Journal of Drugs in Dermatology publishes findings on new injectable drug ATX-101

In continuation of my update on ATX-101    .......

Double chins are clinically defined by accumulation of subcutaneous fat in the submental area. The result? A double chin that impacts perceptions of facial attractiveness. In "A Phase I Safety and Pharmacokinetic Study of ATX-101: Injectable, Synthetic Deoxycholic Acid for Submental Contouring," Patricia Walker MD PhD, Jere Fellmann PhD, and Paul F. Lizzul MD PhD MBA MPH explain how ATX-101 (deoxycholic acid [DCA] injection) has the potential to provide a less invasive alternative for submental fat reduction and contouring. Both in vivo and in vitro studies show that, when injected into submental subcutaneous fat tissue, ATX-101 results in the targeted destruction of fat cells. The data support favorable safety and efficacy observations. Adverse events were bruising and swelling associated with the treatment area that are mild or moderate in severity. FDA approval for use of ATX-101 above the chest is expected in May 2015.

Journal of Drugs in Dermatology publishes findings on new injectable drug ATX-101

Low doses of imatinib drug can push immune system to combat bacterial infections

In contiuation of my update on Imatinib

Low doses of the anti-cancer drug imatinib can spur the bone marrow to produce more innate immune cells to fight against bacterial infections, Emory researchers have found.

The results were published March 30, 2015 in the journal PLOS Pathogens.

The findings suggest imatinib, known commercially as Gleevec , or related drugs could help doctors treat a wide variety of infections, including those that are resistant to antibiotics, or in patients who have weakened immune systems. The research was performed in mice and on human bone marrow cells in vitro, but provides information on how to dose imatinib for new clinical applications.

"We think that low doses of imatinib are mimicking 'emergency hematopoiesis,' a normal early response to infection," says senior author Daniel Kalman, PhD, professor of pathology and laboratory medicine at Emory University School of Medicine.

Ref : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004770

Low doses of imatinib drug can push immune system to combat bacterial infections

Old leukemia drug may help in fight against cancer

A drug used for decades to treat leukemia may have other uses in the fight against cancer, researchers at the University of Missouri have found. Previously, doctors used 6-Thioguanine, or 6-TG, as a chemotherapy treatment to kill cancer cells in patients with leukemia.

Old leukemia drug may help in fight against cancer

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Pharmalink AB, a specialty pharma company, announces that it has acquired a novel product candidate in development for treating inflammation from Synartro AB. No financial details are disclosed.

The product candidate, which consists of an anti-inflammatory drug conjugated to a biopolymer, has been developed using Synartro's drug delivery technology to create locally acting pharmaceuticals with limited systemic exposure. Pharmalink intends to develop the product for osteoarthritis, an indication where it has demonstrated promising results in pre-clinical studies. Pharmalink will apply its formulation and clinical development expertise to advance the candidate product through clinical trials towards market.

 

Pharmalink has extensive experience in developing locally delivered anti-inflammatory drugs with limited systemic uptake. Its most advanced product is Nefecon®, (a new oral formulation of the glucocorticosteroid, budesonide above structures respectively), modified-release capsule of the corticosteroid, budesonide, in Phase 2b clinical development for treating patients with IgA nephropathy at risk of developing end-stage renal disease, despite optimized standard-of-care therapy.

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Novel molecule inhibits cancer-causing transcription factors

A novel molecule designed by scientists at the University of Massachusetts Medical School and the University of Virginia inhibits progression of a hard-to-treat form of recurring acute myeloid leukemia (AML) in patient tissue. The small molecule is one of the first designed to specifically target a cancer-causing transcription factor. Previously thought to be an undruggable target, this strategy may be used to design other novel molecules that can specifically inhibit cancer-causing transcription factors. Details of the work were published in Science.

Transcription factors are single- or multi-protein complexes that regulate transcription of DNA into messenger RNA and gene expression by binding to regions on the genome next to a gene. Mutations in transcription factors can result in altered gene expression programs that give way to new, cancer-causing functions. Although these aberrant transcription factors are promising targets for new therapeutics, the complexity of interrupting very specific protein-to-protein interactions has made it difficult to find small molecules or design drugs that treat these cancers.

