Leiden University Medical Center

Genetic studies of body mass index yield new insights for obesity biology

Position Paper of the European Society of Cardiology Working Group Cellular Biology of the Heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure

Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.

Biology and novel treatment options for XLA, the most common monogenetic immunodeficiency in man

INTRODUCTION: X-linked agammaglobulinemia (XLA) is the most common primary immunodeficiency in man, and is caused by a single genetic defect. Inactivating mutations in the Bruton's tyrosine kinase (BTK) gene are invariably the cause of XLA,. XLA is characterized by a differentiation arrest at the pre-B cell stage, the absence of immunoglobulins and recurrent bacterial infections, making it an insidious disease that gradually disables the patient, and can result in death due to chronic lung disease. Current treatment involves prophylactic antibiotics and immunoglobulin infusions, which are non-curative. This disease is a good candidate for curative hematopoietic stem cell (HSC)-based gene therapy, which could correct the B cell and myeloid deficiencies. AREAS COVERED: This paper reviews the basic biology of BTK in B cell development, the clinical features of XLA, and the possibilities of gene therapy for XLA, covering the literature from 1995 to 2010. EXPERT OPINION: Work from various laboratories demonstrates the feasibility of using gene-corrected HSCs to complement the immune defects of Btk-deficiency in mice. We propose that it is timely to start clinical programs to develop stem cell based therapy for XLA, using gene-corrected autologous HSC.