Medicine and Health Sciences Commons^™

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

A Potential Role Of Urinary P75ecd As A Biomarker For Amyotrophic Lateral Sclerosis In An American Cohort, Swati Dhasmana, Anupam Dhasmana, Sheema Khan, Acharan S. Narula, Murali Yallapu, Subhash Chauhan

Research Symposium

Background: Neurological disorders present a unique complexity compared to other diseases, involving multiple risk factors, causes, treatments, and outcomes. These disorders often exhibit various molecular and morphological changes indicative of disruptions in cellular plasticity and resilience. The pathogenesis of many neurological disorders remains unclear, necessitating ongoing investigations. Amyotrophic lateral sclerosis (ALS) exemplifies an idiopathic and fatal neurodegenerative disease marked by the degeneration of upper and lower motor neurons. The average life expectancy post-diagnosis is a mere 36 months, primarily attributed to respiratory muscle denervation.The persistent challenges in ALS clinical trials and the absence of effective therapeutic options have intensified interest …

Ephrinb2 Knockdown In Cervical Spinal Cord Preserves Diaphragm Innervation In A Mutant Sod1 Mouse Model Of Als, Mark W. Urban, Brittany A. Charsar, Nicolette M. Heinsinger, Shashirekha S. Markandaiah, Lindsay Sprimont, Wei Zhou, Eric V. Brown, Nathan T. Henderson, Samantha J. Thomas, Biswarup Ghosh, Rachel E. Cain, Davide Trotti, Piera Pasinelli, Megan C. Wright, Matthew B. Dalva, Angelo C. Lepore

Farber Institute for Neuroscience Staff Papers and Presentations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93A mice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Advances In Molecular Pathology, Diagnosis, And Treatment Of Amyotrophic Lateral Sclerosis., Hristelina Ilieva, Mithila Vullaganti, Justin Kwan

Farber Institute for Neuroscience Faculty Papers

Although the past two decades have produced exciting discoveries in the genetics and pathology of amyotrophic lateral sclerosis (ALS), progress in developing an effective therapy remains slow. This review summarizes the critical discoveries and outlines the advances in disease characterization, diagnosis, imaging, and biomarkers, along with the current status of approaches to ALS care and treatment. Additional knowledge of the factors driving disease progression and heterogeneity will hopefully soon transform the care for patients with ALS into an individualized, multi-prong approach able to prevent disease progression sufficiently to allow for a dignified life with limited disability.

Mesenchymal Stem Cell Therapy For Amyotrophic Lateral Sclerosis, Vrushank Shah, Usmaan Al-Shehab, Keyur Patel, Alexander King

Rowan-Virtua Research Day

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a fatal neurodegenerative disease affecting motor neurons in the brain and spinal cord. Progressive muscle weakness, atrophy, and spasticity characterize the condition, which eventually leads to paralysis and respiratory failure. There is currently no cure for ALS, and the standard of care is supportive, with riluzole being the only approved medication that has been shown to slightly slow disease progression (1).

However, the use of mesenchymal stem cells (MSCs) in the treatment of ALS is a new area of research in regenerative medicine. MSCs are multipotent stem cells that …

Occupational Therapy’S Role In Addressing Sexuality And Intimacy For Individuals With Progressive Neuromuscular Disorders, Lindsay N. Richards

Student Capstone Papers

Individuals with progressive neuromuscular disorders (PND); specifically, Parkinson’s disease (PD), Multiple Sclerosis (MS), Huntington’s Disease (HD), and Amyotrophic Lateral Sclerosis (ALS) often face physical, psychological, and social challenges related to sex and intimacy. Occupational therapy (OT) practitioners are experts in activity analysis and are equipped with unique knowledge of performance skills and client factors to address deficits in occupational performance.

Though there is literature presenting the effects of PND on sexual occupations, a gap exists as it relates to qualitative data from the perspective of the individual and their partners. A mixed-methods survey was conducted examining the lived experience of …

Current Trials And Therapies For The Treatment Of Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Adam Smith, Angela Chu, Lucy Wagala, Hannah Stewart, Lindsey Peters

Pharmacy and Wellness Review

An area of health care that provides many more questions than answers includes neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, and frontotemporal dementia (FTD) are both diseases about which we know very little. However, ALS and FTD affect nearly 30,000 and 60,000 Americans respectively. Currently, there is not a cure for ALS or FTD and treatment options are aimed toward symptom management. Much of the pathophysiology of these diseases is unknown, but we do know there are genetic implications, specifically in SOD1, TARDBP and c90RF72. These mutations lead to cognitive deficits, muscle weakness and, eventually, …

Amyotrophic Lateral Sclerosis, Anastasia M. Georgetson

Student Publications

The word amyotrophic is derived from Greek, and means “without nourishment to muscles”, lateral means to the sides and sclerosis means hardened (“What is ALS?,” n.d.). First described by Jean-Martin Charcot in the 1800s, Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative motor neuron disease. Motor neurons are very important cells, and extremely unique since they can be very long with some motor neurons having a length of over a meter (“Disease Mechanisms,” n.d.).

About 5-10% of the cases of ALS are inherited, which is known as familial ALS or fALS, and it is known as autosomal dominant in these …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

The Effects Of Speech Impairment On Quality Of Life Over Time In Patients With Amyotrophic Lateral Sclerosis, Jacqueline Kelley Blessinger

PCOM Psychology Dissertations

Limited research exists on how speech impairments affect quality of life (QOL) factors over time in patients with amyotrophic lateral sclerosis (ALS). A review of the literature, including the history, disease course, and prevalence of ALS, is presented. Physical and psychosocial functioning, especially the decline of bulbar functioning’s potential impact on QOL factors and communication style, are outlined. This study is a follow-up study on a study by Duff, who found a significant difference in QOL relative to level of bulbar functioning in a cross-sectional design. The current study used a longitudinal design to look at bulbar functioning, specifically levels …

Phenotype Of Transgenic Mice Carrying A Very Low Copy Number Of The Mutant Human G93a Superoxide Dismutase-1 Gene Associated With Amyotrophic Lateral Sclerosis, Jeffrey S. Deitch, Guillermo M. Alexander, Andrew Bensinger, Steven Yang, Juliann T. Jiang, Terry D. Heiman-Patterson

PCOM Scholarly Papers

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor neuron. While most cases of ALS are sporadic, 10% are familial (FALS) with 20% of FALS caused by a mutation in the gene that codes for the enzyme Cu/Zn superoxide dismutase (SOD1). There is variability in sporadic ALS as well as FALS where even within the same family some siblings with the same mutation do not manifest disease. A transgenic (Tg) mouse model of FALS containing 25 copies of the mutant human SOD1 gene demonstrates motor neuron pathology and progressive weakness similar to ALS patients, leading to death …