A BMP/Activin A Chimera Induces Posterolateral Spine Fusion in Nonhuman Primates at Lower Concentrations Than BMP-2.

Background: Supraphysiologic bone morphogenetic protein (BMP)-2 concentrations are required to induce spinal fusion. In this study, a BMP-2/BMP-6/activin A chimera (BV-265), optimized for BMP receptor binding, delivered in a recombinant human collagen:CDHA [calcium-deficient hydroxyapatite] porous composite matrix (CM) or bovine collagen:CDHA granule porous composite matrix (PCM), engineered for optimal BV-265 retention and guided tissue repair, was compared with BMP-2 delivered in a bovine absorbable collagen sponge (ACS) wrapped around a MASTERGRAFT Matrix (MM) ceramic-collagen rod (ACS:MM) in a nonhuman primate noninstrumented posterolateral fusion (PLF) model.

Methods: In vivo retention of 125I-labeled-BV-265/CM or PCM was compared with 125I-labeled-BMP-2/ACS or BMP-2/buffer in a rat muscle pouch model using scintigraphy.

Activation of Bone Remodeling Compartments in BMP-2-Injected Knees Supports a Local Vascular Mechanism for Arthritis-Related Bone Changes.

Background: Synovial membrane-derived factors are implicated in arthritis-related bone changes. The route that synovial factors use to access subchondral bone and the mechanisms responsible for these bone changes remain unclear. A safety study involving intra-articular injection of bone morphogenetic protein-2 (BMP-2)/calcium phosphate matrix (CPM) or CPM addresses these issues.

A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix.

Bone morphogenetic protein (BMP)/carriers approved for orthopedic procedures achieve efficacy superior or equivalent to autograft bone. However, required supraphysiological BMP concentrations have been associated with potential local and systemic adverse events. Suboptimal BMP/receptor binding and rapid BMP release from approved carriers may contribute to these outcomes.

New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities.

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS.

Clarithromycin overcomes resistance to lenalidomide and dexamethasone in multiple myeloma.

The combination of clarithromycin, lenalidomide and dexamethasone (BiRd) has led to highly durable responses in newly diagnosed myeloma. However, the ability of clarithromycin to overcome resistance to lenalidomide and dexamethasone (Rd) is not known. To study this, we performed a retrospective analysis of 24 patients with myeloma for which clarithromycin was added to Rd at the time of progression on Rd.