Dantrolene shows promise for treating DMD

 

We know that, Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), 3,4-methylenedioxymethamphetamine ("ecstasy") intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning. It is marketed by JHP Pharmaceuticals LLC as Dantrium (in North America) and Dantrolen (Europe).

  

Dantrolene shows promise for treating DMD

Dantrolene shows promise for treating DMD

 

We know that, Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), 3,4-methylenedioxymethamphetamine   ("ecstasy") intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning. It is marketed by JHP Pharmaceuticals LLC as Dantrium (in North America) and Dantrolen (Europe).

  

Dantrolene shows promise for treating DMD

Lapatinib benefits found for HER2-positive early-stage patients

In continuation of my update on Lapatinib

Lapatinib benefits found for HER2-positive early-stage patients

FDA Approves Varizig for Reducing Chickenpox Symptoms

FDA Approves Varizig for Reducing Chickenpox Symptoms :

Varizag : http://www.cangene.com/VariZIG

Abiraterone improves outcomes for prostate cancer prior to chemo

In continuation of my update on abiraterone

Abiraterone improves outcomes for prostate cancer prior to chemo

Vismodegib team wins Drug Discovery of the Year award

In continuation of my update on Vismodegib

Vismodegib team wins Drug Discovery of the Year award: The British Pharmacological Society proudly announces that its first annual Drug Discovery of the Year award has been won by the discovery team developing vismodegib for the treatment of basal cell carcinoma (a type of skin cancer).

New low-cost combined therapy shows promise against malaria

Molecular parasitologist Stephen Rich at the University of Massachusetts Amherst has led a research team who report a promising new low-cost combined therapy with a much higher chance of outwitting P. falciparum than current modes. He and plant biochemist Pamela Weathers at the Worcester Polytechnic Institute (WPI), with research physician Doug Golenbock at the UMass Medical School, also in Worcester, have designed an approach for treating malaria based on a new use of Artemisia annua, a plant employed for thousands of years in Asia to treat fever.

"The emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed," says UMass Amherst graduate student and lead author Mostafa Elfawal. Rich, an expert in the malaria parasite and how it evolves, adds, "We no sooner get the upper hand than the parasite mutates to become drug resistant again. This cycle of resistance to anti-malarial drugs is one of the great health problems facing the world today. We're hoping that our approach may provide an inexpensive, locally grown and processed option for fighting malaria in the developing world."

Currently the most effective malaria treatment uses purified extracts from the Artemisia plant as part of an Artemisinin Combined Therapy (ACT) regime with other drugs such as doxycycline and/or chloroquine, a prescription far too costly for wide use in the developing world. Also, because Artemisia yields low levels of pure artemisinin, there is a persistent worldwide shortage, they add.

The teams's thesis, first proposed by Weathers of WPI, is that locally grown and dried leaves of the whole plant, rich in hundreds of phytochemicals not contained in the purified drug, might be effective against disease at the same time limiting post-production steps, perhaps substantially reducing treatment cost. She says, "Whole-plant Artemisia has hundreds of compounds, some of them not even known yet. These may outsmart the parasites by delivering a more complex drug than the purified form."

Rich adds, "The plant may be its own complex combination therapy. Because of the combination of parasite-killing substances normally present in the plant (artemisinin and flavonoids), a synergism among these constituent compounds might render whole plant consumption as a form of artemisinin-based combination therapy, or what we're calling a 'pACT,' for plant Artemisinin Combination Therapy."

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052746

New low-cost combined therapy shows promise against malaria

Research | Research news | Fighting sleeping sickness with X-ray lasers

Using the world’s most powerful X-ray free-electron laser, an international team of researchers, including scientists of the Max Planck Institute for Medical Research in Heidelberg, has obtained new insight into the structure of a medicinally important protein that may serve as a blueprint for the development of drugs to fight sleeping sickness. Science magazine have chosen the experimental study as one of the top ten scientific breakthroughs of the year.

Research | Research news | Fighting sleeping sickness with X-ray lasers

Stroke drug kills bacteria that cause ulcers and tuberculosis

Now researchers  found that, a compound called ebselen (see structure) effectively inhibits the thioredoxin reductase system in a wide variety of bacteria, including Helicobacter pylori which causes gastric ulcers and Mycobacterium tuberculosis which causes tuberculosis. Thioredoxin and thioredoxin reductase proteins are essential for bacteria to make new DNA, and protect them against oxidative stress caused by the immune system. Targeting this system with ebselen, and others compounds like it, represents a new approach toward eradicating these bacteria.

