Lovastatin: A New Weapon Against Plague?

We know that, Lovastatin is a member of the drug class of statins,  used for lowering  cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms  and red yeast rice.

Now scientists at the Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (CNRS/Université Aix-Marseille 2), have found that Lovastatin protects animals against the deadly effects of plague.

After inoculating small rodents with the Yersinia pestis bacterium, the team led by Didier Raoult and Michel Drancourt at the URMITE (CNRS/Université Aix-Marseille 2) showed that animals treated with lovastatin presented fewer and less severe infections. Lovastatin therefore has preventive properties against plague mortality in an animal model. This experimental study also reveals that this statin has no direct antibiotic effect against Yersinia pestis but that it prevents the development of septicemia.  

Researchers conclude that Lovastatin had no in-vitro antibiotic effect against Y. pestis. The difference in the mortality between control mice (11/15; 73.5%) and lovastatin-treated mice (3/15; 20%) was significant (P<0.004; Mantel-Haenszel test). Dead mice exhibited Y. pestis septicemia and inflammatory destruction of lung and spleen tissues not seen in lovastatin-treated surviving mice. These data suggest that lovastatin may help prevent the deadly effects of plague, with a caution that field observations are warranted to assess the role of lovastatin in the prophylaxis of human plague....

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010928

FDA accepts Orexigen's Contrave NDA for treatment of obesity

Orexigen Therapeutics, Inc., a biopharmaceutical company focused on the treatment of obesity, recently anounced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company's New Drug Application (NDA) for Contrave(R) (see structrures below ; naltrexone SR   and bupropion SR), its investigational drug for the treatment of obesity. The NDA is based on a substantial body of evidence gathered through the Contrave Obesity Research (COR) clinical program, which included over 4,500 patients.....

"We are pleased the FDA has accepted our NDA for filing and look forward to working with the Agency during the review process," said Michael Narachi, President and CEO of Orexigen. "If approved, we believe Contrave will become an important therapeutic option for obese patients, making weight loss and weight maintenance an achievable cornerstone in the treatment of obesity and its common co-morbidities."

Ref : http://ir.orexigen.com/phoenix.zhtml?c=207034&p=irol-newsArticle&ID=1432740&highlight=

ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer

ACT Biotech's Telatinib receives orphan drug designation from FDA for treatment of gastric cancer..

Telatinib (see structure,  source : ChemBlink) :
(17-Demethoxy-17-allylaminogeldanamycin; Tanespimycin; 17-Allylaminogeldanamycin)

Bone drug (Zoledronic acid) suppresses wandering tumor cells in breast cancer patients

In continuation of my update on zoledronic acid, I find this info really  interesting.  Researchers from Washington University School of Medicine in St. Louis, have found that the bone-strengthening drug zoledronic acid (Zometa) can help fight metastatic breast cancer when given before surgery.

When the drug was given along with chemotherapy for three months before breast cancer surgery, it reduced the number of women who had tumor cells in their bone marrow at the time of surgery.

Tumors shed thousands of cells, which spread throughout the body and are referred to as disseminated tumor cells (DTCs). Breast cancer DTCs often lodge in bone marrow where bone growth factors help them survive.

Chemotherapy can increase bone turnover and bone growth factors, potentially exacerbating the problem of DTCs in the bone, which can resurface later to cause metastatic disease in cancer patients.

Researchers believe that zoledronic acid inhibits the release of growth factors that help support the growth of DTCs.

In this randomized phase II clinical trial, researchers split 109 women with newly diagnosed stage II or stage III breast cancer into two groups. The control group received chemotherapy alone, while the other received a combination treatment of chemotherapy and zoledronic acid. After three months of therapy, patients with DTCs in their bone marrow decreased from 43 percent to 30 percent in the combination group, compared with a decrease from 48 percent to 47 percent in the control group. This result approached statistical significance.

Zoledronic acid treatment with chemotherapy had additional benefits. Women in the combination group experienced significant gains in bone density after 12 months. This is helpful for breast cancer patients, who often develop osteoporosis as a side effect of chemotherapy and other breast cancer treatments.  

The study also suggested that zoledronic acid may help fight certain types of breast tumors directly. Aft speculates that the drug may stop the tumor from making its own blood supply, modify the immune system in a way that makes it harder for tumor cells to survive or even cause the cancer cells to commit suicide.....

Ref : http://www.ncbi.nlm.nih.gov/pubmed/20362507?dopt=Abstract

Chili peppers may cause weight loss and fight fat buildup, says study

In one of my earlier blog article, titled "Peppers may increase energy expenditure in people tying to lose weight"....have mentioned that researchers form UCLA's Center for Human Nutrition in Los Angeles, CA, lead by Dr. David Heber claimed that "peppers may increase energy expenditure in people tying to lose weight". 

