Crizotinib drug effectively halts growth of ROS1-positive lung tumors

In continuation of my update on crizotinib

Treatment with the targeted therapy drug crizotinib effectively halts the growth of lung tumors driven by rearrangements of the ROS1 gene. In an article receiving Online First publication in the New England Journal of Medicine to coincide with a presentation at the European Society for Medical Oncology meeting, an international research team reports that crizotinib treatment led to significant tumor shrinkage in 36 of 50 study participants and suppressed tumor growth in another 9.

"Prior to this study, there were a handful of reports describing marked responses to crizotinib in individual patients with ROS1-positive lung tumors," says Alice Shaw, MD, PhD, of the Massachusetts General Hospital (MGH) Cancer Center, lead author of the NEJM report. "This is the first definitive study to establish crizotinib's activity in a large group of patients with ROS1-positive lung cancer and to confirm that ROS1 is a bona fide therapeutic target in those patients."

Crizotinib currently is FDA-approved to treat non-small-cell lung cancers (NSCLC) driven by rearrangments in the ALK gene, which make up around 4 percent of cases. An MGH Cancer Center report published in 2012 reported that 1 to 2 percent of NSCLCs are driven by rearrangements in ROS1, which encodes a protein with significant structural similarities to that encoded by the ALK gene.

Crizotinib drug effectively halts growth of ROS1-positive lung tumors

FDA Approves Iluvien for Diabetic Macular Edema

pSivida Corp., a leader in the development of sustained release, drug delivery products for treating eye diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved Iluvien for the treatment of diabetic macular edema (DME). It is indicated for patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure (IOP). A single injection of the Iluvien micro-insert provides sustained treatment of DME for 36 months. Approximately 560,000 people in the U.S. are estimated to have clinically significant DME, the most frequent cause of vision loss in individuals with diabetes and the leading cause of blindness in young and middle-aged adults in developed countries. Iluvien is expected to be commercially available in the U.S. in early 2015.

FDA Approves Iluvien for Diabetic Macular Edema

Candidate H7N9 avian flu vaccine works better with adjuvant

Candidate H7N9 avian flu vaccine works better with adjuvant

Researchers Discover How Bacteria Resist Antibiotics in Hospitals

Tiny circles of DNA called plasmids appear to be the culprit. They can easily enter bacteria and move from one bacteria to another, and some carry a gene that makes bacteria drug-resistant, a new study finds.

"The plasmids we are talking about carry an antibiotic-resistant gene to a class of antibiotic called carbapenems," said the study's co-author, Dr. Tara Palmore, an infection control specialist at the U.S. National Institutes of Health.

Carbapenems are antibiotics of last resort, and carbapenem-resistant Enterobacteriaceae (CRE) are bacterial pathogens that pose a "formidable" threat to hospitalized patients, according to the research.

The incidence of CRE has quadrupled in the last decade in the United States, according to background information in the report. CRE has been detected in nearly 4 percent of hospitals and about 18 percent of long-term acute care facilities. In addition, the researchers noted, CRE are resistant to most, if not all, antibiotics. Investigations have reported a death rate of 40 percent to 80 percent from infection.

Given ongoing concerns that even bacteria like Klebsiella and Enterobacter -- which are found in the environment and in healthy stomachs -- are becoming increasingly resistant to last-resort antibiotics, the researchers set out to find some answers. Their report, published Sept. 17 inScience Translational Medicine, showed that plasmid transfer in hospitals is likely contributing to the increase in antibiotic-resistant bacteria.

Researchers Discover How Bacteria Resist Antibiotics in Hospitals

FDA Approves Triumeq for the Treatment of HIV-1 Infection

In continuation of my update on Triumeq

ViiV Healthcare announced today that the U.S. Food and Drug Administration (FDA) has approved Triumeq (abacavir 600mg, dolutegravir 50mg and lamivudine 300mg) tablets for the treatment of HIV-1 infection. Triumeq is ViiV Healthcare’s first dolutegravir-based fixed-dose combination, offering many people living with HIV the option of a single-pill regimen that combines the integrase strand transfer inhibitor (INSTI) dolutegravir, with the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir and lamivudine.

FDA Approves Triumeq for the Treatment of HIV-1 Infection

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

In continuation of my update on bupropion/naltrexone

The U.S. Food and Drug Administration today approved Contrave (naltrexone hydrochloride and bupropion hydrochloride extended-release tablets) as treatment option for chronic weight management in addition to a reduced-calorie diet and physical activity.

