cusabio2015的部落格

Scientists from Australia and the Netherlands have identified a diagnostic biomarker of a rare childhood disease called mevalonate kinase deficiency (MKD). The study “Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency” is published online 10 May 2017 in the Journal of Allergy and Clinical Immunology.

MKD is a rare, inherited auto-inflammatory disease that disrupts the production of cholesterol and isoprenoids. The disease is most often caused by mutation of the MVK gene. This gene provides instructions for making the mevalonate kinase (MVK) enzyme, which plays an important role in the synthesis of cholesterol and isoprenoids. Patients usually experience recurrent episodes of high fever, which typically begin during infancy and can persist into adulthood. The severity of the disease varies from person to person. There two types of MKD: hyperimmunoglobulinemia D syndrome (HIDS) and mevalonic aciduria (MVA).

Investigators, including Chung-Ping Liao, Reid C. Booker, Sean J. Morrison and Lu Q. Le from the University of Texas Southwestern Medical Center (UT Southwestern), have stumbled upon a finding that may lead to a cure for balding and hair graying.

The study, “Identification of hair shaft progenitors that create a niche for hair pigmentation,” appears in an advance online publication by the journal Genes & Development.

Researchers have discovered a tumor suppressor in human liver cancer. Although it is not easy to selectively target the tumor suppressor, the study extends our understanding of liver cancer pathogenesis.

SCRIB is a scaffold protein that in humans is encoded by the SCRIB gene. This protein is found as a membrane protein and it regulates the establishment of apical-basal cell polarity of the epithelial tissues. Previous studies have shown that SCRIB also plays a role in cancer progression. For example, SCRIB is mislocalized to the cytoplasm in breast and prostate cancer.

A study co-led by Torunn Fiskerstrand at Haukeland University Hospital in Norway and Michele Ramsay at the University of the Witwatersrand in South Africa has revealed genetic mutation responsible for an common skin disease known as keratolytic winter erythema (KWE).

KWE is also known as Oudtshoorn skin and Erythrokeratolysis hiemalis ichthyosis. Typical symptoms include cyclical erythema, hyperkeratosis, and peeling of the skin of the palms and soles. The condition is worse in the winter. KWE is quite prevalent among the South African Afrikaans-speaking Caucasoid population. According to estimates, its prevalence in this population is about 1/7200. Initially KWE was believed to be unique to South Africa, but recent studies have shown that individuals in other countries may also develop the disease.

Heart disease is an umbrella term including blood vessel disease, heart rhythm problems, and congenital heart defects. These diseases become the number one killer of both men and women worldwide. Sometimes, patients with heart disease need a heart transplantation, which is the ultimate choice.

Heart transplantation is a surgery that removes a diseased heart and replaces it with a healthy heart from a deceased donor. This surgery was first performed in a person with severe heart disease in 1967. It has been 50 years since the first human heart transplant.

Led by scientists from Brown University and Brown Institute for Brain Science in the United States and the University of Cologne in Germany, a study (Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models, eLife (2017)) now offers new clues to Spinal Muscular Atrophy (SMA), a genetic disease that attacks motor neurons in the brain and spinal cord.

SMA occurs in 1 in 10,000 births, making it the most commonly inherited motor neuron disease in infants and children. Over time, the disease can cause skeletal muscle weakness, atrophy, and premature death in the majority of the patients. More than 95% of patients with SMA have a homozygous deletion or mutation of the SMN1 (Survival Motor Neuron 1) gene, resulting in reduced Survival of Motor Neuron (SMN) protein levels. SMN is found throughout the body, with high levels in the spinal cord. This protein normally plays a role in processing messenger RNA (mRNA), a family of RNA molecules that are crucial for protein synthesis. Moreover, evidence shows that SMN may have additional functions in nerve cells. If we can better understand the consequences of SMN loss, it may lead to new treatment strategies for SMA.

