Date of Award

Spring 6-14-2025

Document Type

Undergraduate Honors Thesis

Degree Name

B.S. in Biological Sciences

Organizational Unit

College of Natural Science and Mathematics, Biological Sciences, Knoebel Institute for Healthy Aging

First Advisor

Daniel A. Linseman

Second Advisor

Yan Qin

Third Advisor

Casey Barker

Copyright Statement / License for Reuse

All Rights Reserved
All Rights Reserved.

Keywords

Fasudil, Amyotrophic Lateral Sclerosis (ALS), Rho-associated protein kinase (ROCK) inhibitor, Open-label, Neurofilament light chain (NfL), Glial-fibrillary acidic protein (GFAP), Ubiquitin c-terminal hydrolase L1 (UCHL1), Tau, Single molecular array (Simoa)

Abstract

The treatment of Amyotrophic Lateral Sclerosis (ALS) is an infamous problem: the disease progresses rapidly with a devastating pathogenesis. Unfortunately, there is no known cure for the condition. Despite this, several therapeutic drugs have been ingeniously designed to minimize patient suffering and extend survival. The therapeutic drug which was studied and evaluated here is a Rho-associated protein kinase (ROCK) inhibitor called Fasudil. This study design is a replicate of a recent study (P.A. van Eijk et al. 2025), but with a higher treatment dose of 240 mg/day. The sample population was treated with this dose for 24 weeks, and samples of blood serum were obtained from the population before treatment (B0), and after 12 and 24 weeks of treatment (WK12 and WK24). Four biomarkers (neurofilament light chain (NfL), glial-fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCHL1), and Tau) were measured using Single Molecular Array (Simoa™) technology for each patient, at each point of sample collection. The biomarker concentrations (pg/mL) were processed into patient and cohort means and run through a one-way ANOVA and (conditionally) paired t-tests. The results demonstrated that there was no statistically significant change in the mean serum levels of NfL or GFAP, but that there was a significant increase in mean serum UCHL1 levels and a significant decrease in mean serum Tau levels. These data suggest that high dose Fasudil was largely ineffective at altering biomarkers associated with ALS disease progression; however, the interpretation of the data is hindered by the use of an open-label study design with no placebo control group.

Copyright Date

5-24-2025

Publication Statement

Copyright is held by the author. This work may only be accessed by members of the University of Denver community. The work is provided by permission of the author for individual research purposes only and may not be further copied or distributed. User is responsible for all copyright compliance.

Rights Holder

Alexis Hoy

Provenance

Received from author

File Format

application/pdf

Language

English (eng)

Extent

36 pgs

File Size

1.3 MB

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