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CARM1 (coactivator-associated arginine methyltransferase 1) belongs to a family of enzymes known as PRMTs (protein arginine methyltransferases), which can introduce arginine methylation. CARM1 is also referred to as PRMT4. Protein methylation, the addition of a methyl group to target proteins, is one type of post-translational modification that can change the function of the target proteins.
CARM1 has been reported to be overexpressed in breast cancer, and its overexpression is associated with high-grade tumors and poorer prognosis. So CARM1-specific inhibitors are considered a promising breast cancer therapy. However, until now only few targets of CARM1 have been identified, and how it recognizes these targets remains unclear.

A study in the Proceedings of the National Academy of Sciences (GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant-driven pancreatic tumorigenesis in mice) shows that inhibiting a specific protein may be a way to combat the deadly pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for 95% of all cases of pancreatic cancer, remains an aggressive type of malignant tumor in need of more effective therapies. The five-year survival rate is only about 5%, though surgery offers the only opportunity for a cure. In the United States alone, PDAC killed 39,590 people in 2014.

Patients with Churg-Strauss Syndrome (CSS) may benefit from an anti-IL5 monoclonal antibody. This is the result of a study (Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis) published May 18, 2017 in New England Journal of Medicine.
Churg-Strauss Syndrome (CSS), also known as Eosinophilic granulomatosis with polyangiitis (EGPA), is an extremely rare autoimmune condition marked by blood vessel inflammation. It can impair multiple organ systems, such as the lungs, skin, nerves and stomach. The disease generally affects individuals with a history of asthma or allergies. Asthma, eosinophils, fevers, shortness of breath, cough, wheezing, runny nose, sinusitis, and rashes are common symptoms. Left untreated, the disease can be life-threatening.

Alzheimer's disease (AD) was firstly described and named after a psychiatrist and pathologist Dr. Alois Alzheimer in 1906. It is an irreversible, progressive brain disorder that affects cognitive functions. Symptoms usually starts in patients’ mid-60s, but can also occur earlier. According to estimated, 5 million people in the USA have the disease, for which currently there are no treatments to stop or reverse the progression. Exiting therapies only temporarily improve symptoms. Its incidence is rising in line with the aging population. Mechanisms of AD have yet completely understood.

Published 26 April 2017 in Alzheimer’s Research and Therapy, a new study, carried out by Doris Lambracht-Washington, Min Fu, Pat Frost and Roger Rosenberg at UT Southwestern Medical Center, now reports a DNA vaccine that could protect against toxic proteins associated with AD. The researchers demonstrated that a DNA Aβ42 trimer vaccine led to high levels of antibody responses in rhesus macaques.

In the past, there are limited treatment options for people with advanced kidney cancer. These patients tend to have poor outcomes. In recent years, the emergence of novel combination treatments, such as the combination of nivolumab and ipilimumab, have prolonged the survival of some patients. However, there are a still a subpopulation of patients who do not respond to these combination treatments.
Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody used in the treatment of several cancers such as inoperable or metastatic melanoma, metastatic squamous non-small cell lung cancer, primary or metastatic urothelial carcinoma, and renal cell carcinoma. It works by blocking a signal that would have prevented activated T cells from attacking the cancer. Ipilimumab is a also monoclonal antibody and it activates the immune system by a protein that downregulates that immune system, CTLA-4. (Cusabio offers polyclonal antibody.)

Since 2014, the lethal Ebola virus has swept many countries on the planet, particularly Liberia, Sierra Leone, and Guinea in West Africa. Ebola becomes an emerging infectious disease for which there is no known cure. Now, making progress toward a vaccine and therapy against Ebola, researchers reporting in Cell have identified natural human antibodies with the potential to provide broad protection against Ebolaviruses.
Therapies based on monoclonal antibody has shown promise for treatment of Ebola infections. However, one thing that limits their application is that most antibody therapies target just one specific ebolavirus due to their species-specific recognition of the viral glycoprotein (GP). One experimental therapy called ZMappTM, which comprises thress chimeric monclonal antibodies, is specific for Ebola virus, or called Zaire ebolavirus, but is ineffective against two other ebolaviruses known as Sudan virus and Bundibugyo virus. (CusAb strives to provide the excellent products such as Biotin conjugated antibody for researchers.)

PD-1, a 55 kDa transmembrane protein, is an immune checkpoint receptor expressed by activated T cells, B cells, and myeloid cells. It is important for the induction of immune tolerance. Mice lacking PD-1 exhibit a breakdown of peripheral tolerance and show multiple autoimmune features. Tumor cells often express elevated levels of PD-L1, which is the ligand for PD-1, and this help them to evade the body’s immune attacks. Monoclonal antibodies targeting PD-1/PD-L1 interaction are promise in treating various cancers. These antibodies have already been known to unleash T cells, but how they affect macrophages remains unclear. (Cusabio offers Biotin conjugated antibody.)

Now, researchers from Stanford University School of Medicine, University Hospital Basel, and Yale University School of Medicine have found that those antibodies also prompt immune cells to engulf and devour cancer cells. In a paper published online 17 May 2017 in Nature, the researchers report how they made the discovery, which will expand the use of PD-1/PD-L1 blockade antibodies in cancer treatment.

Investigators from Germany have revealed the protective role of a protein in inflammatory bowel disease (IBD). The protein, called CD14, could be targeted to treat or prevent this debilitating and even life-threatening disease.

Inflammatory bowel disease (IBD), a group of diseases that involve inflammation of part or all of the digestive tract and predominantly include ulcerative colitis and Crohn disease, is a result of genetic, microbial, and environmental factors. Many genetic loci have been implicated in IBD development in both humans and mouse models. In particular, a gene called Cd14, which encodes the CD14 protein, has been suggested to be a candidate gene for IBD susceptibility.

Liver disease, which includes is more than a hundred different kinds of diseases of the liver, constitutes one of the most common causes of death worldwide. In Australia alone, approximately 6 million people are suffering from liver disease, putting an enormous burden on the health care system. It is imperative to develop more effective therapeutic agents for liver disease.

One type of liver disease, hepatitis, is an inflammation of the liver tissue. It is most frequently caused by viruses, although the condition can also be caused by other factors, such as heavy alcohol use, certain medications, toxins, other infections, and autoimmune diseases. Over time, hepatitis may progress to liver fibrosis, cirrhosis, liver failure, and liver cancer.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease and motor neurone disease (MND), is a fatal disorder of motor neurons. It is the most common adult-onset motor neuron disease and is characterized by progressive paralysis and death. Currently, no treatment substantially slows disease progression. The etiological underpinnings of ALS are complex and not fully understood. A lot of genes have been implicated in ALS, including C9orf72, SOD1, TARDBP, and FUS, which are key to the normal function of motor neurons and other cells.

Now a new study shows that a variant in UBQLN4 gene is associated with ALS. The study, led by Dr Yongchao Ma from Northwestern University Feinberg School of Medicine, reveals that UBQLN4 gene variant disrupts a pathway that drives motor neuron development.

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.