This research study is being done to learn if RO7814278 is safe and can help people with Huntington’s disease (HD). HD can be passed down from parents to their children through their genes. People with HD have too many sets for creating a particular combination of C, A, and G, called a CAG repeat, and have a gene that does not work properly because of this. It makes huntingtin protein that is not normal and doesn’t work the way it’s supposed to (and therefore it’s called mutant huntingtin protein). Over time, this mutant huntingtin protein builds up and causes the symptoms of Huntington’s disease. People with HD have both normal and mutant huntingtin protein in their body.

RO7814278 is an experimental drug transmitted by an adeno-associated virus (AAV). It is a gene therapy that delivers  genetic instructions to create a specific microRNA into the brain cells to reduce huntingtin RNA and protein in a nonallele-specific manner. This means that cells treated with RO7814278 will have reduced levels of both normal and mutant huntingtin protein (mHTT) mRNA and protein. In HD, the mutant huntingtin protein (mHTT) cause brain atrophy and clinical symptoms affecting motor function, cognition, and behavior. The goal of RO7814278 is to have it work in the body for a very long time after a single dose and help reduce the amount of mutant huntingtin protein (mHTT) in the brain. This may stop or delay the worsening of HD. It could also have no effect at all.

This study is the first time RO7814278 will be tested in humans, but it has been given to animals.  Part A is the dose escalation part of the study. Dose escalation is when the study team starts by giving a small dose of study treatment to a small group of participants. If that dose doesn’t cause any major side effects for those participants, the researchers will increase the dose for another small group of participants. Each study participant will receive only a single dose of RO7814278 at a single-dose level. The goal of dose escalation is to find the best dose of a study treatment for participants to receive. Once Part A of the study is complete, the data monitoring committee will look at the data and decide if the study should proceed.