Building on previous observations where ebselen has shown antibacterial properties against some bacteria, Holmgren and colleagues hypothesized that the bacteria sensitive to ebselen relied solely on thioredoxin and thioredoxin reductase for essential cellular processes. They investigated this by testing it on strains of E. coli with deletions in the genes for thioredoxin, thioredoxin reductase and the glutaredoxin system. They found that strains with deletions in the genes coding for glutaredoxin system were much more sensitive than normal bacteria. Researchers further tested ebselen againstHelicobacter pylori andMycobacterium tuberculosis, which both naturally lack the glutaredoxin system and are frequently resistant to many commonly used antibiotics, and found both to be sensitive to ebselen.

"As rapidly as these organisms evolve, we need new drugs sooner rather than later," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The fact that these scientists have found a new target for killing some of the most resistant bacteria is great news, but the fact that we already have at least one drug which we could possibly use now makes the news even better."

Ref : http://www.fasebj.org/content/early/2012/12/17/fj.12-223305

Stroke drug kills bacteria that cause ulcers and tuberculosis

New Blood Thinner May Help Prevent Leg Clots, Study Finds - Drugs.com MedNews

In continuation of my update on apixaban....

We know that, Apixaban (BMS-562247-01, tradename Eliquis) is an anticoagulant for the prevention of venous thromboembolism and venous thromboembolic events. It is a direct factor Xa inhibitor. Apixaban has been available in Europe since May 2012 and was approved for preventing venous thromboembolism after elective hip or knee replacement.^[1] An FDA decision on apixaban for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation was expected on June 28, 2012, but was delayed. It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb.

New Blood Thinner May Help Prevent Leg Clots, Study Finds - Drugs.com MedNews

Drug used to treat HIV might defuse deadly staph infections

We know that, Maraviroc (structure below, brand-named Selzentry, or Celsentri outside the U.S.) is an antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. It is also classed as an entry inhibitor. It also appeared to reduce graft-versus-host disease in patients treated with allogeneic bone marrow transplantation for leukemia, in a phase 1/2 study.

Now  researchers from  NYU School of Medicine  suggests that an existing HIV drug called maraviroc could be a potential therapy for Staphylococcus aureus, a notorious and deadly pathogen linked to hundreds of thousands of hospitalizations each year.

The discovery arose from a serendipitous finding that was a part of a collaborative study between Dr. Torres, a bacteriologist, and immunologist Derya Unutmaz, MD, associate professor of microbiology and pathology and medicine, whose laboratories are adjacent to each other. 

They focused on a receptor called CCR5 that dots the surface of immune T cells, macrophages, and dendritic cells. Sixteen years ago, researchers at NYU School of Medicine discovered that CCR5 is the receptor HIV uses to gain entry into T cells in order to replicate, spread, and cause an infection that can progress into AIDS.

That same receptor has now been found to be critical to the ability of certain strains of Staph to specifically target and kill cells with CCR5, which orchestrate an immune response against the bacteria. The scientists discovered that one of the toxins the bacterium releases, called LukED, latches on to CCR5 and subsequently punches holes through the membrane of immune cells, causing them to rapidly die. The LukED toxin belongs to a family of proteins called leukotoxins, encoded and produced by Staph to fight off the immune system's defenses.

Ref : http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11724.html

Drug used to treat HIV might defuse deadly staph infections

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

In continuation of my update on Everolimus

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

Treatment with everolimus led to tumor regression and  gnificantly improved survival compared  with placebo in mice with established lymphomas. However,  all  of  these  mice  eventually  relapsed as a result   of the growth of lymphoma  cells  resistant to the effec ts  of everolimus.

"These data confirmed our hypothesis that mTORC1 inhibition could suppress Myc-driven tumor initiation and growth," said McArthur. "The surprise was found in how mTORC1 inhibition led to tumor regression. We had expected that it would trigger cancer cells to die by a cellular process known as apoptosis, but we found that this was not the case."

