Human Relevant Models Needed for MS Research

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Blog written by AxoSim Research Assistant Sabrina Dillon

March marks Multiple Sclerosis (MS) Awareness Month. MS is a demyelinating disease concerning the central nervous system (CNS). In 2020, approximately 2.8 million individuals were afflicted with MS globally (5). The prevalence of the disease has been on the rise since 2013, with the 2020 estimate showing a 30% increase from that in 2013 (5). The direct cause of MS is unknown (5). Similarly, there is currently no cure for the disease (5).

MS is the predominant progressive neurological disease in young adults, with the average diagnosis being at 32 years old (4) (5). With diagnosis occurring in such a productive time period of a person’s life, the socioeconomic burden is devastating (2). Further exacerbating this burden is the fact that the disease is chronic. As a result, there is reduced productivity in the workplace due to shorter schedules, early retirement and unemployment (1). Another consequence lies in family life, as this is a common time for starting a family (5).

In 2013, total MS-related costs were estimated to be $4.3 billion in the United States (1). At the patient level, the annual cost can vary with ranges beginning at $8,529 and ending at $54,244 (1). Of that cost, prescriptions are the largest contributor. Even with insurance coverage, MS patients spend the most out-of-pocket when compared to other individuals that file for bankruptcy due to medical expenses (1). The average out-of-pocket spending is approximately $36,167 at the time of declaration (3). Because of the nature of the disease, home modifications are imperative, as they functionally support patients while also preventing injuries. However, these alterations can cost anywhere from $100 to up to $50,000 (1). With these financial burdens quickly adding up, it is unfortunately common for patients to stray from their treatment plans, thus deteriorating their health.

My first research experience was in a MS lab at the Miami Project to Cure Paralysis, where I assisted Dr. Melanie Plastini in her dissertation research. She was studying the role of oligodendrocyte-specific mitochondrial dysfunction in MS onset, particularly primary progressive MS onset. While I primarily worked on her mouse model, Dr. Plastini was simultaneously conducting iPSC research using MS patient and control samples. This experience initially triggered my interest in neurodegenerative diseases. While studying for my master’s degree, I was able to further pursue these interests by taking a neurobiology of disease class, in which we learned about a number of these diseases.

It’s only fitting that I now find myself working for AxoSim, a company which has the potential to dramatically expand our understanding of MS. There is a tremendous need for human-relevant models of the disease, as the alternatives tend to fall short. AxoSim’s human BrainSim® technology has a promising future as such a model. Through our platform, we will be able to better characterize the pathology of this disease by inducing similar conditions in differentiated human iPSC cells. The BrainSim® platform comprises of neurons, astrocytes and most importantly in this disease, oligodendrocytes. This allows us to effectively mimic the in vivo environment of the MS nervous system in terms of cell interactions and histoarchitecture. As a result, we will be able to observe and analyze multiple facets of the disease to produce data that is highly translatable to patients. For instance, we will be able to study the interaction between dysfunctional oligodendrocytes and neurons throughout the demyelination process. From this, we may be able to gain insight into the etiology of the disease. This platform may also be capable of exhibiting remyelination in an MS phenotype, which would be revolutionary in terms of therapeutics.

I’m excited to see AxoSim’s future contributions to neurodegenerative disease research. I hope that we can work toward increasing the quality of life for these patients and ultimately curing MS.

Works cited

(1) Asche, Carl V. “The Financial Toxicity of Multiple Sclerosis.” Research Outreach, 3 Aug. 2021, https://doi.org/10.32907/ro-124-1542718721.

(2) Orack, Joshua C., et al. “Concise Review: Modeling Multiple Sclerosis with Stem Cell Biological Platforms: Toward Functional Validation of Cellular and Molecular Phenotypes in Inflammation-Induced Neurodegeneration.” Stem Cells Translational Medicine, vol. 4, no. 3, Mar. 2015, pp. 252–260., https://doi.org/10.5966/sctm.2014-0133.

(3) Sadigh, Gelareh. “Out of Pocket Cost Communication in Multiple Sclerosis Patients.” ClinicalTrials.gov, U.S. National Library of Medicine, 5 Feb. 2020, https://clinicaltrials.gov/ct2/show/NCT04257071.

(4) Wallin, Mitchell T., et al. “The Prevalence of MS in the United States.” Neurology, vol. 92, no. 10, 5 Mar. 2019, pp. e1029–e1040., https://doi.org/10.1212/wnl.0000000000007035.

(5) Walton, Clare, et al. “Rising Prevalence of Multiple Sclerosis Worldwide: Insights from the Atlas of MS, third edition.” Multiple Sclerosis (Houndmills, Basingstoke, England), vol. 26, no. 14, Dec. 2020, pp. 1816-1821., https://doi.org/10.1177/1352458520970841.