of movement and, eventually, lost his ability to speak. At his local school Matt was mocked because of his father’s odd, uncoordinated gait. The taunting got so bad that Matt stopped attending. “I stayed at home and helped Mum look after Dad,” he recalls.

Then in 2007, when Matt reached 18, he decided to find out whether he faced a similar fate. He was tested and told: yes, he had the Huntington’s gene. A few years later his father died, aged 55.

“I had had time to prepare myself, but it still hits you hard when you are told you are positive,” says Matt. “I had wanted to be negative as much for my mum, who had gone through enough pain.”

For Matt, and thousands of others who have been told they have inherited this affliction, the future would appear bleak, a prospect of inexor able physical and mental decline. The Huntington’s gene is remorseless in its impact.

But recently this dark outlook has brightened. Scientists believe they are closing in on a treatment to control Huntington’s worst effects.

“We recently tested a new drug, called RG6042, that appears to be safe from our first phase-one trial and which reduces levels of the toxic protein that builds up in patients’ brain cells and is believed to trigger the disease,” says Huntington’s expert Professor Sarah Tabrizi of University College London. “It’s a great step forward.”

A big hurdle remains, however: scientists still have to show that RG6042 actually delays or halts the progression of the disease once it has taken hold of patients’ brain cells. It may reduce levels of the mutant protein, but will it actually slow or stop the onset of symptoms? Will it help those in the later stages of the disease, or aid those who have just begun to display symptoms?

These critically important questions should be answered by a major trial that has just been launched. More than 600 patients will be involved – the first has already been recruited – and the trial, backed by the pharmaceuticals giant Roche, is set to begin in Europe in a few months’ time.

“It will take two years to complete, but it should tell us if we have a winner on our hands: a drug that could potentially improve patients’ lives,” says Tabrizi. “I am rightly cautious but hopeful.”

As for the thousands whose lives have been blighted by Huntington’s, and for families touched by the disease, the prospect of effective treatment is almost overwhelming. This point is stressed by Matt Ellison, who now runs a charity that helps young adults from families affected by Huntington’s.

“There is so much hope riding on this trial,” he says. “The whole Huntington’s community is watching. I am trying not to get too excited. I know there is a good chance we are going to change the way we treat Huntington’s over the next 15 years, but I don’t know if that change will come in time to help me. I am going to be 30 this year.”

Huntington’s disease was first identified in the US in 1872 by George Huntington, a doctor’s son who used to ride with his father on his rounds in Long Island and who recalled coming across “two women, both tall, thin, almost cadaverous, both bowing, twisting, grimacing”. The young Huntington later qualified as a doctor and continued his interest in the condition, which he linked to other “shakers” (as he termed people with the condition). He concluded that there must be an inherited link by which the disease is passed from parent to offspring.

Neuroscientist Sarah Tabrizi. Photograph: UCL

This connection has since been identified as a single mutant gene. A person who inherits one will invariably develop Huntington’s disease, while their children will each have a 50% chance of succumbing. Such genes are called dominant genes.

It is estimated that about one in 8,000 people carry the gene, which affects men and women in equal proportions. In the UK it is believed that there are between 6,000 and 10,000 people with Huntington’s disease, and that another 25,000 are at risk of developing it.

Typically symptoms start between the ages of 30 and 50, with memory problems and depression followed by deteriorating coordination, unsteady gait and uncoordinated, jerky body movements. Speech is lost, psychiatric problems arise, then dementia sets in before death occurs.

Among those affected by Huntington’s is the writer Charlotte Raven, whose first symptoms were diagnosed five years ago. “These days I struggle to carry out simple tasks, so I am completely dependent on carers,” she told the Observer. “I can’t even make a sandwich or read – so I spend hours watching the news while my friends go about their lives. I have never been more lonely. I would cry, but Huntington’s has blunted my emotions.”

The cruel impact of the disease is made worse by the fact that many carriers of the Huntington gene have had children before they discover that they have inherited the condition. Husbands and wives are then left to watch not just a spouse sicken and die but their children as well.

