What's new and what's next for gene therapy in Pompe disease?

INTRODUCTION: Pompe disease is an autosomal recessive disorder caused by a deficiency of acid-α-glucosidase (GAA), an enzyme responsible for hydrolyzing lysosomal glycogen. A lack of GAA leads to accumulation of glycogen in the lysosomes of cardiac, skeletal, and smooth muscle cells, as well as in the central and peripheral nervous system. Enzyme replacement therapy has been the standard of care for 15 years and slows disease progression, particularly in the heart, and improves survival. However, there are limitations of ERT success, which gene therapy can overcome. AREAS COVERED: Gene therapy offers several advantages including prolonged and consistent GAA expression and correction of skeletal muscle as well as the critical CNS pathology. We provide a systematic review of the preclinical and clinical outcomes of adeno-associated viral mediated gene therapy and alternative gene therapy strategies, highlighting what has been successful. EXPERT OPINION: Although the preclinical and clinical studies so far have been promising, barriers exist that need to be addressed in gene therapy for Pompe disease. New strategies including novel capsids for better targeting, optimized DNA vectors, and adjuctive therapies will allow for a lower dose, and ameliorate the immune response.

Neonatal invasive candidiasis: updates on clinical management and prevention.

Neonatal invasive candidiasis is an important cause of morbidity and mortality in preterm infants. The incidence of invasive candidiasis in this population has been declining in high-income settings, largely due to preventive measures, although there are still considerable variations in incidence between health-care centres. Surveillance data and large, multicentre studies in lower-income settings are not available, although preventive measures in these settings have been shown to decrease the incidence of neonatal invasive candidiasis. Understanding risk factors and pathogenesis are key to the prevention of invasive candidiasis. The difficulty of a definitive diagnosis of invasive candidiasis and the high risk for death or substantial neurodevelopmental impairment, even with appropriate treatment, further increase the need for effective preventive measures. In this Review, we examine the pathogenesis, clinical presentation, and diagnosis of invasive candidiasis. We highlight commonly used and emerging preventive and prophylactic measures, including standardised central line care, antibiotic stewardship, antifungal prophylaxis, and probiotics. Finally, we provide updates on empirical treatment, clinical management in confirmed cases of invasive candidiasis, and antifungal pharmacotherapy.