Pharmacy and Pharmaceutical Sciences Commons^™

Incidence And Severity Of Drug Interactions Before And After Switching Antiretroviral Therapy To Bictegravir/Emtricitabine/Tenofovir Alafenamide In Treatment-Experienced Patients., Jason J. Schafer, Pharmd, Mph, Bcps, Aahivp, Neha S Pandit, Agnes Cha, Emily Huesgen, Melissa Badowski, Elizabeth M Sherman, Jennifer Cocohoba, Ayako Shimada, Scott W Keith

College of Pharmacy Faculty Papers

Background: Switching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug-drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

Methods: This was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool's HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients' preswitch ART regimens with their CM list. The …

Apixaban Discontinuation For Invasive Or Major Surgical Procedures (Adios): A Prospective Cohort Study., Geno J. Merli, Walter K. Kraft, Luis H. Eraso, Taki Galanis, Lynda J. Thomson, Geoffrey O. Ouma, Eugene Viscusi, Jerald Z. Gong, Edwin Lam

Department of Medicine Faculty Papers

Background

Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care peri-operative management.

Methods

This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician.

Results

One hundred and …

Assessing Pharmacy Student Knowledge, Intent To Practice, And Perceptions Of Current Learning As It Pertains To Pharmacist Furnishing Of Hormonal Contraception In Pennsylvania, Ashley Sargent, Bs, Nicasia D'Allesandro, Bs, Danielle Mayer, Pharmd, Bcacp

College of Pharmacy Posters

Objectives:

1. Assess student pharmacist knowledge of pharmacist prescribing of hormonal contraceptives and important details in order to safely and effectively prescribe
2. Assess student pharmacist attitudes and intention of offering this service if Pennsylvania allows for this innovative role
3. Assess student perceptions of curricular education to provide direct pharmacy access to hormonal contraception

1-Chromonyl-5-Imidazolylpentadienone Demonstrates Anti-Cancer Action Against Tnbc And Exhibits Synergism With Paclitaxel, Karan Modi, Scott Lawson, Guanglin Chen, Deepthi Tumuluri, Inga Rekhtman, Michael Kurtz, G Cristina Brailoiu, Qiao-Hong Chen, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Curcumin has been well studied for its anti-oxidant, anti-inflammatory, and anti-cancer action. Its potential as a therapy is limited due to its low bioavailability and rapid metabolism. To overcome these challenges, investigators are developing curcumin analogs, nanoparticle formulations, and combining curcumin with other compounds or dietary components. In the present study, we used a 1-chromonyl-5-imidazolylpentadienone named KY-20-22 that contains both the pharmacophore of curcumin and 1,4 benzopyrone (chromone) moiety typical for flavonoids, and also included specific moieties to enhance the bioavailability. When we tested the in vitro effect of KY-20-22 in triple-negative breast cancer (TNBC) cell lines, we found that …

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation For Cancer Therapy, Ankit K. Rochani, Sivakumar Balasubramanian, Aswathy Ravindran Girija, Toru Maekawa, Gagan Kaushal, Phd, D Sakthi Kumar

College of Pharmacy Faculty Papers

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is …

Lc-Ms Based Stability-Indicating Method For Studying The Degradation Of Lonidamine Under Physical And Chemical Stress Conditions, Ankit K. Rochani, Margaret A. Wheatley, Brian Oeffinger, John R. Eisenbrey, Gagan Kaushal

College of Pharmacy Faculty Papers

Background and purpose: Lonidamine is a hexokinase II inhibitor, works as an anticancer molecule, and is extensively explored in clinical trials. Limited information prevails about the stability-indicating methods which could determine the forced degradation of lonidamine under stressed conditions. Hence, we report the use of a rapid, sensitive, reproducible, and highly accurate liquid chromatography and mass spectrometry method to analyze lonidamine degradation. Experimental approach: The Xbridge BEH shield reverse phase C18 column (2.5 μm, 4.6 × 75 mm) using isocratic 50:50 water: acetonitrile with 0.1% formic acid can detect lonidamine with help of mass spectrometer in tandem with an ultraviolet …

