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ALS is a rapidly progressive, fatal disorder caused by motor neuron degeneration, for which there is a great unmet therapeutic need. AMX0035, a combination of sodium phenylbutyrate (PB) and taurursodiol (TUDCA, TURSO), has shown promising results in early ALS clinical trials, but its mechanisms of action remain to be elucidated. Therefore, our goal was to obtain an unbiased landscape of the molecular effects of AMX0035 in ALS patient-derived cells.We investigated the transcriptomic and metabolomic profiles of primary skin fibroblasts from sporadic ALS patients and healthy controls (n = 12/group) treated with PB, TUDCA, or PB-TUDCA combination (Combo). Data were evaluated with multiple approaches including differential gene expression and metabolite abundance, Gene Ontology and metabolic pathway analysis, weighted gene co-expression correlation analysis (WGCNA), and combined multiomics integrated analysis.Combo changed many more genes and metabolites than either PB or TUDCA individually. Most changes were unique to Combo and affected the expression of genes involved in nucleocytoplasmic transport, unfolded protein response, mitochondrial function, RNA metabolism, and innate immunity. WGCNA showed significant correlations between ALS gene expression modules and clinical parameters that were abolished by Combo treatment.This study is the first to explore the molecular effects of Combo in ALS patient-derived cells. It shows that Combo has a greater and distinct impact compared with the individual compounds and provides clues to drug targets and mechanisms of action, which may underlie the benefits of this investigational drug combination.

ALS is a rapidly progressive, fatal disorder caused by motor neuron degeneration, for which there is a great unmet therapeutic need. AMX0035, a combination of sodium phenylbutyrate (PB) and taurursodiol (TUDCA, Turso), has shown promising results in early ALS clinical trials, but its mechanisms of action remain to be elucidated. To obtain an unbiased landscape of AMX0035 effects we investigated the transcriptomic and metabolomic profiles of primary skin fibroblasts from sporadic ALS patients and healthy controls treated with PB, TUDCA, or PB-TUDCA combination (Combo). Combo changed many more genes and metabolites than either PB or TUDCA individually. Most changes were unique to Combo and affected the expression of genes involved in ALS-relevant pathways, such as nucleocytoplasmic transport, unfolded protein response, mitochondrial function, RNA metabolism, and innate immunity. Weighted gene coexpression network analysis showed that significant correlations between ALS gene expression modules and clinical parameters were abolished by Combo. This study is the first to explore the molecular effects of Combo in ALS patient-derived cells. It shows that Combo has a greater and distinct impact compared to the individual compounds and provides clues to drug targets and mechanisms of actions, which may underlie the benefits of this investigational drug combination.

Mason has a wealth of resources that can help your students reach your course goals, such as the library, Writing Center, Communications Center, Data Services Center, Office of Academic Integrity, Center for the Advancement of Well-being, Women and Gender Studies Center, First-Gen+ Center, LGBTQ+ Resource Center, Disability Services, Learning Support Services, Global Education Office, OSCAR, Harmonize, Blackbooard, and more. For the first 45 minutes, come hear instructors explain how they have used a range of campus resources in their courses. For the next 45 minutes, chat with representatives from various offices about how you might incorporate them into your classes. Lightning talk presenters: Jennifer Ashley (College of Humanities and Social Sciences) – will discuss DiSC classroom instruction and workshops Katie Clare (CWB)- will discuss the resources from the Center for the Advancement of Well-Being Janet Ha Poirot (CHSS-School of Integrative Studies) – will discuss Learning Services Anna Habib (English) – will discuss the Writing Center Steven Harris- Scott (History & INTO Mason) – will discuss GEO study abroad option added to World History course Susan Howard (College of Humanities and Social Sciences) – will discuss resources, including recommending individual sessions to her students, possibly recommending the ESL opt-in program to her multilingual writers, and inviting tutors to her class to give workshops. – on demand Esther Namubiru (INTO Mason) – will discuss integration of library services Bonny Paez (INTO Mason) – will discuss OAI Breakout rooms: BREAKOUT ROOM #1: First-generation and Undocumented Students at Mason Amber Holton-Thomas (First-gen+ Center) BREAKOUT ROOM #2: The Communications Lab Briana M. Stewart (Communications) BREAKOUT ROOM #3: The Writing Center and Writing Across the Curriculum Tom Polk (WAC) Courtney Massie (University Writing Center) Susan