However, the dosage used in the Phase III trial may have been too low to be efficacious.A Phase II study with maribavir demonstrated that prophylaxis with maribavir displayed strong antiviral activity, as measured by statistically significant reduction in the rate of reactivation of CMV in recipients of hematopoietic stem cell/bone marrow transplants. In an intent-to-treat analysis of the first 100 days after the transplant, the number of subjects who required pre-emptive anti-CMV therapy was statistically significantly reduced with maribavir compared to placebo.ViroPharma conducted a Phase III clinical study to evaluate the prophylactic use for the prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplant patients. In February 2009, ViroPharma announced that the Phase III study failed to achieve its goal, showing no significant difference between maribavir and a placebo at reducing the rate at which CMV DNA levels were detected in patients.The safety and efficacy of maribavir were evaluated in a Phase III, multicenter, open-label, active-controlled trial that compared maribavir with a treatment assigned by a researcher running the study, which could include one or two of the following antivirals used to treat cytomegalovirus: ganciclovir, valganciclovir, foscarnet, or cidofovir. In the study, 352 transplant recipients with cytomegalovirus infections who did not respond (with or without resistance) to treatment randomly received maribavir or treatment assigned by a researcher for up to eight weeks. The study compared the two groups plasma cytomegalovirus DNA concentration levels at the end of the studys eighth week, with efficacy defined as having a level below what is measurable.
Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.It is a lethal rhizomelic (malformations which result in short, underdeveloped limbs) form of dwarfism, exhibiting both skeletal dysplasia (malformations of bone) and fibroblastic dysplasia (abnormal development of fibroblasts, specialized cells that make up fibrous connective tissue, which plays a role in the formation of cellular structure and promotes healing of damaged tissues). Death caused by complications of fibrochondrogenesis occurs in infancy. Presentation
Fibrochondrogenesis is a congenital disorder presenting several features and radiological findings, some which distinguish it from other osteochondrodysplasias. These include: fibroblastic dysplasia and fibrosis of chondrocytes (cells which form cartilage); and flared, widened
long bone metaphyses (the portion of bone that grows during childhood).Other prominent features include dwarfism, shortened ribs that have a concave appearance, micrognathism (severely underdeveloped jaw), macrocephaly (enlarged head), thoracic hypoplasia (underdeveloped chest), enlarged stomach, platyspondyly (flattened spine), and the somewhat uncommon deformity of bifid tongue (in which the tongue appears split, resembling that of a reptile). Cause
The cause of platyspondyly in fibrochondrogenesis can be attributed in part to odd malformations and structural flaws found in the vertebral bodies of the spinal column in affected infants.Fibrochondrogenesis alters the normal function of chondrocytes, fibroblasts, metaphyseal cells and others associated with cartilage, bone and connective tissues. Overwhelming
disorganization of cellular processes involved in the formation of cartilage and bone (ossification), in combination with fibroblastic degeneration of these cells, developmental errors and systemic skeletal malformations describes the severity of this lethal osteochondrodysplasia.