Arsenic trioxide demonstrates efficacy in a mouse model of preclinical systemic sclerosis.

Background: Uncontrolled T-cell activation plays a key role in systemic sclerosis (SSc). Arsenic trioxide (ATO) has immunological effects and has demonstrated potential in preclinical SSc models. In this study, we assessed the efficacy of ATO in Fra2 transgenic (Fra2) mice, which develop severe vascular remodeling of pulmonary arterioles and nonspecific interstitial pneumonia-like lung disease, closely resembling human SSc-associated pulmonary hypertension, therefore partially resembling to the SSc human disease.

Optimal combination of arsenic trioxide and copper ions to prevent autoimmunity in a murine HOCl-induced model of systemic sclerosis.

Introduction: Systemic sclerosis (SSc) is a rare chronic autoimmune disease characterized by diffuse fibrosis of the skin and internal organs and vascular abnormalities. The etiology and physiopathology are complex due to the heterogeneity of its overall clinical presentation. Arsenic trioxide (ATO) has been proven to be effective against SSc, sclerodermatous Graft-versus-Host Disease, multiple sclerosis, Crohn's disease or systemic lupus erythematosus animal models and has demonstrated promising effects in human clinical trials.

A Fenton-like cation can improve arsenic trioxide treatment of sclerodermatous chronic Graft-versus-Host Disease in mice.

Graft-versus Host Disease (GvHD) is a major complication of hematopoietic stem cell transplant. GvHD is characterized by the chronic activation of immune cells leading to the development of systemic inflammation, autoimmunity, fibrosis and eventually death. Arsenic trioxide (ATO) is a therapeutic agent under clinical trial for the treatment of patients with systemic lupus erythematosus (SLE) and chronic GvHD (cGvHD).

High Response Rate and Corticosteroid Sparing with Arsenic Trioxide-Based First-Line Therapy in Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) occurs in 20% to 50% of recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Corticosteroids (CS) remain the first-line therapy but have suboptimal efficacy and carry a risk of long-term side effects. New agents with a better safety profile and higher efficacy are urgently needed.

Safety and efficacy of low-dose intravenous arsenic trioxide in systemic lupus erythematosus: an open-label phase IIa trial (Lupsenic).

Background: Lupus animal model has shown that arsenic trioxide (ATO), a treatment of acute promyelocytic leukaemia, could be effective in SLE. This is the first clinical study to determine the safety and efficacy of a short course of intravenous ATO in patients with active SLE.

Methods: This phase IIa, open-label, dose-escalating study enrolled 11 adult SLE patients with a non-organ threatening disease, clinically active despite conventional therapy.

Neuromuscular expression of the BTB/POZ and zinc finger protein myoneurin.

Myoneurin belongs to the BTB/POZ and zinc finger protein family whose members have been implicated in regulatory functions of gene expression. Myoneurin has been identified in various tissues, but muscle is a privileged site of myoneurin gene transcription. We examined the neuromuscular expression of myoneurin during development and after axotomy.

The HERV-W/7q family in the human genome. Potential for protein expression and gene regulation.

A new family of human endogenous retroviruses has recently been discovered. The best known example of a full length member of this family, HERV-W/7q, is located on chromosome 7. HERV-W/7q is characterized by a long open reading frame within its env gene which is expressed in various tissues, and mainly in placenta, as a protein that we called enverin.

Induction of cell death in rat brain by a gliotoxic factor from cerebrospinal fluid in multiple sclerosis.

The cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients contains a 17 kDa glycoproteic factor with gliotoxic properties in vitro. In order to study the physiopathological role of this gliotoxic factor in vivo, we have injected a partially purified preparation and appropriate controls in rat CSF and investigated whether it induces cell death in the rat central nervous system (CNS), 10 days and 3 months after injection. We used the TUNEL assay in association with specific immunohistochemistry to characterize dying cells in the gliotoxic factor- treated rat CNS.

Motoneuron morphological alterations before and after the onset of the disease in the wobbler mouse.

The wobbler mutant mouse displays a recessively inherited neurological disease with degeneration of motoneurons and is considered to be an animal model for human motoneuron diseases. Mutant mice can be clinically recognised at about 3-4 weeks of age but a polymorphic marker close to the wobbler gene offers the opportunity of a preclinical diagnosis. Using this polymorphic marker we performed morphometric (cell size) analysis of spinal cord motoneurons from 10 to 40 days post natal (PN).