Apc-Β-Catenin-Tcf Signaling Silences The Intestinal Guanylin-Gucy2c Tumor Suppressor Axis., Erik S Blomain, Jeffrey A Rappaport, Amanda M Pattison, Babar Bashir, Ellen Caparosa, Jonathan Stem, Adam E Snook, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Sporadic colorectal cancer initiates with mutations in APC or its degradation target β-catenin, producing TCF-dependent nuclear transcription driving tumorigenesis. The intestinal epithelial receptor, GUCY2C, with its canonical paracrine hormone guanylin, regulates homeostatic signaling along the crypt-surface axis opposing tumorigenesis. Here, we reveal that expression of the guanylin hormone, but not the GUCY2C receptor, is lost at the earliest stages of transformation in APC-dependent tumors in humans and mice. Hormone loss, which silences GUCY2C signaling, reflects transcriptional repression mediated by mutant APC-β-catenin-TCF programs in the nucleus. These studies support a pathophysiological model of intestinal tumorigenesis in which mutant APC-β-catenin-TCF transcriptional regulation …

What’S The Word? Defining Community Pharmacy Interventions, Elizabeth Laughlin, Bsps, Danielle C. Mayer, Pharmd, Bcacp, Sarah Lynch, Pharmd, Bcacp

College of Pharmacy Posters

Primary Objective: Determine whether student pharmacists & licensed pharmacists are consistently able to categorize interventions

Secondary Objective: Evaluate trends in themes for situations that are not easily categorized

Discrepancies In Written Versus Calculated Durations In Opioid Prescriptions: Pre-Post Study., Benjamin H. Slovis, John Kairys, Bracken Babula, Melanie Girondo, Cara Martino, Lindsey M. Roke, Jeffrey Riggio

Department of Medicine Faculty Papers

BACKGROUND: The United States is in the midst of an opioid epidemic. Long-term use of opioid medications is associated with an increased risk of dependence. The US Centers for Disease Control and Prevention makes specific recommendations regarding opioid prescribing, including that prescription quantities should not exceed the intended duration of treatment.

OBJECTIVE: The purpose of this study was to determine if opioid prescription quantities written at our institution exceed intended duration of treatment and whether enhancements to our electronic health record system improved any discrepancies.

METHODS: We examined the opioid prescriptions written at our institution for a 22-month period. We …

The Incidence And Severity Of Drug Interactions Before And After Switching Antiretroviral Therapy To Bictegravir/Emtricitabine/Tenofovir Alafenamide In Treatment Experienced Patients, Ciara Walshe, Pharmd Candidate, Jason J. Schafer, Pharmd, Mph, Bcps-Aq Id, Bcidp, Aahivp

College of Pharmacy Posters

Objective

• The primary outcome was to measure the proportion of patients experiencing DIs before and after the ART switch.
• The secondary outcome was to measure changes in DI scores before and after the ART switch.

Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both …

Flavonoids And Other Polyphenols Act As Epigenetic Modifiers In Breast Cancer., Priyanga Selvakumar, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid's anti-cancer action in breast cancer. The dose is another key …

Unexpected Cell Type-Dependent Effects Of Autophagy On Polyglutamine Aggregation Revealed By Natural Genetic Variation In C. Elegans., J Alexander-Floyd, S Haroon, M Ying, A A Entezari, C Jaeger, M Vermulst, T Gidalevitz

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Monogenic protein aggregation diseases, in addition to cell selectivity, exhibit clinical variation in the age of onset and progression, driven in part by inter-individual genetic variation. While natural genetic variants may pinpoint plastic networks amenable to intervention, the mechanisms by which they impact individual susceptibility to proteotoxicity are still largely unknown.

