- Results from a first human trial of an experimental drug designed to combat Huntington's disease indicated that the drug was safe and well-tolerated by the patients
- The drug, IONIS-HTTRx works by reducing the deadly huntingtin protein produced by mutated forms of the Huntington gene
- Reducing the mutated protein huntingtin stems the harmful effect on the brain and nervous system
- The novel therapy is now slotted to be a potential curative for this disease which has had no cure so far.
The first drug whose mechanism involved targeting the
corrupted gene in Huntington's disease proved to be safe and well-tolerated in
its first human trial led by scientists from the University College, London.
What is Huntington's Disease?Huntington's Disease (HD) is a fatal, progressive, neurodegenerative genetic disorder caused by the destruction of neurons in the brain. It is caused by a mutation in the HTT gene which encodes for the protein huntingtin. The HTT mutation involves a DNA segment known as a CAG trinucleotide repeat. In the normal gene, the CAG segment involves 10-35 repeats whereas in people with Huntington's the gene has around 36-120 repeats. People with more than 40 repeats usually develop the disorder. HD can occur as juvenile or adult-onset forms. The disease affects movement, cognition and emotion and symptoms include clumsy gait, difficulty in walking and performing fine motor actions, cognitive decline and emotional issues. In the juvenile and adult forms, people usually live around 15-20 years after they develop the disease with steady degeneration of functions.
HD's inheritance pattern is autosomal dominant which means one copy of the mutated gene is enough to cause the disorder. Affected individuals usually inherit the gene from one parent.
First targeted drug therapy for Huntington's diseaseAfter ten years in pre-clinical development, the first human trials for Huntington's disease began in 2015. The trial was led by Prof. Sarah Tabrizi from the University College, London Institute of Neurology. The trial was sponsored by Ionis Pharmaceuticals. Results from the trial indicated that the drug was safe and well-tolerated by the patients. The trial recruited 46 patients with early-stage Huntington disease at nine centers in the United Kingdom, Germany and Canada.
Patients received four doses of the drug, IONIS-HTTRx or a placebo. The drug was administered via injection into the spinal fluid to reach the brain. As the trial progressed, the dosage was increased according to the clinical trial design. An independent safety committee monitored patient safety at every stage.
The drug, IONIS-HTTRx is a chemically modified single strand of DNA which targets the erroneous message encoded by the mutated HTT gene. It destroys the molecule called messenger RNA which carries instruction for encoding the huntingtin protein. IONIS-HTTRx is an antisense oligonucleotide (ASO) specifically designed to break down the mutated huntingtin messenger RNA. Destroying the messenger RNA also prevents the huntingtin protein from being produced. The investigators noted that even small amounts of ASO suppressed the mutant huntingtin messenger RNA. Reducing the mutated protein huntingtin stems the harmful effect on the brain and nervous system. According to Prof. Sarah Tabrizi, Global Chief Investigator; the trial is a groundbreaking move in the treatment of HD. The novel therapy is now slotted to be a potential curative for this disease which has had no cure so far.
The study now needs further trials to generate more data on the efficacy of ASO in mitigating the devastating neurological effects of HD.
- Ground-Breaking Drug Lowers Deadly Huntington's Disease Protein For The First Time - (http://www.uclhospitals.brc.nihr.ac.uk/news/ground-breaking-drug-lowers-deadly-huntington%E2%80%99s-disease-protein-first-time)
- Drug Lowers Deadly Huntington's Disease Protein - (http://www.ucl.ac.uk/news/news-articles/1217/111217-huntingtons-disease-protein)
- Huntington Disease - (https://ghr.nlm.nih.gov/condition/huntington-disease - inheritance)
- What Is Huntington's Disease? - (http://hdsa.org/what-is-hd/)
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