"When we look at inhibitors, they usually target an enzyme or receptor. There aren't a lot of good examples of transcription factor inhibitors in clinical trials," said Lucio H. Castilla, PhD, associate professor of molecular, cell and cancer biology and co-leader of the study. "Here, we've used our extensive knowledge of a mutant transcription factor found in a subset for acute myeloid leukemia patients to design a molecule that can specifically sequester only the oncogenic mutant. This leaves the normal transcription factor to bind to the DNA and restore gene expression.".......

Ref : http://www.sciencemag.org/content/347/6223/779.abstract?sid=73b04258-783e-43e4-8e1d-09fe5eb7d331

Novel molecule inhibits cancer-causing transcription factors

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

Pharmalink AB, a specialty pharma company, announces that it has acquired a novel product candidate in development for treating inflammation from Synartro AB. No financial details are disclosed.

The product candidate, which consists of an anti-inflammatory drug conjugated to a biopolymer, has been developed using Synartro's drug delivery technology to create locally acting pharmaceuticals with limited systemic exposure. Pharmalink intends to develop the product for osteoarthritis, an indication where it has demonstrated promising results in pre-clinical studies. Pharmalink will apply its formulation and clinical development expertise to advance the candidate product through clinical trials towards market.

 

Pharmalink has extensive experience in developing locally delivered anti-inflammatory drugs with limited systemic uptake. Its most advanced product is Nefecon®, (a new oral formulation of the glucocorticosteroid, budesonide above structures respectively), modified-release capsule of the corticosteroid, budesonide, in Phase 2b clinical development for treating patients with IgA nephropathy at risk of developing end-stage renal disease, despite optimized standard-of-care therapy.

Pharmalink AB acquires anti-inflammatory drug candidate from Synartro AB

GFT505 demonstrates dose-dependent efficacy on primary endpoint in phase 2 NASH trial

GENFIT (Euronext: GNFT; ISIN: FR0004163111), today announces topline results of the phase 2 GOLDEN-505 trial in NASH.

Due to the unexpected rate of resolution of NASH in patients randomized to placebo who had early NASH (NAS of 3, placebo response rate>57%), along with the high number of sites for a limited sample size, the study as initially designed did not enable the trial to meet directly the primary endpoint. With correction for this baseline severity and site heterogeneity by a standardized statistical analysis, GFT505 120mg meets the primary endpoint: Reversal on NASH without worsening of fibrosis, as detailed below.

Treatment with GFT505 provides a significant beneficial effect on the primary endpoint (GFT505 120mg vs placebo, p=0.016, RR=2.03) in the global randomized population (n=274, full analysis set), where patients without an end of treatment biopsy were considered as non-responders. The primary endpoint was also achieved in the evaluable population of patients who underwent both baseline and end of study liver biopsies (n=237, ITT; p=0.027 vs placebo; RR=1.94). In the evaluable patient population, GFT505 120mg also has a beneficial effect of a decrease of NAS-score ≥2 (p=0.04 vs placebo).

Early NASH patients with NAS=3 were not included in other recent NASH trials. If the same is done in the GOLDEN-505 study, keeping patients with more severe disease defined by NAS≥4 (n=202), GFT505 120mg demonstrates a doubling of responders on the primary endpoint (22.4% vs 12.7%, p=0.046, RR=1.9), thus providing evidence of a clinically meaningful benefit in patients with more advanced disease.

GFT505 demonstrates dose-dependent efficacy on primary endpoint in phase 2 NASH trial

Anti-diabetic medication activates brain sensors, promotes weight gain

Medication used to treat patients with type II diabetes activates sensors on brain cells that increase hunger, causing people taking this drug to gain more body fat, according to researchers at Georgia State University, Oregon Health and Science University, Georgia Regents University and Charlie Norwood Veterans Administration Medical Center.

The study, published on March 18 in The Journal of Neuroscience, describes a new way to affect hunger in the brain and helps to explain why people taking a class of drugs for type II diabetes gain more body fat.

Type II diabetes, the most common form of diabetes, affects 95 percent of diabetes sufferers. People with type I or type II diabetes have too much glucose, or sugar, in their blood. Type II diabetes develops most often in middle-aged and older adults and people who are overweight and inactive, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

The research team found that sensors in the brain that detect free circulating energy and help use sugars are located on brain cells that control eating behavior. This is important because many people with type II diabetes are taking antidiabetics, known as thiazolidinediones (TZDs), which specifically activate these sensors, said Johnny Garretson, study author and doctoral student in the Neuroscience Institute and Center for Obesity Reversal at Georgia State.