RESULTS: We have previously shown that natural variation modifies polyglutamine (polyQ) aggregation phenotypes in C. elegans muscle cells. Here, we find that a genomic locus from C. elegans wild isolate DR1350 causes two genetically separable aggregation phenotypes, without changing the basal activity of muscle proteostasis pathways known to …

Autocatalytic Tissue Polymerization Reaction Mechanism In Colorectal Cancer Development And Growth., Bruce M Boman, Arthur Guetter, Ryan M Boman, Olaf A Runquist

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of our study was to measure the kinetics of human colorectal cancer (CRC) development in order to identify aberrant mechanisms in tissue dynamics and processes that contribute to colon tumorigenesis. The kinetics of tumor development were investigated using age-at-tumor diagnosis (adenomas and CRCs) of familial adenomatous coli (FAP) patients and sporadic CRC patients. Plots of age-at-tumor diagnosis data as a function of age showed a distinct sigmoidal-shaped curve that is characteristic of an autocatalytic reaction. Consequently, we performed logistics function analysis and found an excellent fit (p < 0.05) of the logistic equation to the curves for age-at-tumor diagnoses. These findings indicate that the tissue mechanism that becomes altered in CRC development and growth involves an autocatalytic reaction. We conjecture that colonic epithelium normally functions as a polymer of cells which dynamically maintains itself in a steady state through an autocatalytic polymerization mechanism. Further, in FAP and sporadic CRC patients, mutation in the adenomatous polyposis coli (APC) gene increases autocatalytic tissue polymerization and induces tumor …

Expression Of Tryptophan 2,3-Dioxygenase In Metastatic Uveal Melanoma, Mizue Terai, Eric R Londin, Ankit Rochani, Emma Link, Bao Lam, Gagan Kaushal, Alok Bhushan, Marlana Orloff, Takami Sato

Kimmel Cancer Center Faculty Papers

Uveal melanoma (UM) is the most common primary eye malignancy in adults and up to 50% of patients subsequently develop systemic metastasis. Metastatic uveal melanoma (MUM) is highly resistant to immunotherapy. One of the mechanisms for resistance would be the immune-suppressive tumor microenvironment. Here, we have investigated the role of tryptophan 2,3-dioxygenase (TDO) in UM. Both TDO and indoleamine 2,3-dioxygenase (IDO) catalyze tryptophan and produce kynurenine, which could cause inhibition of T cell immune responses. We first studied the expression of TDO on tumor tissue specimens obtained from UM hepatic metastasis. High expression of TDO protein was confirmed in all …

Impact Of In-House Specialty Pharmacy On Access To Novel Androgen Axis Inhibitors In Men With Advanced Prostate Cancer, Anna Driscoll, Nathan Handley, Md, Mba, Adam Binder, Siobhan Henry, W. Kevin Kelly, Do

Phase 1

Introduction: Novel androgen axis inhibitors are standard of care treatments in advanced prostate cancer. The billed amounts for these medications are often very high, which may create significant financial toxicity for patients and lead to delays in treatment. Our institution implemented an in-house specialty pharmacy in 2014, that provides these medications and evaluates copay assistance options for all patients. We evaluated the program’s impact on out of pocket cost (OOP) and turnaround time (TAT).

Methods: We reviewed available internal specialty pharmacy records to identify prescriptions for abiraterone or enzalutamide filled between 1/1/17 and 12/31/18. Payments were stratified by primary payment …

Using Electrolyte Repletion Guidelines To Improve The Rate Of Oral Potassium And Magnesium Delivery, Joshua Riley, Alan Kubey, Md

Phase 1

Introduction: Evidence-based guidelines for electrolyte replacement that safely encourage oral (PO) and/or intravenous (IV) dosing more successfully attain goal levels than standard care. However, the Thomas Jefferson University Hospital (TJUH) electrolyte replacement guidelines (JG 11-1296), approved in 2002 and last updated in 2008, provide guidance for IV repletion not PO. Between 5/2017-11/2017, TJUH dosed potassium and magnesium in a 2.30 and 4.24 IV:PO ratio, respectively. If 50% of doses were given PO, we anticipate ~$800,000 annual TJUH savings.

