Post #3: Investigating Neurofilaments and Their Role in Identifying MS Disease Progression

Recently, a research journal entitled “Neurofilaments as Biomarkers in Neurological Disorders” published in Nature Reviews Neurology earlier this year by Michael Khalil et al. investigated neurofilaments and their role in identifying MS in patients. Included in this study was the purpose of neurofilaments, how neurofilament light chains can be used as a biomarker to identify disease progression in MS patients, and how the techniques can be used to help in the identification of effective treatments for MS and other neurological disorders.

To begin, neurofilaments, a part of the neurons, are thought to be important components in providing radial growth and overall stability in axons throughout the body. Therefore, when MS causes disease progression and axonal injuries, these neurofilaments are released into the body. Certain techniques using four different generations of immunoassays (a biochemical test that can help identify these neurofilaments) can identify the levels of these neurofilaments in both the cerebral spinal fluid (CSF) and the blood. If this is done, the concentration of these neurofilaments can be an important indicator in determining the level of disease progression for MS. The first two generations of immunoassays work for identification in CSF, although identification in blood is only reliable in the third and fourth generation immunoassays identified in the study (these immunoassays are more sensitive).

This process is an important landmark in not only identifying how severe a patient has MS, but it can also be an effective tool in future MS research. This process can be used in future clinical trials to help determine how well a MS treatment works by comparing the number of neurofilaments that are in the blood before and after treatment. This process is also much more reliable than using MRI scans which are only reliable in showing damage in white matter, while MS causes damage in both white matter and gray matter. While the first and second generation immunoassays have limitations based on low sensitivity (and therefore rely on CSF sampling), the newer third and fourth generation immunoassays have opened up opportunities in future testing and research. While not perfect, these immunoassays could help find a future treatment, if not a future cure, for MS.

As said before, the information in the above paragraphs was located in an article published in Nature Reviews Neurology entitled “Neurofilaments as Biomarkers in Neurological Disorders” by Michael Khalil et al.. The link to the article is listed below.

https://www.nature.com/articles/s41582-018-0058-z#Sec5

Post #2: Converting Astrocytes into Myelinating Cells In Vivo for Possible MS Treatment

Multiple sclerosis, or MS, is a disease that is characterized by the degradation of the myelin sheaths in the central nervous system (CNS). As one of the autoimmune diseases that our group has chosen to focus on, this autoimmune disease results in the interruption of nerve signals in the body, creating many cognitive and physical impairments upon the individual affected. This disease currently is very difficult to combat, and many patients lose a lot of their function over the course of many years. A recent study done by Maryam Ghasemi-Kasman, Leila Zare, Hossein Baharvand, and Mohammad Javan explored the ability to convert astrocytes within the CNS into oligodendroglia in vivo in order to combat the myelin destruction associated with this disease.

According to the study, when the degradation of myelin occurs, astrocytes appear in higher numbers at the injury site. These astrocytes change the inflammatory response in the body, creating a situation where the myelin cannot repair itself and therefore helps in the progression of nerve damage. The study completed by the four researchers above found that forcing the expression of the miR-302/367 cluster in astrocytes can create a situation where the astrocytes will turn into oligodendroglia, or nerve cells that naturally repair the myelin within the CNS. This study was completed using mice subjects, and after the above process was completed the study found an increase in neurological function within the mice and saw increased myelination via staining techniques. This conclusion shows a possibility for remyelination within the human body, which eventually could lead to the slowing if not the reversal of MS and other neurogenerative diseases.

The above information was found on the SCOPUS database. This study was published in the Journal of Tissue Engineering and Regenerative Medicine in 2018. The DOI for the scientific journal is below.

10.1002/term.2276

Brooke Smiley: Autoimmune Disease Introduction Post

Autoimmune diseases, or diseases in which a person’s own immune system attacks their body’s cells, are a prevalent form of disease in the world today. Every year, there are many people worldwide that are diagnosed with autoimmune diseases, and each disease varies greatly. Not only does each disease attack a different bodily organ, but  each one can also range in severity from mildly noticeable to severely debilitating. Some diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA), can end up creating much hardship on the patient in terms of life quality and length as well as financial difficulties for repeated hospital visits and treatments. Therefore, many researchers worldwide are trying to find the cause of these diseases in order to prevent, treat, and hopefully even cure these diseases. Researchers are trying to find ways to use scientific, engineering, and biological principles in order to achieve these ends.

My group for EN1 is investigating some of these autoimmune diseases and how the field of biomedical engineering is progressing towards the outcomes outlined in the above paragraph. For me, I want to investigate this topic further because I feel that autoimmune diseases, especially ones like MS and RA, can be extremely detrimental to the lives of those who suffer from them. I want to learn about the current research on the topic to find out what the possibilities are in terms of treatments or possible cures in the future related to the field of biomedical engineering.

Therefore, I took the first steps in my path of research by obtaining an article written by Hugh McDevitt from the Department of Microbiology and Immunology and Department of Medicine at the Stanford University School of Medicine. Called “Specific Antigen Vaccination to Treat Autoimmune Disease” (published on October 5 of 2004), it is one of the first articles that extrapolated upon research into T cells to find a possible cause of autoimmune disease and the use of vaccines containing antigens to treat the T cell problems by altering certain mechanisms within the body. Having been cited many times since then, this article expresses many of the founding principles of the research done for autoimmune diseases and how vaccines were first shown to have some effects in mice for treating the problems associated with autoimmune diseases and T cells. While the article expresses that many of the symptoms were prevented, stopped, or reversed in many of the mice to which the vaccines were given, the article also expressed danger in the use of these vaccines. In the studies cited in the article, many mice formed hypersensitivity to the vaccine, creating a problem where repeated doses of the vaccine would cause anaphylaxis to the point where death resulted for a majority of the mice. While human tests for similar vaccines only created small local reactions, the severe outcome of the various mice studies creates a need for further studies to be completed before any vaccine research and findings become viable.

Overall, I need to investigate further this broad outlook of the use of vaccines and other treatments to help the T cell issues present in autoimmune diseases. I will likely look at some of the more recently written articles that cited this early piece. However I also want to investigate other modes of treatment and study, as I feel that T cells, while important to this topic, may only be one key to engineering a treatment or cure for these diseases.

The links below are to the resources I used to begin the above research. The first link is to the National Institute of Allergy and Infectious Diseases website where I located the basic information for the description of autoimmune diseases, while the second link is to the article published by Hugh McDevitt.

https://www.niaid.nih.gov/diseases-conditions/autoimmune-diseases

https://doi.org/10.1073/pnas.0405235101