Tackling Neurodegenrative Diseases with Divergent Perspectives

by Rahul Jayaram, '21

There exist numerous neurodegenerative diseases with no known cure. Current treatments of diseases such as ALS, Huntington’s disease, and Parkinson’s disease focus of suppressing symptoms rather than addressing the disease at its source. However, two new technological advancements present hope for the treatment of these types of diseases. Specifically, Brain Computer Interfaces and Antisense Oligonucleotides are each unique methods of combating neurodegenerative diseases.

​Brain computer interfaces connect one’s central nervous system to an external device, usually a computer, which creates an output based on the input of one’s brain activity. The applications for this technology are limitless. For instance, the creation of robotic arms or exoskeletons that allow for voluntary movement in patients with impaired motor function can be accomplished by detections and translation of motor cortex signals. In addition, bionic eyes can help those with visual impairment perceive the world around them by stimulating the visual cortex in response to visual input taken from a camera. [1] Scientists at the Feinberg School of Medicine are even in the process of developing a brain machine interface that can help those with ALS regain control of vocal and speaking ability. [2] By facilitation neural communication, Brain Computer Interfaces provide a wide range of services that can improve the quality of life in others. Rather than focusing on improving one’s condition internally, these machines supplement one’s function. However, this technology, which seems like nothing short of something from a Black Mirror episode, may inspire uneasiness in some people. Having your actions, perception, and, essentially, your free will determined by an external entity raises many safety and ethical questions. What happens if the interface glitches? What if this technology, along with one’s volition, falls into the wrong hands?

example pathway of neuroprosthetic arm

In contrast to the mechanical and device based treatment offered by BCI’s, innovative drug based treatments offer solutions by preventing neurological diseases at the molecular level.  Antisense Oligonucleotides are being used to reduce levels of the lethal HHT protein responsible for Huntington’s disease. Currently, there are a few treatment options, yet no cure for the disease. However, a promising therapeutic currently being studied is the use of Antisense Oligonucleotides, or ASOs. To envision how these molecules work, it is important to understand the basics of how DNA leads to protein transcription. Essentially, your DNA serves as a template for the creation of a single stranded mRNA molecules. This mRNA molecule sequence then acts as blueprint for the creation of a certain protein. ASOs are lab-engineering single stranded molecules containing a sequence complementary to a specific mRNA strand that work by binding mRNA  to form a double-stranded complex. Since protein can only be made from single stranded mRNA, ASOs inhibit the production of protein related to the gene being targeted. [3] In the case of Huntington's disease, ASOs have shown to significantly decrease HHT protein levels during clinical trials, proving to be a promising treatment for neurodegenerative disorders. ​​[4]

source: BMG Labtech

The advent of ASOs and Brain Computer interfaces stands testament to the extent to which biotechnology has advanced in the present day and illustrates how new methods are being developed to treat diseases previously considered incurable. However, there are several drawbacks to each method. As mentioned previously, Brain Computer Interfaces raise numerous concerns about the efficacy and morality of placing one’s perception in control of  a computer. In addition, these machines are costly, and initially would only be a viable treatment to the affluent. Since ASOs are a chemically based treatment administered as a drug, after clinical trials and approval, they would be easy to distribute on a large scale unlike Brain Computer Interfaces. However, a drawback of ASOs is that they are specific to a certain disease, and many trials and experiments must be conducted before this treatment matches the versatility of Brain Computer Interfaces.

In the coming years, we can expect there to be significant overlap of these treatment methods. BCIs may be able to help those undergoing ASOs therapy regain mobility and restore motor function. While we are far from perfecting these treatments, it would not be surprising to hear discussion of BCIs and ASOs appear in medical literature. Certainly, there are benefits and drawbacks to both of these treatment methods, but we must remember that we are still in the early stages of research and, if managed properly, both ASOs and BCI can change the way neurodegenerative diseases are perceived. Rather than treating the symptom, these methods can enable the disease itself to be removed.

References:
1. Podalakuru P , Sumanth BS , Selvam BP. A Breif Study Of Brain Computer Interface Advantages & Its Disadvantages. 25 February 2017.
2. Anne Feurtes R. New Brain Machine Interface could give power of speech to ALS patients. Edgy Labs. 03 October 2018.
3. Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nature Reviews Drug Discovery volume11, pages125–140 (2012). Published: 20 January 2012
4. Rinaldi C, Wood MJA. Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nature Reviews Neurology volume14, pages9–21 (2018). Published: 01 December 2011.