While any genetic disorder is devastating to those affected and their families, almost none are more so than neurodegenerative disorders like Huntington’s Disease. Huntington’s Disease is one of the most destructive disorders out there. It’s rare, affecting only about 7 out of 100,000 people, but it is dominantly linked, meaning a person only needs to inherit one copy of the mutated gene from a parent to have a 50% chance of developing Huntington’s. It is characterized by loss of motor control, such as involuntary movement, and difficulty speaking and swallowing. Additionally, mental symptoms like sudden and gradual mood changes, memory loss, and brain fog affect patients. All of this culminates in neurodegeneration so severe that it becomes terminal. Until recently, it has been a death sentence from the moment of diagnosis.
Huntington’s is caused by a mutation of the HTT gene, aptly named huntingtin. The disorder occurs when an individual has an extended repetition of the CAG sequence within the gene. In non-affected people, CAG repeats between 6-35 times. In Huntington’s individuals, it can repeat 40+ times. This mutated gene causes HTT protein to become toxic to the human body. In order to function properly, proteins in the body fold to become 3D. During this folding process, mutated HTT genes will misfold and disrupt gene transcription (creation), thus spreading the disease. Ultimately, the diseased neurons will die, which results in the loss of motor control and cognitive decline that we see in patients diagnosed with Huntington’s.
Released on September 24, the University College London (UCL) revealed the results of a six-year-long study where 17 patients out of 29 total were given a dose of AMT-130, which is a virus that codes a small segment of RNA to target the creation of proteins whose folding, when mutated by the CAD gene repetition, causes Huntington’s Disease and facilitates its progression. The patients given the dose were compared to a control group of Huntington’s-affected individuals who were given a placebo.
The results were astounding. Over a period of three years, patients given the dose slowed the progression of the disease by a staggering 75%. While the treatment has changed the lives of the patients involved in the trial, the study was very small by scientific standards. In order to increase the validity of the results and gain FDA approval, more trials will need to be conducted, and they will need to produce similar or better results. However, if AMT-130 does pass those additional trials and gain approval, it would become the first drug to actually stop the progression of Huntington’s in one dose, rather than just managing the symptoms.