Lawrence (Writing Center)- will discuss the Writing Center This session will highlight resources for teaching and learning to write that are available to both students and faculty at Mason. With a primary focus on students at all levels, the Writing Center provides individual consultations, workshops, writing groups, and written resources, along with specialized support for multilingual and advanced graduate writers. With a primary focus on faculty and curriculum, the Writing Across the Curriculum (WAC) Program offers workshops, learning communities, and consultations to support the instruction of writing in all disciplines. The WAC Program also supports faculty writing productivity and wellness through its Faculty Writers Community programming. BREAKOUT ROOM #4: Disability Services and Assistive Technology Initiative Naomi Martinez-Jones (Disability Services) Korey Singleton (Assistive Technology Initiative) This session will highlight the resources in place to support faculty, staff, and students with disabilities in the Mason community. This includes but is not limited to common student accommodations, how to implement accommodations, inclusive design strategies, digital accessibility resources (e.g., Blackboard Ally, captioning/transcription, document remediation), and more. BREAKOUT ROOM #5: University Libraries, Digital Scholarship Center, and Discipline Librarians Alyssa Fahringer (DiSC) will describe the services and resources the Digital Scholarship Center offers Kimberly Macvaugh (University Libraries) will represent the Subject Librarians BREAKOUT ROOM #6: Learning Services Vicki Dominick (University Life) Learning Services assists students with “learning how to learn” in order to achieve their academic goals. Many students find that learning and studying at Mason is different than what they were accustomed to in high school or community college. The staff provides a variety of free services to empower students to study effectively, manage assignments, and prepare for exams. In this breakout room, we will discuss how instructors can refer students to our services, including Academic Success Workshops, individual academic coaching, online academic success videos, and the tutoring resource list. In addition, instructors will learn how to invite an Academic Coach to visit their class to talk about study strategies. BREAKOUT ROOM #7: Office of Academic Integrity LaShonda Anthony (OAI) will discuss general challenges and share approaches to embed and promote integrity in the classroom, including an examination of assessment materials. BREAKOUT ROOM #8: OSCAR Karen Lee (OSCAR) Jesse Guessford (Office of Undergraduate Education) We will discuss the resources available at OSCAR, the Office of Student Scholarship, Creative Activities, and Research that faculty can use to increase opportunities for undergraduate students to get involved in research, scholarly, or creative projects. We will also discuss other resources available through the Office of Undergraduate Education. BREAKOUT ROOM #9: Center for the Advancement of Well-Being Katie Clare (CAWB) will discuss resources from the Center for the Advancement of Well-Being to support the Mason community as we work toward Goal #7 around thriving and well-being. A university that is thriving around well-being must see this work embedded throughout the campus culture, not limited to CAWB. BREAKOUT ROOM #10: Career Services Elena Chiru (University Career Services) Rachel Lindsey (University Career Services) BREAKOUT ROOM #11: Women and Gender Studies Center Anu Aneja (Director) David Corwin (Associate Director) This session will highlight the resources in place to support faculty, staff, and students in the Women and Gender Studies Program and Center. These include but are not limited to our library, guest presentations, Intersectionality 101 training, gender-related expertise consultation, and a variety of programs your students can be involved in. BREAKOUT ROOM #12: LGBTQ+ Resources Center Josh Kinchen (Director) BREAKOUT ROOM #13: Harmonize Online Discussion, Chat & Q&A Platform Darren Wacker, Regional Sales Manager Ramelle Riley, VP of Partnerships Created in response to educator and student feedback, the Harmonize platform seamlessly integrates with learning management systems to create an engaging, collaborative community for dynamic academic discussion, creative and analytical thinking, and in-depth feedback that drives improved learning outcomes. To learn more about 42 Lines, visit 42lines.net. To learn more about Harmonize, visit harmonize.42lines.net. BREAKOUT ROOM #14: Classroom Technologies and Learning Support Services Crystal Clemons (Learning Support Services) BREAKOUT ROOM #15: Blackboard Lisa Andion, Senior Solutions Engineer Lisa Clark, Senior Client Experience Manager Zeina Habal, Regional Vice President Leslie Kent, Client Experience Manager, Innovations in Teaching & Learning Conference Proceedings, Vol. 13 (2021): Fostering Inclusive Excellence