Wilson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Wilson's Disease, including details on treatment, causes, symptoms, medication.

Structure-based design of kinetic stabilizers that ameliorate the transthyretin amyloidoses.

Connelly S, Choi S, Johnson SM, Kelly JW, Wilson IA

Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Small molecules that bind to normally unoccupied thyroxine (T(4)) binding sites within transthyretin (TTR) in the blood stabilize the tetrameric ground state of TTR relative to the dissociative transition state and dramatically slow tetramer dissociation, the rate-limiting step for the process of amyloid fibril formation linked to neurodegeneration and cell death. These so-called TTR kinetic stabilizers have been designed using structure-based principles and one of these has recently been shown to halt the progression of a human TTR amyloid disease in a clinical trial, providing the first pharmacologic evidence that the process of amyloid fibril formation is causative. Structure-based design has now progressed to the point where highly selective, high affinity TTR kinetic stabilizers that lack undesirable off-target activities can be produced with high frequency.

Published 5 February 2010 in Curr Opin Struct Biol.
Full-text of this article is available online (may require subscription).

Articles on Wilson's Disease published 5 February 2010:

Perfluorocarbon Dosing when Starting Partial Liquid Ventilation: Haemodynamics and Cerebral Blood Flow in Preterm Lambs.   Neonatology, 97(2): 144-153.

Background: Very preterm neonates can have severe lung disease and are prone to brain injury if cerebral blood flow fluctuates. Partial liquid ventilation (PLV) may benefit the lung disease, but it is unknown whether the administration of intratracheal perfluorocarbon when starting PLV affects haemodynamics or cerebral blood flow. Objectives: To determine if haemodynamics or cerebral blood flow are affected in preterm lambs receiving a dose of perfluorocarbon when starting PLV. Methods: Sixteen ... [Abstract] [Full-text]

Patterns of enrollment of infants with central nervous system tumours on cooperative group studies: a report from the canadian pediatric brain tumour consortium.   J Neurooncol.

In children under the age of 3, the most common solid tumours are brain tumors. Treatment for many of these patients includes surgery, chemotherapy and rarely radiation therapy. Many clinical trials have been performed in an attempt to establish the best treatment for these patients. Patients enrolled on clinical trials contribute to the establishment of the best therapy. We performed a national survey of all children less than the age of three with brain tumours and examined the contribution ... [Abstract] [Full-text]

A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone.   Proc Natl Acad Sci U S A.

Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. ... [Abstract] [Full-text]

Articles on Wilson's Disease published 4 February 2010:

Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper.   Autoimmun Rev, 9(4): 216-223.

Rheumatoid arthritis (RA) is a crippling joint disease affecting over 20million people worldwide. The cause of RA is most probably linked to the triad of microbial trigger, genetic association and autoimmunity and can be explained using the philosophical method of Karl Popper or Popperian sequences. Ten "Popper sequences" have been identified which point to the urinary microbe Proteus mirabilis as the cause of RA: Popper sequence 1 establishes that HLA-DR4 lymphocytes injected into a ... [Abstract] [Full-text]

A CD1d-Dependent Antagonist Inhibits the Activation of Invariant NKT Cells and Prevents Development of Allergen-Induced Airway Hyperreactivity.   J Immunol, 184(4): 2107-15.

The prevalence of asthma continues to increase in westernized countries, and optimal treatment remains a significant therapeutic challenge. Recently, CD1d-restricted invariant NKT (iNKT) cells were found to play a critical role in the induction of airway hyperreactivity (AHR) in animal models and are associated with asthma in humans. To test whether iNKT cell-targeted therapy could be used to treat allergen-induced airway disease, mice were sensitized with OVA and treated with ... [Abstract] [Full-text]

Articles on Wilson's Disease published 3 February 2010:

Increased expression and cellular localization of spermine oxidase in ulcerative colitis and relationship to disease activity.   Inflamm Bowel Dis.

BACKGROUND:: Polyamines are important in cell growth and wound repair, but have also been implicated in inflammation-induced carcinogenesis. Polyamine metabolism includes back-conversion of spermine to spermidine by the enzyme spermine oxidase (SMO), which produces hydrogen peroxide that causes oxidative stress. In ulcerative colitis (UC), levels of spermine are decreased compared to spermidine. Therefore, we sought to determine if SMO is involved in UC. METHODS:: Colon biopsies and clinical ... [Abstract] [Full-text]

Excellent immunological recovery following CODOX-M/IVAC, an effective intensive chemotherapy for HIV-associated Burkitt's lymphoma.   AIDS.

OBJECTIVE AND DESIGN:: To retrospectively describe the recovery of cellular immunity and the clinical outcome of 30 patients with HIV-associated Burkitt's lymphoma (HIV-BL), who were treated with the intensive chemotherapy CODOX-M/IVAC and HAART as part of their standard care. PATIENTS AND METHODS:: Seventy-three percent of the patients had high-risk disease, defined by stage, performance status, extranodal sites and lactate dehydrogenase. The median CD4 cell count at diagnosis of HIV-BL was ... [Abstract] [Full-text]

Genetic influences modulating the radiological severity of rheumatoid arthritis.   Ann Rheum Dis.

This review focuses on the contribution of genetic markers to the severity of radiological damage in rheumatoid arthritis (RA). Currently available biomarkers of more severe disease include elevated erythrocyte sedimentation rates or C-reactive protein levels and rheumatoid factor (RF) or anticyclic citrullinated protein antibodies positivity; however, these biomarkers explain a relatively modest proportion of the variance in radiological damage. An important role of genetic factors on RA ... [Abstract] [Full-text]

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