Hope for Huntington's disease

Affecting around 8,500 UK people currently, with an additional 25,000 set to be affected as they age, Huntington ’s disease is a grave diagnosis. Those with the condition will experience gradual deterioration of bodily and mental functions such as movement, thinking, understanding and behaviour until they are unable to look after themselves, and eventually die. Clearly, it is a devastating prognosis for those directly affected and their family and friends. However, will a new experimental treatment finally put an end to this deadly condition? (1, 2)

What is Huntington’s disease?

Huntington ’s disease (HD) is a neurodegenerative condition, which means it involves the destruction of cells in the central nervous system. In HD, the cells destroyed are in the brain, and since the brain controls the body’s processes, this means the body deteriorates in several ways as the disease progresses. (2)

Usually, the first symptom that a person with HD will experience is changes in behaviour. They may appear to lack empathy, experience great fluctuations in mood, struggle to concentrate and lack interest in activities, work, social situations and personal hygiene. (3)

Movement problems also appear early on in the disease, beginning as occasional twitching of the face and jerking of the arms and legs. Eating and drinking will also become a challenge as the muscles of the mouth and throat lose function. This will become more pronounced and happen more often as time goes on, but eventually, stiffness of the muscles may take over. (3)

Other symptoms implicated in HD include depression, suicidal thoughts, poor communication including slurred speech and difficulty verbalising ideas, and sexual problems ranging from reduced sex drive to lewd behaviour. (3)

In the final stages of the disease, people with HD will need round-the-clock care. The most common cause of death at this point is infection, primarily pneumonia. Life expectancy after diagnosis is between ten and 25 years. (2, 3)

What is the cause?

HD is an inherited genetic disease, so it is passed down from parent to child in DNA (genetic material) at the point of conception. Our DNA is split into 23 pairs of chromosomes, all containing genes (sequences of DNA that act as a ‘code’ for proteins, the building blocks of the body). On each chromosome in pair number 4 is located a gene that codes for a protein called huntingtin, essential for the structure of the brain’s nerve cells. It is a faulty version of this gene that produces a toxic form of huntingtin that instead kills cells in the basal ganglia and cortex regions of the brain, leading to HD. This faulty gene is a dominant allele, which means you only need one copy of the gene within the pair to develop HD. Any children of a person with one safe copy and one faulty copy of the gene have a 50% chance of inheriting the disease themselves. In the very rare instance that the parent has two faulty copies, all of their children will go on to develop HD. (4, 5)

Treatment: the promising news

Up until now, the only treatment for HD was supportive, helping to ease the symptoms rather than preventing progression or curing the condition. Such treatments include antidepressants and antipsychotics. But on 11th December 2017, the news broke that a drug trialled at University College London had been successful in reducing the levels of the toxic huntingtin protein in the brain, and the licence has been bought by the pharmaceutical company Roche to take up larger trials, then hopefully production and supply. This is groundbreaking in the field of neurodegenerative disease, as it is believed that similar drugs may be able to be developed for other conditions involving toxic proteins such as Alzheimer’s disease and Parkinson’s disease. (1, 2, 6)

In the trial, the experimental drug was injected into the cerebrospinal fluid of patients with HD each month for four months. Of the 46 patients, approximately 12 were administered a placebo (an injection containing no drug). Samples of cerebrospinal fluid were taken after each dose, and the levels of corrupt huntingtin were lower each time in patients given the drug. (6)

The drug works by inactivating the messenger RNA (another type of genetic material similar to DNA) which translates the ‘codes’ in the genes into the toxic huntingtin protein. (1, 6)

It is hoped that if the drug makes it to mainstream use, it could be given at regular intervals to people with the faulty gene before symptoms appear, meaning their brain will be protected from the devastating effects of toxic huntingtin and they will be able to live a life free of HD. (6)

For further help and support, visit the Huntington’s Disease Association’s website here.

Picture: pixaboy.com

References

1. Gallagher J (2017). ‘Huntington’s breakthrough may stop disease’, BBC News. Available at: http://www.bbc.co.uk/news/health-42308341

2. NHS Choices. Overview [cited 11 December 2017]. Available at: https://www.nhs.uk/conditions/huntingtons-disease/

3. NHS Choices. Symptoms [cited 11 December 2017]. Available at: https://www.nhs.uk/conditions/huntingtons-disease/symptoms/

4. Huntington’s Disease Association. What causes Huntington’s disease? [cited 11 December 2017]. Available at: https://www.hda.org.uk/huntingtons-disease/what-is-huntingtons-disease/what-causes-huntingtons-disease

5. NHS Choices. Causes [cited 11 December 2017]. Available at: https://www.nhs.uk/conditions/huntingdons-disease/causes/

6. Devlin H (2017). ‘Excitement as trial shows Huntington’s drug could slow progress of disease’, The Guardian. Available at: https://www.theguardian.com/science/2017/dec/11/excitement-as-huntingtons-drug-shown-to-slow-progress-of-devastating-disease

   Author: Gabby Gallagher MPharm

   Medically reviewed by: Superintendent pharmacist Margaret Hudson BSc(Hons)MRPharmS 14/12/17