Now interestingly, Steven C. Powell, has come up with new evidence that capsaicin (see below structure), the stuff that gives chili peppers their kick, may cause weight loss and fight fat buildup by triggering certain beneficial protein changes in the body. Their study, which could lead to new treatments for obesity, appears in ACS' monthly Journal of Proteome Research........details ...

Ref : Chili peppers may cause weight loss and fight fat buildup, says study  

RADIANT-3 study results show everolimus significantly extends progression-free survival in patients with advanced pancreatic neuroendocrine tumors...

We know that Everolimus (RAD-001, marketed by Novartis under the  tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine and Afinitor in oncology) is the 42-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an mTOR (mammalian target of rapamycin) inhibitor. It is currently used as an immunosuppressant to prevent rejection of organ transplants. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.

The FDA has approved everolimus for the treatment of advanced kidney cancer on March 30, 2009 and for organ rejection prophylaxis on April 22, 2010. Now Novartis Pharmaceuticals Corporation announced that the  Phase III study of Afinitor® (everolimus, see structure) tablets plus best supportive care met its primary endpoint, showing the drug significantly extended progression-free survival, or time without tumor growth, in patients with advanced pancreatic neuroendocrine tumors (NET). The study, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors), is part of the largest clinical trial program of its kind. 

Everolimus is approved under the trade name Afinitor® (everolimus) tablets for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.  

As  per the claim by   Herve Hoppenot, President, Novartis Oncology, Everolimus was developed to inhibit the mTOR protein, which is a critical target in treating various cancers, including NET. Results from RADIANT-3 demonstrate that everolimus has the potential to become an important treatment option for patients with advanced pancreatic NET, where there is a major unmet need.

"These study results will serve as the basis of worldwide regulatory filings for everolimus and bring us one step closer to our goal of offering these patients a new therapy."...says Herve Hoppenot...

Ref : http://www.novartis.com/newsroom/media-releases/en/2010/1421290.shtml

Synthetic peptide may regenerate brain tissue in stroke victims

A synthetic version of a naturally occurring peptide promoted the   creation of new blood vessels and repaired damaged nerve cells in lab animals, according to researchers lead by Dr. Daniel Morris Sr.Staff Physician at Henry Ford Hospital in Detroit.

"Neurorestorative therapy is the next frontier in the treatment of stroke." claims Dr. Daniel Morris...

As per the claim by the researchers,  addition of  the synthetic peptide Thymosin beta 4 (structure : acetate of Thymosin beta 4 : courtesy : ChemBlink) to a group of drug treatments including statins (used for neurorestorative therapy to activate repair mechanisms) repaired and regenerated stroke-injured brain tissue.

Interestingly, this  research follows an earlier study reported by the same team in March, which found that Thymosin beta 4 improved neurological function after stroke in adult rats by increasing the formation of protective myelin around nerve fibers in brain cells.

In the latest study, adult rats were dosed with Thymosin beta 4 one day after they were subjected to a blockage in the cerebral artery, then given four more doses, once every three days. Rats treated only with saline were used as a control group. After eight weeks, the Thymosin beta 4 group showed significant overall improvement compared to the control group.

The researchers concluded that the peptide improved blood vessel density as well as promoted a certain type of immature brain cells called oligodendrocyte progenitor cells to differentiate into mature oligodendrocytes, which produces myelin to protect axons in nerve cells.

These experiments conclude that the peptide repairs and regenerates stroke-injured brain tissue. and as per the claim by the researchers,  the results of the first study also were similar to other research using the peptide to regenerate damaged heart, corneal tissue and wound repair...

Ref : http://www.henryfordhealth.org/body.cfm?id=46335&action=detail&ref=1107

Body's own proteins may lead the way in global fight against tuberculosis

Body's own proteins may lead the way in global fight against tuberculosis

Bafetinib demonstrates significant inhibition of glioblastoma multiforme cell lines (preclinical trials)..

The treatment of chronic myeloid leukemia (CML)  changed  dramatically with the emergence of the ABL tyrosine kinase inhibitor (TKI) imatinib mesilate. However, primary and secondary imatinib resistance has been frequently reported, particularly in patients with advanced-stage disease. To override imatinib resistance, three second-generation ABL TKIs, i.e., dasatinib, nilotinib and bosutinib, were developed. Bafetinib (see structure source : Chemblink :INNO-406, NS-187) is a dual ABL/Lyn inhibitor developed by the team at Kyoto University Hospital in collaboration with Nippon Shinyaku. 