FDA Approves Contrave (bupropion/naltrexone) for Weight Management

The Nobel Prize in Physiology or Medicine 2014

The Nobel Prize in Physiology or Medicine 2014

FDA Approves Otezla (apremilast) for Moderate to Severe Plaque Psoriasis

 In continuation of my update on Apremilast (brand name Otezla) is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast specifically inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity.

FDA Approves Otezla (apremilast) for Moderate to Severe Plaque Psoriasis

FDA Approves Spiriva Respimat (tiotropium) for the Maintenance Treatment of COPD

We know that, Tiotropium bromide,   is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium bromide capsules for inhalation are co-promoted by Boehringer-Ingelheimand Pfizer under the trade name Spiriva. It is also manufactured and marketed by Cipla under trade name Tiova.

Now Boehringer Ingelheim Pharmaceuticals, Inc. announced  that the U.S. Food and Drug Administration (FDA) approved Spiriva Respimat (tiotropium bromide) inhalation spray for the long-term, once-daily

FDA Approves Spiriva Respimat (tiotropium) for the Maintenance Treatment of COPD

FDA Approves Vitekta (elvitegravir) for HIV-1 Infection

We know that, Elvitegravir (EVG, formerly GS-9137) is a drug used for the treatment of HIV infection. It acts as an integrase inhibitor. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008.^[2][3][4]The drug gained approval by U.S. Food and Drug Administration on August 27, 2012 for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild.

FDA Approves Vitekta (elvitegravir) for HIV-1 Infection

Scripps Research Institute Chemists Modify Antibiotic to Vanquish Resistant Bacteria

Scientists at The Scripps Research Institute (TSRI) have devised a new antibiotic based on vancomycin that is powerfully effective against vancomycin-resistant strains of MRSA and other disease-causing bacteria.

The new vancomycin analog appears to have not one but two distinct mechanisms of anti-microbial action, against which bacteria probably cannot evolve resistance quickly.

“This is the prototype of analogues that once introduced will still be in clinical use a generation or maybe even two generations from now,” said Dale L. Boger, the Richard and Alice Cramer Professor of Chemistry at TSRI.

The report by Boger and members of his laboratory was published recently online ahead of print by the Journal of the American Chemical Society.

Increasing Reports of Resistance

Vancomycin entered clinical use in 1958, five years after its isolation from microbes in a soil sample gathered by an American missionary in Borneo. For nearly six decades it has been useful against a wide range of bacteria, and it remains a standard weapon against methicillin-resistant Staphylococcus aureus (MRSA), a major cause of hospital-acquired infections. A compound closely related to vancomycin also has been widely used to protect livestock.

Since the late 1980s, there have been increasing reports of vancomycin resistance in classes of bacteria that usually succumb to the antibiotic, including MRSA. Although vancomycin remains useful, scientists have been looking for new drugs to replace it in cases—often life-threatening—where it no longer can help patients.

The Boger laboratory has focused on inventing improved versions of vancomycin rather than entirely new compounds. “Vancomycin has lasted in clinical use for more than 50 years, in part because it isn’t very vulnerable to antibiotic resistance,” Boger said. “Our thought has been that if we find a vancomycin analog that addresses this current source of resistance we’ll get another 50 years of use out of it.”

Vancomycin works by binding to the building blocks of bacterial cell walls, in a way that prevents their proper assembly and leaves bacteria too leaky to live and replicate. The resistance comes from a single amino-acid alteration that some bacteria make to those building blocks, so that the antibiotic molecule can no longer get a firm grip. That drops vancomycin’s potency by a factor of about 1,000.

‘Incredibly Potent’

In 2012, Boger and his team reported making a vancomycin analog—informally termed vancomycin amidine—with a subtly altered binding pocket that fastens about equally well to the original and resistant sites on bacterial cell wall subunits. To get the precise structural modification they needed, they had to come up with a method for the “total synthesis” of this vancomycin-based compound—a controlled, step-by-step construction using organic chemistry reactions in the lab, rather than a natural enzyme-mediated production within cells.

“Years of work in this lab culminated in a total synthesis strategy that not only allowed us access to this target compound, but also gave us the ability to perform almost any other chemical modification of vancomycin that we wished,” said Akinori Okano, first author of the new report, who is an assistant professor of chemistry at TSRI.

Vancomycin amidine turned out to have acceptable level of activity against vancomycin-resistant and -sensitive bacteria, yet there was room for improvement. Thus in the new study, Okano, Boger and their colleagues used their vancomycin synthesis methods to add an additional feature to the molecule—a peripheral chlorobiphenyl (CBP), long known as a general booster of vancomycin’s potency.