Methods: We created a multidisciplinary team and completed a literature review to inform the creation of updated TJUH guidelines for …

Non-Traditional Anti-Emetic Therapy For Cannabinoid Hyperemesis Syndrome: A Case Report, Sara Groome, Pharmd, Kelly Le, Pharmd, Christina Karalis, Pharmd, Eric Selvage, Pharmd, Brandi Thoma, Pharmd, Bcps, Bccp

Pharmacy Presentations, Posters, and Grand Rounds

• Marijuana is one of the most commonly utilized recreational drugs and is widely known for both its anti-emetic and appetite-stimulating properties
• Medicinal-grade marijuana has been available for patients suffering from various medical conditions, such as chemotherapy-induced nausea and vomiting, for example; it also has been utilized in patients with chronic pain, in addition to a number of other disease states
• While casual, intermittent use elucidates the aforementioned positive effects, chronic use of large quantities of marijuana may precipitate the contrary, such as extensive nausea and vomiting, a hallmark of Cannabinoid Hyperemesis Syndrome (CHS)
• CHS is hypothesized to result from alterations …

A Real World Assessment Of The Efficacy And Safety Of Switching From Tdf To Taf In Treatment Experienced Patients With Hiv Infection, Jaclyn O'Connor, Pharmd Candidate, Kaitlin N. Sassa, Pharmd, Jason J. Schafer, Pharmd, Mph, Bcps Aq-Id, Bcidp, Aahivp

College of Pharmacy Posters

Objective

• The primary objective of this study was to determine if patients maintain viral suppression after switching from TDF to TAF
• The secondary objective was to assess changes in renal function and serum cholesterol levels

Clinical Interventions Documented By Appe Students: Results From A Pilot Study, Elizabeth Laughlin, Bsps, Danielle Mayer, Pharmd, Bcacp, Sarah Lynch, Pharmd, Bcacp

College of Pharmacy Posters

Primary Objective: Evaluate the types of drug therapy problems identified by student pharmacists and the results of these interventions.

Secondary Objective: Evaluate trends in trends of what type of interventions are identified and how they are defined.

Markers Of Bone And Lipid Metabolism With Eslicarbazepine Acetate Monotherapy., Scott Mintzer, Tawnya Constantino, Barry Gidal, Parul Bhargava, Todd Grinnell, David Blum

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the impact of eslicarbazepine acetate (ESL) monotherapy on markers of bone and lipid metabolism.

METHODS: We conducted a post-hoc analysis of data pooled from two Phase III, dose-blind, conversion-to-ESL (1600 mg and 1200 mg) monotherapy studies in patients with focal seizures. Laboratory measurements included lipids (total cholesterol [TC]; high-density lipoprotein cholesterol [HDL-C]; low-density lipoprotein cholesterol; and triglycerides) and markers of bone metabolism (alkaline phosphatase; 25-hydroxyvitamin D; osteocalcin; and parathyroid hormone [PTH]); measurements were taken at baseline, Week 18, and Month 12, and analyzed according to enzyme-inducing antiepileptic drugs (EIAEDs) use at baseline (+EIAED and -EIAED subgroups).

RESULTS: …

Connecting Health Plan Care Managers With A Network Of Enhanced Services Community Pharmacies: A Pennsylvania Case Study, Nicholas Leon, Pharmd, Stephanie Mcgrath, Pharmd, Kim Coley, Pharmd, David Pope, Pharmd, Elizabeth Grassmyer, Melissa A. Mcgivney, Pharmd, Patricia Epple

College of Pharmacy Posters

PPCN pharmacies have been able to successfully collaborate, bi-directionally, with health plan care managers to improve patient health and enable appropriate utilization of healthcare resources

To build off of our early success, additional systems and tracking capabilities are being explored related to the following:

• Bi-directional tracking of referrals
• Care managers to pharmacists
• Pharmacists to care managers
• Delivery drivers as community health workers
• Drug class specific interventions (ex. a focus on opioids)
• Disease state specific interventions (ex. a focus on asthma or type 2 diabetes)
• Formal interventions focused on dialing patients back into the services/resources offered by health plans

PPCN is …

Relationships Among Patient Diabetes Self-Care Behaviors, Depression And Self-Reported Medication Adherence In African Americans With Diabetes, Shu Xiao, Phd, Pharmd Candidate, Monica Woloshin, Bs, Pharmd Candidate, Robin Casten, Phd, Barry Rovner, Md, Ginah Nightingale, Pharmd, Bcop

College of Pharmacy Posters

Objectives

To determine the extent to which self-care behaviors and self-reported medication adherence are related to depression in older African Americans with diabetes who presented to the ED.

