Gene therapy and the adeno associated virus in the treatment of genetic and acquired ophthalmic diseases in humans: trials, future directions and safety considerations

Voretigene neparvovec-rzyl was recently approved for the treatment of Leber Congenital Amaurosis, and the use of gene therapy for eye disease is attracting even greater interest. The eye has immune privileged status, is easily accessible, requires a reduced dosage of therapy due to its size, and is highly compartmentalized, significantly reducing systemic spread. Adeno-associated virus (AAV), with its low pathogenicity, prolonged expression profile and ability to transduce multiple cell types, has become the leading gene therapy vector. Target diseases have moved beyond currently untreatable inherited dystrophies to common, partially treatable acquired conditions such as exudative AMD and glaucoma, but use of the technology in these conditions imposes added obligations for caution in vector design. This review discusses the current status of AAV gene therapy trials in genetic and acquired ocular diseases, and explores new scientific developments which could help ensure effective and safe use of the therapy in the future

Is there a place on the shelf for Aliskiren?

Increased renin-angiotensin-aldosterone system (RAAS) activity contributes to target-organ damage and increases cardiovascular risk by elevating blood pressure (BP) and through direct effects on the heart, kidneys, brain, and vascular endothelium. Pharmacologic blockade of RAAS effectively reduces BP and limits or reverses various forms of target-organ damage, including cardiac heart failure, coronary artery disease, chronic kidney disease, and left ventricular hypertrophy. Direct renin inhibitors selectively inhibit human renin and have a therapeutic potential similar to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Aliskiren is the only orally active direct renin inhibitor that has been approved for the treatment of hypertension and has been shown to have favorable effects on target-organ damage. It effectively reduces BP and has favorable effects on heart failure and proteinuria in diabetic patients. Additional outcome trials are needed to establish the role of this new class of antihypertensive medication in preventing cardiovascular outcomes