“To our delight, the combination of these modifications led to an incredibly potent molecule, well beyond anything we had expected,” said Okano.

Scripps Research Institute Chemists Modify Antibiotic to Vanquish Resistant Bacteria

FDA Approves Tybost (cobicistat) for use in the treatment of HIV-1 Infection

We know that, Cobicistat (formerly GS-9350) is a licensed drug for use in the treatment of infection with the human immunodeficiency virus (HIV).

Like ritonavir (Norvir), cobicistat is of interest for its ability to inhibit liver enzymes that metabolize other medications used to treat HIV, notably elvitegravir, an HIV integrase inhibitor. By combining cobicistat with elvitegravir, higher concentrations of the latter are achieved in the body with lower dosing, theoretically enhancing elvitegravir's viral suppression while diminishing its adverse side-effects. In contrast with ritonavir, the only other booster approved for use as a part of HAART, cobicistat has no anti-HIV activity of its own.. 

 Now U.S. Food and Drug Administration (FDA) has approved Tybost (cobicistat), a CYP3A inhibitor used in combination with atazanavir or darunavir for the treatment of human immunodeficiency virus type 1 (HIV-1) infection..

FDA Approves Tybost (cobicistat) for use in the treatment of HIV-1 Infection

Bacterial communication molecules can be manipulated to prevent cancer cells from spreading

Bacterial communication molecules can be manipulated to prevent cancer cells from spreading

Rosuvastatin promotes bone growth in mice with achondroplasia symptoms

Skeletal dysplasia is a group of rare diseases that afflict skeletal growth through abnormalities in bone and cartilage. Its onset hits at the fetal stage and is caused by genetic mutations. A mutation in the gene encoding fibroblast growth factor receptor 3 (FGFR3) has been associated with two types of skeletal dysplasia, thanatophoric dysplasia (TD), a skeletal dysplasia that cause serious respiratory problems at birth and is often lethal, and achondroplasia (ACH), which causes stunted growth and other complications throughout life. Several experimental treatments have been considered, but none are commercially available.

The need for new drug compounds that can combat skeletal dysplasia has led the Noriyuki Tsumaki group at CiRA, Kyoto University, to consider iPS cell technology. In a joint study with Associate Professor Hideaki Sawai of Hyogo College of Medicine and Team Leader Shiro Ikegawa of RIKEN, Professor Tsumaki's team screened molecules based on their ability to rescue TD-iPSCs from degraded cartilage. Molecules known to affect FGFR3 signaling and/or the metabolism of chondrocytes, the cells responsible for growing cartilage, were identified as good candidates. More importantly, so too were statins, a class of drugs renown for their action against cholesterol and investigated because they have anabolic and protective effects on chondrocytes.

The authors used iPS cells generated from the fibroblasts of both healthy individuals (WT-iPSC) and TD patients (TD-iPSC). Chondrocytes differentiated from TD-iPSC produced less cartilage than those from WT-iPSC and also had a lower proliferation rate and greater apoptosis, properties that were attributed to a gain of function by the mutated FGFR3. Adding statin recovered the cartilage formation in TD-iPSC and increased the proliferation rate. Coincidently, the group observed increased expressions of SOX9, a chondrocytic transcription factor, and of COL2A1 and ACAN, two cartilage extracellular components, all of which are down-regulated in TD patients. Moreover, statin treatment was found to accelerate the degradation of the FGFR3 protein in chondrogenically differentiated TD-iPSC, a process inhibited in TD cases.

Read more at :https://www.cira.kyoto-u.ac.jp/e/pressrelease/news/140918-110738.html

Rosuvastatin promotes bone growth in mice with achondroplasia symptoms

FDA Approves Cerdelga (eliglustat) for Type 1 Gaucher Disease

The U.S. Food and Drug Administration today approved Cerdelga (eliglustat) for the long-term treatment of adult patients with the Type 1 form of Gaucher disease, a rare genetic disorder.

Gaucher disease occurs in people who do not produce enough of an enzyme called glucocerebrosidase. The enzyme deficiency causes fatty materials to collect in the spleen, liver and bone marrow. The major signs of Gaucher disease include liver and spleen enlargement, low red blood cell counts (anemia), low blood platelet counts and bone problems.

Cerdelga is a hard gelatin capsule containing eliglustat that is taken orally. In patients with Gaucher disease Type 1, the drug slows down the production of the fatty materials by inhibiting the metabolic process that forms them. Type 1 Gaucher disease is estimated to affect about 6,000 people in the United States.

FDA Approves Cerdelga (eliglustat) for Type 1 Gaucher Disease