Neuromyelitis optica (NMO) is a rare autoimmune disease in which immune system cells and antibodies attack the spinal cord and the optic nerves. This relapsing-remitting disease can eventually lead to paralysis and blindness. Early diagnosis of NMO is critical. The majority of NMO patients have anti-AQP4 antibody, or called the NMO antibody, in their blood. So this antibody is considered a biomarker for NMO. Aquaporins (AQPs) are proteins that transport water across cell membranes. Blood tests to detect NMO-IgG are used to help doctors diagnose the disease.

Now a study of the University of Colorado Anschutz Medical Campus sheds light on the mechanism of NMO. The researchers used a custom STED microscope that can show living cell structures in great detail to study anti-AQP4 antibody. With the help of the STED microscope, they observed clusters of antibodies on astrocytes, the brain cell target of the autoimmune response in NMO. Lead researcher Professor Jeffrey Bennett said that "This could potentially correspond with their ability to damage the cells." The study appears in Biophysical Journal.

As the number one cause of dementia, Alzheimer's disease (AD) affects millions of people worldwide. AD was first described in 1907, but until now treatment is still limited to drugs that only reduce symptoms, such as donepezil, galantamine, rivastigmine, and memantine. The two hallmarks of AD are the extracellular neuritic plaque, which mainly composed of the amyloid-beta peptide, and the intracellular neurofibrillary tangle, which is made up of a different protein called tau. Some studies suggest these neuritic plaques and neurofibrillary tangles damage nerve cells in the brain, resulting in impairment of certain brain functions. But other studies indicate that people with high amyloid levels may show no symptoms of AD. More research is required to better understand the pathogenesis of the disease.

Now a study in the latest edition of eLife has demonstrated that low levels of the protein NPTX2 in the brain are associated with cognitive decline in individuals with AD. The study is led by Paul Worley at Johns Hopkins University School of Medicine.

Hypophosphatasia (HPP) is a rare, genetic, metabolic disease that affects the development of bones and teeth. The disease was initially recognized in 1948. Now it is well established that HPP results from mutations in the alkaline phosphatase (ALP) gene ALPL, which encodes tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). TNSALP is a phosphomonoesterase. Mutations in ALPL leads to low alkaline phosphatase activity levels and ultimately to rickets and osteomalacia. Individuals with HPP may experience metatarsal and femoral stress fractures or pseudofractures, pathological fractures after minimal trauma, muscle and joint pain, and osteomalacia. Currently, the diagnosis of HPP is mainly based on low serum ALP enzyme activity, high endogenous levels of TNSALP substrates, and ultimately mutations in the ALPL gene.

It is believed that bone anabolic and/or enzyme replacement treatment strategies could treat HPP. One such therapy called asfotase alfa (Strensiq, Alexion) has already been approved for long-term treatment of pediatric-onset HPP in several countries. Previous clinical trials have shown that asfotase alfa improve survival of patients with severe perinatal/infantile onset of HPP. But due to  regulatory specifications, access to asfotase alfa is limited.

PD-1, also known as Programmed cell death protein 1 or CD279, is considered an immune check point protein. It functions as an inhibitory receptor expressed on activated T cells and serves as an important drug target in cancer treatment. Many drugs that target PD-1 are approved for the treatment of cancers, including advanced melanoma, Hodgkin lymphoma, lung, kidney, bladder and head and neck cancers. There are examples of cancer immunotherapy agents that target PD-1: Nivolumab, Pembrolizumab, Pidilizumab.

Now a company called Agenus initiates a phase 1/2 clinical trial of a new drug targeting PD-1. The drug is an anti-PD-1 antibody, known as AGEN2034. The aim of the study is to analyze the effectiveness and safety of the antibody in individuals with advanced solid tumors and to determine the recommended dose of AGEN2034 in individuals with second line cervical cancer. Dr Garo Armen, a member of Agenus, stated that this clinic trial is part of their research to develop combination therapies. One combination treatment strategy is combine PD-1 antagonist with CTLA-4 directed antibody.