Huntington’s Disease – A High-Tech Solution?

Huntington’s disease is a genetic disorder that causes the progressive death of brain’s nerve cells. This gradually results in to the loss of functional abilities and ultimately causes severe movement and cognitive impairments. The disease often strikes during a person’s prime working years and to date, there is no known cure. However, new developments in gene therapy may provide a long-awaited treatment for Huntington’s disease.

Case study: an experimental drug trial for Huntington’s disease: a future cure in sight?

To this end, an experimental drug based on the principle of gene used to treat Huntington’s disease has recently been tested on patients in London. Since the discovery of the gene responsible for Huntington’s disease in 1993, this could potentially represent a key milestone in the long-standing battle against this devastating neurodegenerative disease.

The exciting discovery here is that this drug, named ISIS-HTTRx, goes straight for the primary cause of the disease – a protein called mutant huntingtin that is caused by a genetic defect in brain cells, whereby there is an expansion of CAG (cytosine-adenine-guanine) triple repeats in the gene coding for the Huntingtin protein.

The administration of this drug is carried out at the base of the patients’ spine, directly into the cerebrospinal fluid (the fluid surrounding the brain and spinal cord). From there, the drug then migrates to the brain. In patients with Huntington’s disease, the faulty gene produces messenger RNA molecules which causes mutant huntingtin protein to be generated in the brain.

The drug has been engineered to be able to bind to these messenger molecules, and this forces the cells to dispose of the RNA molecules rather than produce the toxic mutant huntingtin protein. More importantly, it is pertinent to note that this treatment (known as an “antisense” drug) could theoretically prevent and/or reverse the effects of the toxic protein.

The human trial described herein aims to test the safety of the drug in patients who are in the early stages of Huntington’s disease by investigating if increasing the dosage of ISIS-HTTRx leads to any adverse effect. Moreover, the level of mutant huntingtin protein in the cerebrospinal fluid would also be measured to determine if the drug was achieving the effect of reducing its level. At the same time, though, it is also important to realize in the later phases of testing in humans, further assessments would still be carried out to ascertain the effectiveness of the drug.

Currently, research using mouse models of Huntington’s disease has shown much promise. These mice exhibit Huntington’s disease-like symptoms similar to those in patients, and help to facilitate investigations into the pathogenesis of the disease. Notably, when the ISI-HTTRx was administered to these “Huntington’s” mice, there were significant improvements in their Huntington’s-like symptoms with minimal severe side-effects. The next step would then be to carry the drug through to testing its efficacy and licensing it.

Concurrently, finding a solution to Huntington’s can also be complicated in the social aspect. In this regard, efforts to treat patients with Huntington’s disease by and large involve the development of drugs which would most likely be expensive.

Importantly, this would prohibit the poor communities who participate in the research studies, such as for those in South America, from being able to reap the downstream benefits of the research conducted. Even if cost was not a problem, the lack of local access of medical care and infrastructure to deliver the drugs would be major factors which prevent the treatment from getting to these people. This remains a pressing issue and is an increasingly important area of concern to healthcare professionals and policymakers alike.

New technologies to treat Huntington’s: gene silencing versus gene editing

Consider this: if we edited the DNA of patients with Huntington’s disease and removed the mutation causing all these problems, wouldn’t that cure this disease? Of course, this is all easier said than done – but advances in genome editing technologies in recent years have made what once seemed like an impossible task much closer to reality.

The nifty method to carry out genome editing is known as the CRISPR-Cas9 system. The inspiration for this technology came from the system used by bacteria naturally to protect themselves against viral infections. To put it simply, the technology consists of a synthetic guide RNA and Cas9 protein. Cas9 is an endonuclease enzyme that can cut DNA. The guide RNA is designed to match the target, and this RNA then guides the enzyme to the target DNA (or more recently RNA as well). Cas9 then uses two “molecular scissors” to carry out editing of the specific DNA of interest, which can serve a multitude of purposes.

Some potential gene editing applications to treat Huntington’s disease could include cutting out some of the extra copies of the CAG repeats which cause the disease. If the editing tool could be used to snip out part of the mutant Huntingtin gene, this would lead to it not being translated into the toxic mutant Huntingtin protein. Furthermore, the combination of stem cell and gene therapy could open up a plethora of possibilities in both the treatment of Huntington’s disease as well as many other neurodegenerative disorders. Researchers hope that this can be the first step in bringing hope to patients with such diseases that one day their conditions could potentially be cured with the development of novel treatment methods.


Abudayyeh, O., Gootenberg, J., Konermann, S., Joung, J., Slaymaker, I., Cox, D., Shmakov, S., Makarova, K., Semenova, E., Minakhin, L., Severinov, K., Regev, A., Lander, E., Koonin, E., & Zhang, F. (2016). C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector Science DOI: 10.1126/science.aaf5573

Leavitt, B., Tabrizi, S., Kordasiewicz, H., Landwehrmeyer, B., Henry, S., et al. (2016). Discovery and Early Clinical Development of ISIS-HTTRx, the First HTT-Lowering Drug to Be Tested in Patients with Huntington’s Disease. Neurology. 86:16 Supplement PL01.002.

Pouladi MA, Morton AJ, & Hayden MR (2013). Choosing an animal model for the study of Huntington’s disease. Nature reviews. Neuroscience, 14 (10), 708-21 PMID: 24052178

Sun YM, Zhang YB, & Wu ZY (2016). Huntington’s Disease: Relationship Between Phenotype and Genotype. Molecular neurobiology PMID: 26742514

Image via PublicDomainPictures / Pixabay.

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. He worked at several leading academic institutions around the globe (Cambridge University (UK), University of New South Wales (Australia), National Institute of Genetics (Japan). Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing (Scientific Biomedical Consulting Services).
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