The study found peroxisome proliferator-activated receptor ϒ (PPARϒ) sensors on hunger-stimulating cells, known as agouti-related protein (AgRP) cells, at the base of the brain in the hypothalamus. Activating these PPARϒ sensors triggers food hoarding, food intake and the production of more AgRP. When AgRP cells are activated, animals become immediately hungry. These cells are so potent they will wake a rodent up from slumber to go eat, Garretson said.

TZDs help to treat insulin resistance, in which the body doesn't use insulin the way that it should. They help the body's insulin work properly, making blood glucose levels stay on target and allowing cells to get the energy they need, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

Anti-diabetic medication activates brain sensors, promotes weight gain

Promising drug a 'new paradigm' for treating leukemia

Researchers at the University of Virginia School of Medicine have developed a compound that delays leukemia in mice and effectively kills leukemia cells in human tissue samples, raising hopes that the drug could lead to improved treatments in people. The researchers call it an exciting "new paradigm" for treating leukemia.

The compound works by disabling an altered cellular protein that drives one type of acute myeloid leukemia, the most common form of adult leukemia. By blocking that protein, the drug allows a cancerous cell to detect that it has problems and die, rather than continue to grow and spread. In essence, the compound blocks the cellular machinery that the cancer has highjacked.

"This drug that we've developed is ... targeting a class of proteins that hasn't been targeted for drug development very much in the past. It's really a new paradigm, a new approach to try to treat these diseases," said researcher John H. Bushweller, PhD, of the UVA Department of Molecular Physiology and Biological Physics. "This class of proteins is very important for determining how much of many other proteins are made, so it's a unique way of changing the way the cell behaves."

The drug is notable because of its specificity, killing cancerous cells but not healthy cells. "It's what we call a targeted agent. It hits one specific protein," Bushweller said. "It's not a killer of many other types of cells. As far as we can tell, it only really kills the leukemia cells that have this particular altered protein in them."

Ref : http://www.sciencemag.org/content/347/6223/779

Promising drug a 'new paradigm' for treating leukemia  

Common bacteria on verge of becoming antibiotic-resistant superbugs

Antibiotic resistance is poised to spread globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings, according to new research at Washington University School of Medicine in St. Louis.

The study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections.

Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections have been linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.

"Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works," said senior author Gautam Dantas, PhD, associate professor of pathology and immunology. "Given what we know now, I don't think it's overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective."

Dantas and other experts recommend strictly limiting the usage of carbapenems to cases in which no other treatments can help.

The study, conducted by researchers at Washington University, Barnes-Jewish Hospital and the National University of Sciences and Technology in Pakistan, is available online in Emerging Infectious Diseases.

The researchers studied a family of bacteria called Enterobacteriaceae, which includes E. coli, Klebsiella pneumoniae and Enterobacter. Some strains of these bacteria do not cause illness and can help keep the body healthy. But in people with weakened immune systems, infections with carbapenem-resistant versions of these bacteria can be deadly.

Common bacteria on verge of becoming antibiotic-resistant superbugs 

New drug fails to prevent irreversible injury to the heart after angioplasty

Patients who received the new drug Bendavia before undergoing angioplasty or receiving a stent to clear blocked arteries after a heart attack showed no significant reduction in scarring as compared to patients given a placebo, according to a study presented at the American College of Cardiology's 64th Annual Scientific Session.

The study is the first randomized, controlled trial of Bendavia, a drug designed to reduce the extent of tissue damage in the heart through a new approach that targets mitochondria in the cells. Although patients receiving the drug showed a 10 percent reduction in scarring during the first three days after surgery as measured by the levels of an enzyme called creatinine kinase-MB, the study's primary endpoint, the difference was not statistically significant. The results also suggested a trend toward improved heart pumping function during the eight hours following the drug's administration, but that trend also did not reach statistical significance.

New drug fails to prevent irreversible injury to the heart after angioplasty

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

New animal studies at Henry Ford Hospital found that sildenafil, a drug commonly used to treat erectile dysfunction, may be effective in relieving painful and potentially life-threatening nerve damage in men with long-term diabetes.   

The research targeted diabetic peripheral neuropathy, the most common complication of diabetes, affecting as many as 70 percent of patients.

The study was recently published online in PLOS ONE. Lei Wang, M.D., the Henry Ford neuroscientist who led the research, said that although numerous drugs have been shown to be effective in earlier animal experiments, most have not provided benefits in clinical trials.

