Every year, Huntington’s disease develops in several thousand people. It starts with mood swings and depression, later control of movements is lost, then dementia develops; late stages of paralysis. There is no medication for this disease, and its pathogenesis is still too little known: for example, the function of a protein whose mutation in the gene causes the development of the disease has not yet been established. The disease usually manifests itself at the age of 30-45 years. Patients with Huntington’s disease are forced to live for years, knowing what will be the end; the disease is covered in mass culture, for example, in the series “Doctor House.”
In the mutant gene HTT repeatedly multiplied to d it (triplet nucleotides) CAG in the HTT gene; this codon is repeated many times in the non-mutated form of the gene; the disease develops when the number of repetitions exceeds 36. As a result of the expression of the mutant gene, instead of the normal Huntingtin Htt protein it synthesizes its toxic form mHtt.
The new drug Ionis-HTTRx , which was tested by Sarah Tabrizi and her colleagues from the Huntington’s Center for the Study of Huntington’s University College London, is a signaling molecule that interferes with the synthesis of the mutant protein on the ribosome. The drug is delivered by epidural injection.
In the first phase of the clinical study, 46 men and women from the UK, Germany and Canada participated with Huntington’s disease in the early stages of development. Three quarters of the volunteers received four injections of the drug at monthly intervals; the rest received a placebo. Immediately after the first injection, the concentration of mHtt in the cerebrospinal fluid dropped sharply. The more the dose was, the more noticeable was the drop in the concentration of toxic protein. The latter fact gives grounds to believe that the production of mHtt fell due to the action of the drug. No side effects were observed.
The number of patients participating in the study was too small to make final conclusions and go to the second phase, so the Swiss pharmacological company Roche, which is sponsoring the development, plans to launch a new, more ambitious study. Tabrizi hopes that it will pass as successfully as the first. “If the drug works as we think, Huntington’s disease can be treated even before the first symptoms appear; at best, patients will need a three to four-month course of treatment, and the disease will be defeated, “she says.
About the results of the clinical study tells The Guardian, the article is being prepared for publication in the peer-reviewed journal in 2018.