EXTH-91 - Galectin-3 Inhibitor Paired with Focal Low-Intensity Noninvasive tDCS Can Achieve Maximal Therapeutic Benefit in Clinically Relevant Meningioma Mouse Models

Friday, November 18, 2022

7:30 PM – 9:30 PM ET

Location: West/Central Hall

Poster Presenter(s)

Arabinda Das, Ph.D

Medical University of South Carolina
Charleston, United States

Author(s)

DM

Daniel G McDonald, MS

Medical University of South Carolina
Charleston, United States
MY

Milad Yazdani, M.D.

Medical University of South Carolina
Charleston, United States
Connor Stephenson, MHS

Medical University of South Carolina
Charleston, United States
SM

Shikhar Mehrotra, Ph.D.

Medical University of South Carolina
Charleston, United States
CW

Cynthia A. Welsh, M.D.

Medical University of South Carolina
Charleston, United States
LI

Libby Kosnik Infinger, M.D.

Medical University of South Carolina
Charleston, United States
WV

William A A. Vandergrift III, III, M.D.

Medical University of South Carolina
Charleston, United States
AV

Abhay K. K. Varma, M.D.

Medical University of South Carolina
Charleston, United States
SP

Sunil J. J. Patel, M.D.

Medical University of South Carolina
Charleston, United States
PG

Pierre Giglio, M.D.

Ohio State University Comprehensive Cancer Center
Columbus, United States
AZ

Alicia Zukas, MD

Medical University of South Carolina
Charleston, United States
David Cachia, MD (he/him/his)

University of Massachusetts
SL

Scott M Lindhorst, M.D.

Medical University of South Carolina
Charleston, United States

Atypical and anaplastic meningiomas (WHO Grade 2 and WHO Grade 3 respectively) represent a subgroup of meningiomas that tend to have higher rates of recurrence with associated’s higher morbidity and mortality than the more common WHO Grade 1 meningiomas. Our laboratory data demonstrated that galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, is highly expressed in these meningioma subtypes as compared to normal brain tissue. However, the root of the profoundly immunosuppressive tumor microenvironment in meningioma cells is not fully understood. To address this, we used a Gal-3 inhibitor TD 139 paired with low-intensity non-invasive transcranial direct current stimulation (tDCS) to suppress tumor growth and enhance the immune response in the preclinical model. Treatment of tDCS (50 mV/mm for 30 min) followed by 1 mM of TD139 induced cell death in anaplastic meningioma in vitro human triple co-culture model but has no effect on mouse cortical neurons. Furthermore, we demonstrated that inhibiting of Gal-3 expression significantly decreased the protein levels of urokinase-type plasminogen activator receptor as well as phosphorylation of Akt and upregulates Bax expression. Treatment with TD139 (1mg/kg per day for 14 days) with tDCS [350 μA (1 x 30 min/day) for 7 times (within 14 Days) showed a significantly (∼60%) decrease in MGS2 atypical meningioma tumor growth in orthotopic allograft model (at Day 41). The percent survival of tumor-bearing mice treated with TD139 and tDCS was significantly higher than an untreated tumor or single treatment. Following TD139 plus tDCS treatment, our results demonstrated significant meningioma cell death via a decrease in NDRG4 (Meningioma marker) and were associated with downregulation of Ki-67 in treated tumors. Based on our substantial preliminary data, we believe that this proposed translational work has the potential to be an effective combinational modality form of treatment for atypical and malignant meningiomas.