The ticking time bomb; Huntington’s disease

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Huntington’s disease is a rare genetic illness that occurs in about one in every 15,000 people in the UK and causes the degeneration of neurons in the brain. This results in a number of issues, such as movement based symptoms (eg. involuntary jerking and difficulty with speech), cognitive symptoms (eg. lack of impulse control and difficulty learning new information) and psychiatric symptoms (eg. insomnia and social withdrawal). 

The protein that causes these symptoms is known as the ‘Huntington protein’. This causes the abnormal expansion of a naturally occurring protein linked to axonal transport (transport of neural impulses), making it toxic and causing the neurons to die. It is also an autosomal dominant disease, meaning that it only requires one parent to have the disease to result in a 50% chance of any offspring inheriting the symptoms.

Huntington’s disease is fascinating as it is one almost exclusively defined by genetics. The average person has between 10-15 copies of the base CAG on Chromosome 4. This is linked with axonal transport and cell survival. However, once a person has 39 copies or more, they are officially labelled as having Huntington’s. To be precise, a person with 39 copies of the CAG nucleotide has a 90% chance of having dementia at age 75, and their first symptoms occurring at the age of 66. An increase in copies present results in the appearance of symptoms earlier on. At 40 copies, there is a 90% chance of first symptoms occurring at 66, with 41 copies the age of occurrence is 54, with 42 the age is 37 and with 50 the age is 27. To make it worse,  as the number of copies of CAG increases, the DNA becomes harder to read by anti-codons and other transcriptional molecules. This means that as the number of copies increases, the more mutations occur, and the greater the severity of the disease becomes, both in a single lifetime and over generations. Huntington’s disease forces a tightly bound death sentence upon its victims. After the initial onset, it takes an average of 15 years for the person to die from the disease, meaning that someone with 50 copies has a life expectancy of 42.

That being said, there are certain foods that can provide a degree of protection or harm to those already with the mutation. The protein MNAT2 (which is lost in Huntington’s) protects neurons from stress, and prevents the misfolding of other proteins. Caffeine has been found to boost the functionality of this protein, meaning that people with Huntington’s disease who drink much caffeine generally have less severe symptoms. 

On the other hand, eating a high amount of dairy products has shown a correlation with the development of Huntington’s disease. This may be due to dairy products lowering the amount of uric acid in the blood, which has been shown to increase the effect of Huntington’s. However, the researchers are not completely sure whether this correlation may be valid. It is possible that people with more severe Huntington’s require more energy than the average person for cellular processes, and as a result they therefore eat higher proportions of food with a greater calorific value – such as dairy products.

Unfortunately, there is no way to stop this disease. While Huntington’s has already been cured in mice (as early as the year 2000), it was only in 2017 that any scientific advancement occurred in curing humans. In California, a drug was created (IONIS-HTTRx ) which worked to attach itself to the messenger RNA carrying the code for the toxic protein. This prevented the mutant DNA from transcribing itself, and in a specific case it succeeded in destroying the RNA. However, this does also damage the normal protein produced by CAG repeats, as well as the mutant Huntington gene, which has been described as a ‘gamble’ (Peter Forbes). It is for this reason that there is still no official cure for Huntington’s.

To conclude, it is clear that Huntington’s is a fascinating yet horrific disease – one that can be seen as a ticking time bomb, currently without a way to stop it.


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