Translational Medical Research Commons^™

Evolution Of The Alpha-1 Antitrypsin Muscle Gene Therapy: Translation From Clinical Trial To Benchtop And Back Again, Alisha M. Gruntman, Gwladys Gernoux, Gensheng Wang, Janet Benson, Jeff Chulay, Dave Knop, Christian Mueller, Terence R. Flotte

Christian Mueller

Alpha-one antitrypsin (AAT) deficiency is a genetic disease affecting the lungs due to inadequate anti-protease activity in the pulmonary interstitium. On-going human trials use intra-muscular delivery of adeno-associated virus (rAAV1), allowing expressing myofibers to secrete normal (M)AAT protein. In the Phase IIa trial, patients in the highest dose cohort (6x1012vg/kg) were given 100 intra-muscular (IM) injections of undiluted vector, with serum AAT levels still substantially below target levels. Previous work has shown that delivering rAAV vector to the musculature via limb perfusion leads to widespread gene expression in myofibers. We hypothesize that widespread delivery would result in an overall increase …

Therapeutic Approaches To Aggressive Carcinomas Based On A Novel Vegf/Neuropilin Autocrine Pathway, Hira Lal Goel, Arthur M. Mercurio

Arthur M. Mercurio

Summary: Autocrine VEGF signaling in tumor cells contributes to de-differentiation and function of tumor initiating/stem cells. NRP2 is the nexus of a signaling pathway that promotes de-differentiation and sustains tumor initiating/stem sells. Anti-NRP2 therapy is worth pursuing, especially for high-grade cancers. Therapeutic Abs are available. This presentation was part of the retreat mini-symposium entitled: Biomarker Discovery and Targeted Therapeutics in Cancer.

Statin Discontinuation Among Nursing Home Residents With Advanced Dementia, Jennifer Tjia, Sarah L. Cutrona, Daniel J. Peterson, Becky A. Briesacher

Jennifer Tjia

Background: Statin use in elderly individuals with life-limiting illness such as advanced dementia is controversial.

Objective: To describe factors associated with statin discontinuation and estimate impact of discontinuation on 28-day hospitalizations in nursing home (NH) residents with advanced dementia.

Methods: Retrospective cohort study of NH residents ≥ 65 years with recent progression to advanced dementia from 5 large U.S. states drawn from the 2007-2008 Minimum Data Set 2.0. We identified residents using statins. Clinical characteristics and 28-day hospitalization risk were compared for residents discontinuing and continuing statins. Multivariable Cox proportional hazard models identified factors associated with time to statin discontinuation …