ASOs: They’re Not Nonsense

Huntington’s Disease is a genetic disorder which causes loss of motor coordination (chorea), deterioration cognitive functions, and increase in psychiatric problems over time. These symptoms are caused by a repeat mutation in the protein Huntingtin. The mutant builds up in the brain and nerves over time, causing an array of symptoms. While we currently still researching how mutant Huntingtin causes this disease, we  do know that its presence directly harms the brain.

Currently, there is no cure for Huntington’s Disease. Physicians treat the individual symptoms in hopes of increasing the quality of life of those affected by the disease. Patient are often prescribed a cocktail of pharmaceuticals, ranging from antipsychotics to anti-chorea medications. Most of the drugs prescribed to Huntington’s patients, such as the anti-chorea medication Tetrabenazine, can unfortunately exacerbate other symptoms of the disease. Sadly, the patient is also overcome by the disease’s symptoms in time.

On October 3^rd2018, an article appeared in Science Translational Medicine, showing hope for a new method of treatment. Amber Southwell et al. found that using an antisense oligonucleotide (ASO) reduced the production of the mutant Huntingtin protein, alleviating the cognitive and psychiatric symptoms of the disease. The ASO reduces the mutant protein’s production by binding to the gene’s mRNA before it is transformed into a protein.

Amber Southwell and her team found that not only do ASOs reduce the amount of mutant Huntingtin, but the effects of ASO dosage are long lasting. The ASO which showed the most promising results was muHTT1.

The study used humanized mice, who expressed the dominant mutation Hu97/18. Hu97/18 is associated with Huntington’s Disease. At 6 weeks, the mice were given an injection of either phosphate-buffered saline (PBS) or an ASO, such as muHTT1. Mutant Huntingtin presence was quantified by western blot on protein extracted from brain samples. The samples were taken from mice at various ages to determine treatment’s longevity (figure 1).

Treatments with ASOs are giving Huntington’s Disease patients increasing hope as studies continue with non-human primates. While there is still no absolute cure to Huntington’s, there is hope for increased quality of life of those suffering.