Consider the story of Mark Newnham. “My family was completely unaware we were affected by the disease. Then in 2007 my father’s uncle died of the disease and Dad realised he was at risk. It turned out his own father had the disease, but for some reason it was not diagnosed. Instead, pneumonia was given as the cause of his death.”

Mark’s father took the test and found he had the gene. “In retrospect I can see even then that he was forgetful and slow when talking on the phone. At the time I just thought that is what dads were like.”

Mark’s father is now in the later stages of the disease, and in addition to physical problems has suffered severe depression and anxiety, which are treated with powerful mood stabilisers. “We had no idea this disease was running in the family,” says Mark, who is now 32 and has also tested positive for the gene. Other close relatives have found that they are living in the shadow of Huntington’s as a result.

“This is a truly terrible disease,” says Tabrizi. “It is like Parkinson’s, motor neurone disease and schizophrenia rolled into one. It devastates families. I have seen households in which mothers have lost husbands and all their children to Huntington’s. People will watch an affected parent suffer and die knowing that they may carry the gene themselves.”

Mark Newnham and his cocker spaniel Lenny.

This point was underlined last year by Danish researchers, who found that people with Huntington’s are nearly nine times more likely to attempt suicide than individuals in the general population.

For much of the 20th century, scientists struggled to understand the disease’s origins and pathways. Then, in the late 1970s, researchers discovered a community on the shores of Lake Maracaibo in Venezuela where scores of Huntington’s sufferers were living in interbred families in tin shacks and huts on stilts. All were descendants of María Concepción Sota, who had brought el mal to the area in the 1860s.

A team of US doctors, nurses, geneticists and neurologists arrived and took blood samples, carried out diagnoses and worked out exact relationships between local people, many of them in the final twisting, writhing stages of Huntington’s disease. Then the data was brought to Professor Jim Gusella, director of the Center for Human Genetic Research at Massachusetts general hospital, in Boston.

Gusella quickly mapped the location of the gene on a particular human chromosome (chromosome 4, to be precise). However, it took a further 10 years to work out the exact location of the gene and to sequence its precise structure.

A remarkable piece of scientific detective work revealed there are two versions of the gene. A normal nonmutant version directs the manufacture of a protein called huntingtin, which we now know is involved in brain development. However, in some families a mutant version of this gene produces a toxic form of huntingtin. This accumulates in brain cells until it triggers the disease in mid-life.

Uncovering the precise nature of this pathway raised hopes that drugs could soon be developed to block the creation of mutant huntingtin. But the brain’s complexity thwarted early efforts. Indeed it has only been in the past few years that scientists have developed techniques to allow them to create drugs that can get into the brain. This is done via an injection that directly into the spinal fluid and is called a lumbar puncture. It is similar to that used to administer epidural pain relief during labour.

“I would certainly have been disappointed if I had been told 25 years ago that we would only now be at this stage of developing a possible treatment for Huntington’s,” Gusella told the Observer. “But this disease has proved to be extraordinarily complex. Fortunately we now have much better tools for tackling it. So I am hopeful we are going to move much faster.”

The discovery of the Huntington’s gene may not have resulted in the immediate creation of treatments, but it did lead to one important development: a test that could identify those who would succumb to the condition in later life. Previously, affected individuals were only spotted at the stage when their symptoms were manifesting themselves.

Some researchers envisaged a future in which tests would be offered to at-risk men and women who were planning families. Those who registered positive would be persuaded not to have children. Thus Huntington’s disease would slowly be eliminated from the human gene pool.

Writer Charlotte Raven. Photograph: Katherine Anne Rose/The Observer

But this idea ignores the fact that many people from affected families are terrified they might die in the same grim fashion as their parents. As a result, most people at risk of the disease choose not to have the test. And many genetic counsellors accept this decision, says Anna Middleton, head of society and ethics research at the Wellcome Genome Campus in Cambridge.

“Managing the uncertainty is one of the most difficult things to cope with for people from affected families. The whole condition is a myriad of uncertainties. People have to cope with so many factors – the experience of seeing the disease in relatives, the acceptance of uncertainty, and being able to live in the moment.”

