Don't Hush Hush Huntington's

To understand this devastating disease, I listened to This Podcast Will Kill You's episode, Huntington's Disease: Let's talk frankly. The podcast explores being diagnosed, the biology of the disease, and its history. It expanded my knowledge of the physiology of Huntington's and the stigmas surrounding the disorder. I have always loved podcasts, but This Podcast Will Kill You is one of my favorites. I was thrilled to find an episode relevant to a neurodegenerative disorder I am studying.

This podcast starts by sharing the experience of a person who was recently diagnosed with Huntington's disease. She shares the burden of knowing there was a chance she could carry the gene, the responsibility of the decision to get tested, and the burden of knowing she was positive and sharing that information with the people in her life while battling the stigma and exclusion that might follow. These ethical questions urge me to try to think, what would I do and why?

Next, the podcast dives into the biology surrounding how this disease progresses. The podcast goes into great detail, but here are the basics...

• Our genes have strings of nucleotides that code for specific amino acids, which string together to make proteins. The nucleotides are sequences of the letters ATCG. 
• Some parts of our chromosomes contain large repeating patterns of nucleotides called microsatellites. 
• A mutation causing a trinucleotide repeat of (CAG) on chromosome 4 (AKA the huntingtin's gene) increases the length of this microsatellite, creating an abnormally shaped protein. 
• Typically the Huntingtin's gene's microsatellite has 5-28 repeats; in individuals with Huntington's disease, the mutated gene creates more than 36 repeats.
• Research shows that the more repeats there are, the earlier the onset of symptoms.
• Huntington's is an autosomal dominant neurodegenerative genetic disorder. This means it only requires one copy of the mutated gene to cause the disease. 
• Usually, this is hereditary- if one parent has the mutated gene, their kids will have a 50/50 chance of getting it. 
• In 8% of cases, this happens randomly, most likely due to increased repetitions in the parent but not at the amount required to get the disease. 
• While we don't know what precisely the normal Huntington's protein does in the body, we know it is crucial for development (without it, mice died in-utero).
• We also know that the abnormal protein leads to neuronal cell death.

For more in-depth information on this, listen to the podcast. It is complex, and we know a lot about it, but we still have a long way to go. When someone gets Huntington's, they experience varying symptoms. The early stages are marked by cell death in the brain's striatum of the basal ganglia. This region is responsible for movement coordination, mainly through muscle inhibition. So people can experience a lack of control and coordination. Many people diagnosed experience chorea or muscle twitches. Chorea begins with more distal extremities in the early stages but expands to include all muscles in later ones. People with Huntington's also experience cognitive and psychiatric change, including anxiety, depression, and decline in executive function, which can lead to changes in behavior. These behavioral changes can occur subtly long before motor symptoms appear. 

The most interesting part of this podcast dives into the history of Huntington's disease, giving insight as to why there is so much stigma around getting diagnosed. One of the first written documentation of the condition was in 1808, back when it was called the Saint Vitus's Dance or Saint Vitus's Chorea (greek for dance). Saint Vitus's Dance described all movement disorders back in the day, but the jerky movements of those affected characterized it. Although descriptions were published as early as the 1840s distinguishing what would be known as Huntington's disease from other movement disorders, it was officially renamed after George Huntington's incredibly accurate description in 1872. By the end of the 1800s, the study of genetics was becoming hugely popular, and the eugenics movement began. 

If you have never heard about eugenics, it is a movement that started in the 1800s following Mendel's studies and publications on genetics and inheritance. Eugenicists believed that selective breeding could improve humans by maintaining desirable traits and removing undesirable ones. These ideals inspired widespread sterilization of individuals with these traits seen as undesirable, including those with Huntington's disease. Many of these people were immigrants or people in minority groups. Before WWII in Germany, 400,000 people were sterilized, and 3,500 were people with Huntington's disease. The Eugenics movement also published research stating the condition was most prevalent in poor communities, further extending the scientific racism associated with the disease. False data led to the widespread prejudice, exclusion, stigmatization, and shame of those diagnosed well into the 1950s, 60s, and even as late as the 1980s. 

When the marker for Huntington's disease was founded in 1983 and the specific gene in 1993, the stigmas began to decline as ethical dilemmas and debate rose. The ethics of getting genetically tested took the forefront in the conversation about Huntington's, and doctors and clients battled with the decision and the impacts it could have on the patient's privacy of others in their family. 

Everyone has the right to decide whether they want to know, but one family member knowing often takes away that right for another, which is why this is such a complex decision. It is also why I will never be able to imagine what it is like to make that decision myself. You can imagine how you would react, but the only people who know are the ones facing it themselves. However they go about, this decision needs to be respected and upheld, especially by medical professionals. 

It is not all sad news; there are some breakthrough treatment possibilities in the works that could drastically change the realities of people with Huntington's. I have included some articles outlining those breakthroughs below. Several organizations are tirelessly working to reduce the stigma people with Huntington's face daily, and they are working towards spreading awareness and facilitating open communication. Listening to stories like the ones in this podcast is essential to destigmatizing this diagnosis. 

Eugenics and scientific racism. Genome.gov. (n.d.). Retrieved August 3, 2022, from https://www.genome.gov/about-genomics/fact-sheets/Eugenics-and-Scientific-Racism 

Exactly Right. (2021, May 23). This Podcast Will Kill You/Huntington’s disease: Let’s talk frankly. This Podcast Will Kill You. episode. 

Full stack genome engineering. Synthego. (n.d.). Retrieved August 3, 2022, from https://www.synthego.com/blog/crispr-in-huntingtons-disease#the-genetics-of-huntingtons-disease 

Gardner, J. (2021, May 27). UNIQURE moves Huntington's gene therapy to next phase of key trial. BioPharma Dive. Retrieved August 3, 2022, from https://www.biopharmadive.com/news/uniqure-huntington-gene-therapy-high-dose/600940/