An award winning documentary about three families who must decide whether to be tested for Huntington's disease is being screened at a documentary festival at UCL this month, followed by a panel debate including Professor Sarah Tabrizi, other experts and patients.
The lay accessible film looks at the issue, 'If you were to develop an incurable brain disorder, would you want to know?'
Huntington’s disease (HD) has been described as a genetic death sentence because of its particularly cruel characteristics. It progressively strips a person of control of muscles, reason and emotions, although not necessarily in that order.
It is caused by a mutation in a single gene, and if you have the mutation, you will develop the disease. The only unknown is when.
The film ‘Do You Really Want to Know?’ portrays the complex emotional, ethical and psychological issues that accompany predictive genetic testing.
Since there are now over 4,000 disorders with a known genetic basis, an estimated 60% of the population will experience a disease with a genetic component. As scientists get better at identifying this degenerative neurological illness "do you really want to know?" will be a question more and more will face.
Following the screening of the film, there will be a panel discussion. Panel members include Professor Sarah Tabrizi, Professor of Clinical Neurology at the National Hospital for Neurology and Neurosurgery (NHNN), the UK’s largest dedicated neurological and neurosurgical hospital, which carries out a range of research through its HD Multidisciplinary Clinic.
The film follows people who have been confronted with the difficult decision of whether or not to be tested for the HD gene. If results confirm a person does have this they will go on to develop symptoms akin to having the motor neurone disease Amyotrophic Lateral Sclerosis (ALS), Schizophrenia and Alzheimer's.
HD was one of the first diseases people could be accurately and conclusively tested for before the onset of any symptoms. Typically the first symptoms appear between the ages of 30 and 50, so many people pass the disease on before discovering they have it.
There is as yet no cure.In all three personal stories, family members describe the experience of being tested and the ramifications of that choice on their relationships with partners, children, families and friends, and how they now feel about that decision after learning their result.
One of those people is Dr Jeff Carroll. Jeff says: “You can never not know your status again. You can never turn the clock back”
Jeff was 20 years old and serving in the
With little information then available about HD, Jeff signed up for a biology course to develop his understanding on what was happening to his mum. He ended up completing a PhD with well-known HD researcher Dr Michael Hayden at the Center for Molecular Medicine and Therapeutics in
Jeff points out: “Ultimately, drugs are going to be tested in people who know their genetic status. We all want drugs to be tested in pre-symptomatic people, rather than people with overt signs of disease. This requires a large pool of people who know their genetic status but don't yet have symptoms”.
Wanting to have children, Jeff and his wife Megan had to decide if they really wanted to know.
Along with Dr Ed Wild from the UCL Institute of Neurology, Jeff is a co-founder of HDBuzz, a website covering
The film depicts not only Jeff’s story, but his five brothers and sisters also, all of whom have undergone testing and been delivered the news by Jeff’s boss Dr Michael Hayden. Jeff describes working with Dr Hayden as “something that should be strange, but really it is wonderful. Michael is so driven that it ended up being that he motivated me, rather than the other way around. One never had to question his commitment to HD, and that made it a great place to work”.
The HD gene was discovered in 1993 and for the first time potential carriers could find out for definite if they were predisposed to developing the disease. Dr John Roder, a cancer specialist at
John’s family had a history of the disease and his father went into long term care in his early forties. John maintains that “being a scientist you always want to know what the answer is”.
Both of John’s children, now in their thirties, have recently made the decision to get tested.
The year 1988 saw the first pioneering study into the testing for
So what does the future hold for those with the HD gene? Although no one can be sure of what the future will bring, a likely scenario is that at least some of the clinical trials now in progress or being planned will result in treatments for HD patients.
Dr Wild says: “Since the abnormal gene was discovered 20 years ago, scientists around the world have been working hard to figure out how it harms the brain. That research has generated really promising leads which we hope will be tested in patients within the next two to three years. There are lots of therapies being worked on, of which the most exciting is gene silencing - giving drugs to 'switch off’ the harmful gene”.
Gene silencing, also known as huntingtin silencing, is an area of research that generates a lot of excitement. The cause of Huntington's disease is the protein huntingtin, which is made throughout the body. Huntingtin is useful, but in HD, an abnormal form of the protein called mutant huntingtin causes damage, kills neurons and eventually produces the symptoms of the disease.
The instruction set for making the huntingtin protein - the huntingtin gene - is stored in every cell and is made of DNA. To make a protein, the cell first manufactures a working copy of DNA, from a related molecule called RNA. That 'message molecule' is then read many times by the protein-making equipment of the cell, which churns out lots of copies of the protein.
This RNA message molecule is the target of gene silencing drugs. The drugs are made from chemicals similar to RNA, and are designed to stick to the huntingtin message molecule but not to other message molecules. Once stuck, the drug tells the cell's own machinery to dispose of the message molecule, so the protein isn't made.
There are different options for exactly what the drug molecules are made from, and several teams across the world are developing and testing different approaches.
So far, gene silencing drugs have been tested in several different animal models of HD, successfully delaying symptom onset or even reversing symptoms. Researchers are now racing to hone their drugs and begin human trials.
‘Do You Really Want to Know?’ is directed by Oscar-winning director John Zaritsky. It has already won awards at film festivals around the world including ‘Best Director’ and ‘Best Documentary’ at the Yorkton Film Festival and ‘Best Documentary’ at the Okanagan Film Festival.
The Open City Docs Fest is 20–23 June 2013 at UCL, Torrington Square WC1 with ‘Do You Really Want to Know?’ screened on Thursday 20 June at 6.45pm.
The film will follow with a panel discussion, panel members include Dr Jeff Carroll, Professor Sarah Tabrizi, Charles Sabine (NBC News Correspondent and HD family member), Bill Crowder (Head of Care Services for the HD Association) and Dr Elisabeth Rosser (Consultant Clinical Geneticist, Great Ormond Street Hospital).
To read more and book tickets visit the Open City Docs Fest website.
