Huntington’s Disease (HD) is a genetic neurodegenerative disorder, characterised by progressive development of hyperkinetic movements, the involuntary actions of the limbs and torso (Roos, 2010). The progressive neurodegeneration also results in psychiatric disturbances and cognitive impairment (Walsam, et al. 2018). It is caused by an abnormality in chromosome 4; an expanded CAG repeat on the short arm, which encodes an abnormally long polyglutamine repeat (over 40 repeats), compared to the 10-36 average in healthy individuals (Ross and Tabrizi, 2011). This leads to eventual cell loss in the caudate and putamen, both neurological centres for voluntary skeletal movement and cognitive functioning (Chitnis & Karunapuzha, 2009). Other affected areas include the CA1 region of the hippocampus, cortical layers 3, 5, 6 and the centromedial-parafascicular complex of the thalamus (Rubinsztein, 1996). These neurological deficiencies will eventually begin to manifest symptomatically, within all facets of the individual’s life. No cure is currently available, meaning symptomatic progression is inevitable and the disease is always fatal. The individual’s quality of life will continuously deteriorate to the extent they can no longer provide adequate care for themselves or satisfy their basic needs without full-time care (Mueller, Petersen & Jung, 2019). Current intervention strategies, such as drug treatment, can somewhat mitigate this by managing arising symptoms, albeit with notable caveats.
Both Tetrabenazine (TBZ) and Deutetrabenazine (DBZ) have enjoyed moderate success as pharmacological interventions for Huntington’s Disease. As vesicular monoamine transporter 2 inhibitors, they reversibly deplete monoamines from nerve terminals (Chitnis & Karunapuzha, 2009), predominantly within the caudate and putamen, brain regions severely affected by (Leavitt and Hayden, 2006). This has been found to alleviate the irregular, involuntary movements of the limbs and torso (Mayo Clinic, 2020). However, as dopamine antagonists, both drugs forcibly deplete monoamines, which can often lead to people experiencing symptoms of depression and other related mood disorders (Jankovic & Beach, 1997). The treatment of the motor symptoms, therefore, comes at the expense of psychological ones, often requiring additional drug treatment with antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs). Quite often, people can end up on a long-term cocktail of pharmaceutical substances whereby something is prescribed to remove the side effect of something else. Consequently, drug treatment for the hyperkinetic symptoms of Huntington’s Disease is inadequate on its own, and arguably still in its infancy.
Alternative forms of intervention have been investigated, in order to supplement drug treatment or circumvent it entirely. Two of the most widely used alternatives are physical therapy and exercise. Physical Therapy focuses on repeating task-specific exercises, which allows the individual to practice and improve their performance on these daily physical tasks made difficult by Huntington’s Disease. In people with early-to-mid-stage Huntington’s Disease, Ciancarelli et al. (2013) found significant improvements in gait, posture and coordination, following a 3-week multidisciplinary neurorehabilitation programme, consisting of conventional neuromotor rehabilitation exercises. Improvement of independence in functional activities reliant on dexterity and fine motor skills was also found. Although this supports physical therapy as a mitigator for the motor deficiencies associated with Huntington’s Disease, the improvement observed following the programme vanished after treatment was discontinued. This suggests physical therapy may be best approached as a long-term treatment on an outpatient basis, to perpetuate improvements over a longer period of time. Furthermore, longitudinal studies examining gait and balance over a longer period may reveal issues with the design of such physical therapy programs that are difficult to detect short-term.
For instance, a two-year intensive multidisciplinary rehabilitation program with an emphasis on physical exercise found ‘non-significant improvements’ in gait and balance across all physical outcome measures (Piira et al. 2014). However, caution must be taken when interpreting these results as only 6 of the already small sample (n=10) completed the full 2-year programme). Attrition is a pervading limitation of longitudinal research. However, it is particularly prevalent when working with people with neurodegenerative disorders, as a result of Huntington’s Disease-related symptoms and cognitive impairment (Quinn et al. 2009). Furthermore, a larger sample size may have found a more significant improvement, as a result of the program. Perhaps it would be worth replicating the study with a higher initial participant count, to better control for attrition.
In addition to physical therapy research has also established the benefits that more general exercise carries for both physical and mental health. Moderate increases in energy expenditure due to physical activity have been shown to improve life expectancy and physical capabilities (Myers et al. 2004). Aerobic exercise has been linked to a higher production of dopamine and serotonin (Heijnen et al. 2015). Furthermore, some studies have found exercise to carry many benefits for aiding the treatment of depression in the wider population (Martinsen, 2012). With a lower baseline for physical and mental health, people with Huntington’s Disease may see more benefits from exercise compared to the general population. In contrast, it could be argued that those in the mid-to-late stages of Huntington’s Disease may not be able to achieve an adequate training stimulus due to cognitive or motor impairments (Mueller, Peterson & Jung, 2019). These individual differences need to be considered when conducting research and making exercise-related recommendations based on such research. However, with dopamine-antagonist medications like Tetrabenazine and Deutetrabenazine already putting some people at risk of depression, the psychological impact of exercise could produce enough of a difference to make drug treatment more pleasant for some people with Huntington’s Disease.
Author Cameron Box, MSc, MBPsS | Team Leader, Northern Healthcare
Resources and support
If you or a loved one have recently been diagnosed with Huntington’s Disease it can be difficult to process the range of emotions that you may be experiencing. There is no right or wrong way to feel, please know that you are not alone. Here are some resources and support groups that you may find helpful:
Huntington’s Disease Association branches and support groups are run by volunteers. Groups meet up and down the country for a mixture of social activities, information sessions, fundraising and awareness raising – and always a good chat. For more information about branches and support groups email [email protected] or call 0151 331 5444.
You may also find it useful to read NHS guidance on Treatment and Support for those living with Huntington Disease and their loved ones.
thebraincharity.org.uk has a range of resources on Huntington’s disease, support for families and information on many other disability-related issues.
