A new era for Huntington’s disease treatment

Scientists cured a case of Huntington's disease for the first time in history.

Huntington’s Chorea, commonly known as Huntington's disease, is caused by a mutation in the HTT gene that ordinarily provides instructions for producing the huntingtin protein.

This protein plays a crucial role in cellular transport, organelle trafficking and gene regulation, making it essential for brain development..

The brutal neurodegenerative disorder essentially strips away the autonomy of those affected, causing involuntary movements, decreasing their cognitive skills, and causing a large array of diverse mental and physical issues that parallel dementia and Parkinson’s disease. 

Huntington’s disease is primarily hereditary; only 1-3% of people who develop Huntington’s disease have no family history of the disorder. However, this doesn’t mean the trait is recessive — a child only needs to inherit one copy of the mutated gene from either parent to create it. 

The mutated version of the HTT gene affects the cytosine-adenine-guanine trinucleotide repeat (CAG) DNA segment. In an unaffected individual, the CAG segment is repeated 10-35 times within the HTT gene while people with Huntington’s disease see the segment repeated up to 120 times.

This increase in the CAG segment leads to the production of unnaturally long huntingtin proteins, which are separated into smaller, toxic fragments that bind together and disrupt the normal functions of neurons. The dysfunctional neurons cause the symptoms of Huntington's disease and eventually lead to death. 

Thanks to the efforts of Sarah Tabrizi, director of the University College London Huntington's Disease Centre, and Ed Wild, a consultant neurologist at the National Hospital for Neurology and Neurosurgery at UCLH, Huntington’s disease was successfully treated for the first time on Sept. 24.  

The new treatment aims to permanently reduce the levels of the huntingtin protein in an individual by combining gene therapy and gene silencing technologies that are applied. 

While this does not fix the gene itself, it lessens the potential symptoms. Scientists use a modified virus, called an adeno-associated virus as a delivery system, engineered to carry a piece of genetic material that makes brain cells produce microRNA. 

The microRNAs, which naturally regulate how much protein a cell makes, target the messenger RNA (mRNA) that comes from the mutated variation of the HTT gene. By binding to the mRNA, the microRNA stops the cell from producing large amounts of the toxic huntingtin protein. Ultimately, the goal is to reduce production of the damaging protein while allowing the brain’s cells to survive longer and function better.

Delivering this therapy is an intuitively delicate process.

The brain region affected by the huntingtin gene sits deep within the skull.  Surgeons have to use advanced imaging techniques to guide thin catheters directly into the caudate nucleus and putamen, the two structures in the striatum most affected by Huntington’s. 

During the 12-18-hour surgery, the adeno-associated virus is slowly infused in six parts of the brain, allowing it to spread throughout the target area. Once there, the viral vectors enter neurons and begin producing the therapeutic microRNA. The treatment is designed to be long-lasting — even potentially permanent — since neurons are not replaced over time, meaning a single infusion might provide benefits that last for years.

In the 29 patients the treatment was tested on, the disease slowed its progression by an average of roughly 75%. 

The average life expectancy after the onset of Huntington’s disease is typically 10-30 years. With this medical advancement slowing the deterioration patients could potentially have decades more to live with a better quality of life.

It is safe to say that the results of the treatment are in fact exceptional, especially considering the fact that nothing has even come close to treating Huntington’s disease to this extent. 

This is not to say that implementing this new treatment will be easy; it will most likely be expensive and unavailable to a large portion of the general population. However, the findings of the research provide hope for people with this disease if not now, then in the future. 

Beyond Huntington’s disease, the treatment could be a pathway into developing similar approaches for other neurodegenerative disorders caused by the misfolding of proteins or toxic accumulation. Conditions like Parkinson’s disease, ALS and certain forms of dementia could one day benefit from tailored gene-silencing interventions.