mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.

Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.

Illicit drug use among pregnant women enrolled in treatment for cigarette smoking cessation.

INTRODUCTION: Smoking during pregnancy is the leading preventable cause of poor pregnancy outcomes in the United States. In population studies and nationwide surveys, pregnant smokers report more illicit drug use than pregnant nonsmokers. The purpose of this study was to examine the prevalence of illicit drug use among pregnant women enrolled in clinical trials for smoking cessation. METHODS: Urine specimens from 115 pregnant women were tested for illicit drug use during a study intake visit (~10th week of pregnancy) and during the final antepartum (FAP) smoking-status assessment (~28th week of pregnancy). Participants smoked about 18 cigarettes/day prepregnancy, were generally young (<25 years), Caucasian, with a high school education and without private insurance. RESULTS: About 34% of specimens from the intake visit and 25% of those from the FAP assessment tested positive for an illicit drug. The most common drug detected was marijuana (90% of positive specimens), followed by opioids (18%), cocaine (5%), benzodiazepines (3%), and methadone (3%). None tested positive for amphetamines. The majority of women (53%) who tested positive for an illicit substance at intake also tested positive at the FAP assessment. CONCLUSIONS: Approximately a quarter to a third of pregnant women enrolled in these smoking-cessation trials were determined to be using illicit drugs, with marijuana use being the most prevalent. Those providing smoking-cessation services to pregnant women may want to be prepared to assist with obtaining services for other drug use as well.