Fatal Huntington's disease already begins in childhood

International team of researchers gains insight into early progression and new treatment options

Although the symptoms of the fatal Huntington’s disease typically begin at the age or 30 or even later, the mutant gene which causes the disease already starts to have an effect in childhood. This is the conclusion reached by research carried out by scientists from FAU and the Universities of Cardiff and Lund. In their studies, researchers also proved that it may be possible to treat the disease with medication during this early stage.

Huntington’s disease, like Alzheimer’s and Parkinson’s, is a neurodegenerative disease, in other words, a disease which leads to the progressive dying of nerve cells in the brain. Huntington’s disease is the only one where the cause is known, namely a mutant gene inherited from one of the parents which causes an important protein molecule, the Huntingtin protein, to change into a toxic form, known as the ‘mutant Huntingtin protein’, which accumulates over time in the patient’s brain.

This leads to certain groups of brain cells needed for muscle coordination and basic mental functions slowly starting to die. As a result, patients suffer from movement disorders, show changes in their behaviour and lose their cognitive abilities. Although Huntington’s disease can be diagnosed by genetic testing before the onset of these serious symptoms, the first signs of the disease do not usually start to become apparent until between the ages of 30 and 50. Over a period of 20 years, Huntington’s disease leads to patients requiring care and attention around the clock, and always ends fatally.

‘No cure has yet been found for this purely genetic form of a neurodegenerative disease,’ according to the senior author Prof. Dr. Stephan von Hörsten, Professor for Experimental Biomedicine at FAU, who is leading the study. ‘It is therefore important for us to understand what happens in the brain of carriers of the Huntingtin gene over the entire course of their life, especially in order to be able to start effective treatment as early as possible.’ Very little is known, in particular, about the influence of the gene in infants and children. This was why the international team of scientists wanted to find out how the mutation influences the brain during this developmental phase and whether the influence of the mutant Huntingtin protein could be diminished already at this stage in time.

‘We looked at models of Huntington’s disease in the early stages of life to see whether the gene was already causing changes in the brain, affecting behaviour and the creation of new nerves as a result;’ explained the expert in molecular medicine and lead author of the study, Dr. Florian Siebzehnrübl from Cardiff University.

The results confirm what the scientists suspected: the models showed that the Huntingtin gene already affects brain development in childhood, and that this can be stopped using medicine which modulates the ‘translation’ of the genetic code into protein molecules. ‘The next step is to investigate whether this observation also applies to patients who carry the Huntingtin gene but have not yet become seriously ill,’ says Professor von Hörsten. ‘This would allow us to test in future whether possible treatments could be started at an earlier age in order to delay or even completely prevent the onset of the fatal disease.’

The study was published in the Proceedings of the National Academy of Sciences (doi. 10.1073/pnas.1807962115).

Contact for the press:

Prof. Dr. Stephan von Hörsten
Phone: +49 9131 8523504
stephan.v.hoersten@uk-erlangen.de