Changes In Body Mass Index And Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate To Tenofovir Alafenamide., Jason J. Schafer, Kaitlin N. Sassa, Jaclyn R. O'Connor, Ayako Shimada, Scott W. Keith, Joseph A. Desimone

College of Pharmacy Faculty Papers

Background: Switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF)-containing antiretroviral therapy (ART) can improve renal function and bone mineral density in people with human immunodeficiency virus (PWH). The switch can also negatively influence cholesterol, but changes in body mass index (BMI) and atherosclerotic cardiovascular disease (ASCVD) risk are unknown.

Methods: This retrospective observational study evaluated BMI and ASCVD risk score changes in virologically suppressed PWH who switched from TDF to TAF without switching other ART regimen components. Adults on TDF for ≥1 year with 2 consecutive HIV ribonucleic acid values/mL before a TAF switch were included. Body weight, …

Patients Living With Hiv Infection Are Less Likely To Receive The Correct Statin Intensity For Cardiovascular Disease Risk Reduction, Jason J. Schafer, Pharmd, Mph, Roshni Emmons, Pharmd, Bcps, Nick V. Hastain, Pharmd, Todd Miano, Pharmd, Phd

College of Pharmacy Posters

• Patients living with HIV (PLWH) are at high risk for atherosclerotic cardiovascular disease (ASCVD)
• Eligible PLWH should receive statins for ASCVD risk reduction according to current guidelines
• Studies suggest that statins are underprescribed in PLWH, but comparisons to uninfected patients and assessments of statin intensity have not occurred

Objective

To determine the influence of HIV infection on appropriate statin prescribing for ASCVD risk reduction

Exploring The Prevalence And Characteristics Associated With Weight Gain And Metabolic Changes In Plwh Who Are Virologically Suppressed On Antiretroviral Therapy And Switch To Integrase Inhibitor Containing Regimens, Matty Zimmerman, Joseph Desimone Jr., Md, Jason J. Schafer, Pharmd, Mph, Bcps-Aq Id, Bcidp, Aahivp

College of Pharmacy Posters

Objectives

• To determine the prevalence, extent and characteristics of weight gain among virologically suppressed PLWH whose ART has been switched to an INSTI-containing regimen
• To examine the presence of metabolic changes in PLWH who have been switched to INSTI-containing ART

Pharmacokinetics Of Intraperitoneal Vancomycin In Patients On Automated Peritoneal Dialysis, Edwin Lam, Yi Ting Kayla Lien, Valvanera Vozmediano, Stephan Schmidt, Walter K. Kraft, Jingjing Zhang

Department of Pharmacology and Experimental Therapeutics Posters

Primary Objective

• Characterize the pharmacokinetics of vancomycin in plasma, dialysate, and urine following a single intraperitoneal dose

Secondary Objective

• Explore the safety, tolerability, and feasibility in administering vancomycin during the long dwell period in patients on APD

No Meaningful Drug Interactions With Doravirine, Lamivudine And Tenofovir Disoproxil Fumarate Co-Administration., Matt S. Anderson, Jocelyn Gilmartin, Li Fan, Ka Lai Yee, Walter K. Kraft, Ilias Triantafyllou, Christina Reitmann, Ying Guo, Rachael Liu, Marian Iwamoto

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Doravirine (DOR) is a novel non-nucleoside reverse transcriptase inhibitor available as a single tablet and a three-drug combination with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) to treat HIV-1 infection. These analyses assessed pharmacokinetic (PK) interactions with co-administration.

METHODS: Two trials were conducted. Study 1: two-period, fixed-sequence; 8 healthy participants; Period 1, DOR 100 mg followed by ≥7-day washout; Period 2, TDF 300 mg once daily for 18 days, co-administration of DOR 100 mg on day 14. Study 2: three-period, crossover, 15 healthy participants; Treatment A, DOR 100 mg; Treatment B, 3TC 300 mg + TDF 300 mg; Treatment …

Codelivery Of Genistein And Mirna-29b To A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates., Koita Sacko, Karthik Thangavel, Sunday A. Shoyele

College of Pharmacy Faculty Papers

This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated …

Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …