Juvenile Huntingtons Disease: The Terrific Types of Therapy

 

     Hello, my wonderful geeks and nerds, and welcome back to another science-packed post! This week, we will be delving into a continuation of last week's scientific encounter. As you may recall we previously spoke about Juvenile Huntington's Disease (JHD), its causes, symptoms, etc. However this week we are diving even deeper to explore the therapy methods for this disease. So, without further ado, let's begin!

    To start with a brief recap, JHD is a genetic disorder in juveniles caused by abnormal CAG repeats in the Huntingtin gene with over 60 repeats. To understand that jargon I suggest you take a look at last week's blog. However, this disease is fascinating in the way that the cause of it is completely understood yet the treatment for it is... iffy. That is due to several factors such as ethics issues with experimental testing on juveniles, lack of funding or research, and overall complexity of the brain disease. Yet despite these issues, certain treatments have been considered for this disease after being tested on animal models and certain adult subjects. To understand these potential treatments we must go through each individually.

    Gene therapy: This form of therapy works by specifically targeting the DNA for the mHTT gene. By doing so the issue is hit at the root cause before the mRNA can transcribe the DNA. Once within the nervous system, the gene has three different ways to combat the production of the mHTT from the core. The first is replacing in which the administered gene replaces the corrupted gene. The second is gene silencing in which the corrupted gene is blocked from being produced. The third is adding a gene to fight against the mHTT without directly replacing it or blocking it. However, this method does not come without its disadvantages. These are costly and dangerous operations that, for the most part, have only been proven to be effective in animal testing. Furthermore, while gene therapy is used in several neurodegenerative diseases there is still limited research on its effect on Huntington's disease, and has not been tested for Juvenile Huntington's disease quite yet. Nonetheless, this is an effective therapy method and by applying it to JHD a new and effective treatment for this disease may be uncovered. This is delivered through injection (Tabrizi, n.d.).

    Small molecule: This therapy uses low molecular weight compounds (under 900 daltons) to easily and efficiently combat disease. These molecules work well due to their simple structure which makes it easy for them to transverse the BBB. They function by blocking, mimicking, or boosting the activity of biological components such as enzymes, receptors, or proteins. This is directly related to HD because small molecules can boost protective agents such as BDNF that can reduce the damage made by the mutant Huntington protein. This therapy is administered in the form of drugs such as tablets, capsules, or soft gels. This therapy method works on fixing the issues associated with the disease rather than fixingthe disease itself (What Are Small Molecule Drugs?, 2024).

Biologics: This therapy involves making medication using living organisms. Scientists do this by using cells to create medication in specialized facilities which is used to combat disease within the body. The cells used in this process help the medication grow and thrive in order to be used in the biological system. Afterward, the medication is isolated away from the cells and injected into the body. Unlike small molecule therapy, biologics have to do with complex structures that do not navigate throughout the BBB as easily. This is correlated to HD because these cells can be used to bind to the mHTT by creating antibodies to combat the antigen. Furthermore, these cells can also work on de-escalating the damage made by the mHTT by lowering inflammation. This therapy method is done through injection. It works on both targeting the disease itself and the issues created by the disease. However, it is complicated, costly, and difficult to maintain (Biologics (Biologic Medication & Drugs): What It Is & Types, 2024).

    Cell therapy: This process is done by directly using the cells within the patient to create the medication. First, the cells are taken out of the patient and then brought in a lab to modify and eventually add back to the body to combat disease within it. Cell therapy can be used to reduce brain inflammation, regenerate neurons, and reverse neuronal damage. Furthermore, it targets the genetic cause (i.e. mHTT) to deconstruct it and can help fight against it by fixing issues caused by the mutation such as damaged brain tissue by regenerating it. This therapy method targets the main cause by remedying issues caused by it. Yet this is another form of therapy that is costly and not thoroughly researched (Shah et al., n.d.). 

    Protein therapy: In this therapy, a protein is injected to combat the disease. This is done in five different ways. The first is the replacement of a protein that is defective and unstable. The next is adding to an existing pathway which combats the disease. The third is interfering with a harmful molecule of the organism. The fourth is adding a function that can help the body attack the disease, and the last is delivering helpful proteins that can help remedy issues with the disease. In the case of HD protein therapy can be used for multiple causes from blocking the mHTT to increasing the amount of a helpful pathway such as BDNF to help remedy the issue. However, while this treatment has a diverse amount of courses for treatments it also comes with various setbacks. The most obvious is that it is costly to make these proteins and is not a simple process. Another significant issue is that this protein is immunogenicity meaning that it may be seen as foreign by the immune system and be attacked (Ghosh et al., n.d.). 

    

    Immunomodulatory Therapy: In this therapy, a chemical agent is used to modify the functioning of the immune system. This therapy is correlated to HD as HD has to do with a severe amount of inflammation. By using this therapy this issue can be reduced significantly which aids in preventing the progression of the disease. While this issue is primarily caused by the mHTT gene, cell degeneration also plays a significant role in the growth of this gene. Yet this therapy method only combats the symptoms but not the root cause of the disease. However, currently, this therapy is entirely experimental and is not reliable enough to be used as a genuine method (Tripathy & Tsui, 2024).

    That's all for today folks! Thank you for reading and to end this off a question: what therapy do you find to be the most effective? Anyway, I hope you learned something new and I will see you next week!