"Generally, young diabetic animals with an early stage of peripheral neuropathy are used to investigate various drug treatments," Dr. Wang explains. "But patients with diabetes who are enrolled in clinical trials often are older and have advanced peripheral neuropathy.

"Failure to develop and properly evaluate treatments in the laboratory that properly reflect the target clinical population with diabetic peripheral neuropathy may contribute to the failure of clinical trials."

To mimic clinical trials in which diabetes patients have advanced peripheral neuropathy, the Henry Ford researchers chose male mice with type II diabetes that were 36 weeks old, roughly equivalent to middle age in humans.

Sildenafil drug may effectively relieve nerve damage in men with long-term diabetes

FDA approves CHOLBAM (cholic acid) for treatment of bile acid synthesis disorders

         

Asklepion Pharmaceuticals, LLC. today announced that the U.S. Food and Drug Administration (FDA) approved CHOLBAM™ (cholic acid) as a once-daily treatment for cholic acid deficiency in bile acid synthesis disorders due to single enzyme defects. This indication is based on CHOLBAM's ability to markedly improve or normalize liver function test values and to improve general health, as measured by weight gain. CHOLBAM was also approved as an adjunct to standard of care for peroxisomal disorders including Zellweger spectrum disorders in patients with evidence of liver disease, based on improvements in liver function.

CHOLBAM is the first medication approved by the FDA to turn off a genetically-damaged bile synthesis pathway and prevent its toxic products from damaging the liver. The approval of CHOLBAM is a testament to the pioneering work of Dr. Kenneth Setchell and Dr. James Heubi of Cincinnati Children's Hospital and Medical Center, who were the first to recognize many of the constituent diseases and develop a safe and effective therapy. The U.S. approval of CHOLBAM was based on two pivotal trials that showed improved liver function test values and restoration of growth assessed by weight gain in comparison to the natural history of untreated patients. Some patients in these trials have been healthy on therapy, exhibiting normal liver function for more than 16 years.

FDA approves CHOLBAM (cholic acid) for treatment of bile acid synthesis disorders

CASI initiates ENMD-2076 Phase 2 trial in Chinese patients with triple-negative breast cancer

       

CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company dedicated to the acquisition, development and commercialization of innovative therapeutics addressing cancer and other unmet medical needs for the global market with a commercial focus on China, announces that it has initiated a Phase 2 trial of its target therapy drug candidate ENMD-2076 in triple-negative breast cancer (TNBC) at the Cancer Hospital of Chinese Academy of Medical Sciences in Beijing, China. Binghe Xu, MD, Ph.D., Professor and Director of the Department of Medical Oncology at the Cancer Hospital of Chinese Academy of Medical Sciences is the principal investigator of the trial.

CASI initiates ENMD-2076 Phase 2 trial in Chinese patients with triple-negative breast cancer

Existing drugs could help prevent deadly familial stomach and lobular breast cancers

Deadly familial stomach and lobular breast cancers could be successfully treated at their earliest stages, or even prevented, by existing drugs that have been newly identified by cancer genetics researchers at New Zealand's University of Otago.

The researchers, led by Professor Parry Guilford, show for the first time that the key genetic mutation underlying the devastating conditions also opens them to attack through drug therapies targeting other cellular mechanisms.

There is currently no treatment for this kind of gastric cancer other than surgical removal of the stomach as a preventive measure in those identified as carrying the mutated gene. Lobular breast cancer is hard to detect by mammography and mastectomies are also undertaken by some carriers.

The researchers' findings appear in the US journal Molecular Cancer Therapeutics.

The team used genomic screening to search for vulnerabilities in the cancer cells that lack the tumour-suppressor protein E-cadherin. The genetic mutation that causes this protein to be lost is common in hereditary diffuse gastric and lobular breast cancers.

E-cadherin is not a traditional drug target for these forms of cancer because the protein is present in healthy cells but absent in malignant ones. However, Professor Guilford and his team predicted that its loss might create other vulnerabilities in these cancer cells. 

Professor Guilford says the research team used an approach of searching for 'synthetically lethal' combinations of E-cadherin loss with inactivation of other proteins, which together cause cell death.

 (Saracatinib)   (Crizotinib)

 (Crizotinib)     (Alisertib)

(Gandotinib)

Existing drugs could help prevent deadly familial stomach and lobular breast cancers