Detailed analysis of the tumors indicated that everolimus caused tumor regression by inducing cellular senescence.

According to McArthur, normal cells protect themselves when cancer-driving genes are switched on is by entering a state called senescence. When cancers develop, they have found ways to overcome this safeguard. "Our data indicate that one way in which cancers bypass senescence, in particular senescence induced by Myc, is through a signaling pathway involving mTORC1," he said.

Resistance to everolimus treatment in mice with established lymphomas was associated with loss of the function of p53, a protein known to help suppress tumor formation and growth.

"The loss of effectiveness of everolimus therapy against lymphoma cells deficient in p53 function has important clinical implications," said McArthur. "Everolimus could be a useful new string to the bow for clinicians treating patients with Myc-driven cancers, in particular B cell lymphomas, but that it would be helpful only to those patients with functional p53."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2012/12/13/2159-8290.CD-12-0404.abstract?sid=79f94616-1798-4c19-92c2-26e76ad12905 

Antidepressant could do double duty as diabetes drug, study shows

We know that, Paroxetine (also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin) is an antidepressant drug of the SSRItype. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder and generalized anxiety disorder in adult outpatients.

Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Genericformulations have been available since 2003 when the patent expired.

In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity.  Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Paroxetine is associated with clinically significant weight gain. Pediatric trials of paroxetine for depression did not demonstrate statistical efficacy better than placebo.

Now University of Texas Medical Branch at Galveston researchers have  discovered that the commonly used antidepressant drug paroxetine could also become a therapy for the vascular complications of diabetes...

"The future potential of this study is that we may be able to 'repurpose' paroxetine for the experimental therapy of diabetic cardiac complications," Szabo said. "We'll need to carefully characterize its safety profile in diabetic patients, but I think there's definite potential here."

Ref : http://diabetes.diabetesjournals.org/content/early/2012/12/03/db12-0789
Antidepressant could do double duty as diabetes drug, study shows

Pfizer, Ligand announce FDA acceptance of bazedoxifene/conjugated estrogens NDA

Pfizer Inc.  and Ligand Pharmaceuticals Incorporated recently,  announced that the United States Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) for bazedoxifene/conjugated estrogens (BZA/CE), a potential new medicine for non-hysterectomized women for the treatment of moderate-to-severe vasomotor symptoms (VMS) and vulvar and vaginal atrophy (VVA) associated with menopause, as well as the prevention of postmenopausal osteoporosis. The FDA Prescription Drug User Fee Act (PDUFA) date is October 3, 2013. 

Pfizer, Ligand announce FDA acceptance of bazedoxifene/conjugated estrogens NDA

ETA receptor antagonism reduces novel cardiovascular risk factors in patients with CKD

ETA receptor antagonism reduces novel cardiovascular risk factors in patients with CKD:

Blocking the receptor for proteins that constrict blood vessels reduces markers of heart-related problems in patients with chronic kidney disease (CKD), according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). 

Neeraj Dhaun, MD, PhD (University of Edinburgh, in Scotland) and his colleagues conducted a randomized, double-blind study in 27 patients with CKD to compare the effects of sitaxentan, nifedipine (a blood vessel relaxant), and placebo on kidney function, blood pressure, arterial stiffness, and various heart-related markers. Among the major findings after six weeks of treatment:

• Placebo and nifedipine did not affect three markers of heart-related problems: blood levels of uric acid; blood levels of asymmetric dimethylarginine (ADMA), a blocker of NO production; and urine levels of endothelin-1.
• Sitaxentan (see structure above) treatment led to statistically significant reductions in all three of these markers.
• Sitaxentan reduced proteinuria (an excess excretion of protein in the urine) to a significantly greater extent than nifedipine. Proteinuria is an indicator of kidney dysfunction.
• Nifedpine  (right structure below) and sitaxentan both reduced blood pressure to a similar extent.

"The current study shows, for the first time, that ET_A receptor antagonism selectively lowers novel cardiovascular risk factors in patients with kidney disease independent of blood pressure. These effects were seen in patients already receiving optimal treatment," said Dr. Dhaun. "These findings suggest a potential role for ET_A receptor antagonism in conferring additional longer-term cardiovascular and renal benefits in patients with kidney disease," he added.....