No abstract

Hutchinson–Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

Adhesive shoulder capsulitis, or arthrofibrosis, describes a pathological process in which the body forms excessive scar tissue or adhesions across the glenohumeral joint, leading to pain, stiffness and dysfunction. It is a debilitating condition that can occur spontaneously (primary or idiopathic adhesive capsulitis) or following shoulder surgery or trauma (secondary adhesive capsulitis). Here, we review the pathophysiology of adhesive shoulder capsulitis, highlighting its clinical presentation, natural history, risk factors, pathoanatomy and pathogenesis. Both current non-operative and operative treatments for adhesive capsulitis are described, and evidence-based studies are presented in support for or against each corresponding treatment. Finally, the review also provides an update on the gene expression profile of adhesive capsulitis and how this new understanding can help facilitate development of novel pharmacological therapies.