Others do take the plunge, however. For Matt Ellison it has meant being able to have a child, Joey – now 20 months old – with his partner Marianna. “We know that he is free of the Huntington’s gene, thanks to a technique called pre-implantation genetic diagnosis, which allows you to create an embryo that lacks my mutant chromosome 4.”

Mark Newnham also attempted to have children with his partner using the same technique, but without success. “Adoption is a possibility but people with my condition tend to be at the bottom of lists of potential foster parents,” he says. “On the other hand, there is now the prospect of a drug that will stop Huntington’s being a death sentence.”

Drug RG6042 is made up of a snippet of DNA, the material from which our genes are constructed, and it has been designed by scientists at Ionis Pharmaceuticals in Carlsbad, California. It is known as an “anti-sense drug” and it blocks the operation of the mutant and nonmutant versions of Huntington’s gene in brain cells, thus halting their ability to create either form of huntingtin. In 2015 Tabrizi began a phase-one safety trial using the drug on 46 people with the disease and presented her results at a conference in March 2017.

There were no harmful side-effects, she told delegates. More importantly she found that levels of mutant huntingtin were reduced in patients and, crucially, patients given the highest doses of RG6042 saw the greatest reduction in levels of toxic protein.

It was a dramatic presentation. This was the first time a neurological defect had been tackled successfully at a molecular level. People at the conference started crying, the journal Nature reported.

Such jubilation is understandable. Most delegates knew someone touched by the condition and this was the first real sign that the disease might be tackled successfully. Neurologist John Hardy of University College London was particularly impressed. “I think this is, potentially, the biggest breakthrough in neurodegenerative disease in the past 50 years,” he told the BBC.

Tabrizi is more cautious. “There is no doubt that this is a major step forward, but we are not there yet. We need to see improvements in patients’ symptoms. We don’t know yet if that will happen, but we aim to find out with this trial.”

A total of 660 Huntington patients will be involved in the study, which will be carried out in 15 countries including the UK, US, Canada and Spain. Of these patients, 440 will get RG6042 and 220 will be given a placebo.

“For two years, the drug or the placebo will be injected, at regular intervals, into the base of each patient’s spine,” says Tabrizi. “Their spinal fluid will then carry the drug into their brains.”

At the same time, patients will also be given cognitive tests, psychiatric assessments and neurological check-ups by researchers to assess whether the drug is having an effect on their symptoms and to check if their physical and mental decline is being halted or possibly reversed. After two years this data will be collated and studied for hard evidence that RG6042 is an effective treatment for Huntington’s disease.

“I have looked after patients with Huntington’s for more than 20 years and have seen the awful things it does,” says Tabrizi. “All of us working in the field are absolutely passionate about finding a treatment, but we have to manage people’s expectations carefully. We will know where we are in two years, but I am cautiously hopeful.”

Woody Guthrie’s legacy

The US folksinger Woody Guthrie died in October 1967, a victim of Huntington’s disease. Guthrie had inherited the gene from his mother, Nora. Her increasingly erratic behaviour had led to her committal to a mental home in 1927, when Woody and his siblings were abandoned. His subsequent experiences living with the downtrodden of the US Depression formed the core of his work and inspired many of his songs.

Woody Guthrie. Photograph: Eric Schaal/Time & Life Pictures/Getty Image

Then, in his 30s, Guthrie began to display symptoms of Huntington’s disease and slowly descended into worsening states of emaciation, exhaustion and dementia until he died, aged 55.

His second wife, Marjorie, decided not enough had been done to help her former husband. Nor was sufficient effort being made to fight the disease in general. So she set up the Committee to Combat Huntington’s Chorea. It lobbied the US government to fund the battle against the disease and in 1976 Congress created a federal Huntington’s disease commission to investigate the depth of the problem in the US. Marjorie was appointed its chair. As part of the evidence given to it, the commission learned of the story of the Maracaibo colony of Huntington’s sufferers and was instrumental in backing the first expeditions there – in the long term, this led to the discovery of the Huntington’s gene.