Bafetinib was 25-55 times more potent than imatinib in blocking BCR/ABL autophosphorylation, while otherwise retaining specificity for ABL and Lyn. Bafetinib had antiproliferative effects against cells bearing wild-type or most mutated BCR/ABL proteins, except T315I, and also inhibited BCR/ABL-positive leukemic cell growth in the central nervous system. A phase I study on bafetinib was completed and the agent was well tolerated and demonstrated clinical activity across a range of doses. Responses occurred even in the setting of a heavily pretreated population, thus making bafetinib a viable option for CML therapy.

Recently  CytRx Corporation, announced that its drug candidate bafetinib (formerly known as INNO-406) demonstrated statistically significant inhibition of glioblastoma multiforme cell lines in a preclinical trial. The company believe that bafetinib could be efficacious in several hematological cancers and  it is  preparing to begin evaluating bafetinib in a Phase 2 proof-of-concept clinical trial in high-risk B-cell chronic lymphocytic leukemia (B-CLL) this quarter, as well as a Phase 2 clinical trial in advanced prostate cancer next quarter.... 

Ref : http://www.cytrx.com/inno_406.html

Promising treatment for aggressive lymphoma identified in new study

In continuation of my update on Lenalidomide... I found this info interesting to share with...

Promising treatment for aggressive lymphoma identified in new study

Plectasin - a new weapon against highly resistant microbes ?..

We know that Plectasin, found in Pseudoplectania nigrella (see picture), is the first defensin to  be isolated from a fungus. Plectasin has a chemical structure resembling defensins found in spiders, scorpions, dragonflies and mussels. In laboratory tests, Plectasin was especially active in inhibiting the growth of the common human pathogen Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin has a low toxicity in mice, and cured them of peritonitis and pneumonia caused by S. pneumoniae as efficiently as vancomycin and penicillin, suggesting that it may have therapeutic potentia.

Now researchers lead by Prof. Dr. Hans-Georg Sahl of   Universities of Bonn, Utrecht, Aalborg and of the Danish company Novozymes AS have shed light on how the substance Plectasin,  destroy highly resistant bacteria. As per the claim by the researchers Plectasin binds to a cell-wall building block called lipid II and thus prevents it from being incorporated and thus disrupting the forming of the cell wall in bacteria so that the pathogens can no longer divide. 

In this process, plectasin behaves like a thief which steals the stones off a mason. 'It binds to a cell-wall building block called lipid II and thus prevents it from being incorporated ,' Professor Sahl explains. 'However, bacteria cannot live without a cell wall.' It comes as no surprise that the most famous antibiotic penicillin also inhibits cell-wall synthesis...

Researchers claims that, plectasin is more similar in its mode of action to another widely used drug, vancomycin. Vancomycin had been the drug of choice in combating MRSA strains since the 1980s. Meanwhile, though, there are more and more bacteria that are also resistant to vancomycin. 'However, these strains are still susceptible to plectasin,' Dr. Tanja Schneider emphasises. Nevertheless, there is no permanent solution to the resistance problem even with a new antibiotic . 'It is always just a question of time until the pathogens mutate and become insensitive ,' she says. 'It's a never ending arms race..' authors conclude that plectasin will be promising lead compound for new antibiotics...

Ref : http://www.sciencemag.org/cgi/content/abstract/328/5982/1168

Healthcare associated infection prevention....

Idiom "prevention is better than cure" is  more relevant than ever, but the awareness is lacking in the healthcare associated infection prevention. I find HAI Watch   site very informative in this aspect. 

HAI Watch is the  resource for collateral and supplies to help keep the  organization aware of the importance of healthcare associated infection prevention..... 

I really appreciate the efforts like the HAI Education Program a  part of a national infection awareness campaign for healthcare professionals called “Not on My Watch” and will provide the facility with a toolkit that contains informational flyers, patient safety tips and posters. I hope the info will definitely help the healthcare professionals in protecting the patients from preventable hospital infections....

New research finding may change direction of vaccine research for M. tuberculosis

New research finding may change direction of vaccine research for M. tuberculosis

FDA Acceptance of New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder..

Vilazodone(see structure) is an antidepressant which is currently under  development by Clinical Data for the treatment of major depressive disorder, and as of 2009 has completed two phase III clinical trials with positive results. An NDA was submitted on March 23rd, 2010 in the United States and is currently pending approval by the FDA which, if approved, will likely precede vilazodone's availability on the market by the end of 2010.

Now the company claims that FDA has accepted for filing the Company's New Drug Application (NDA) for vilazodone for the treatment of major depressive disorder (MDD).

Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT_1A receptor partial agonist. The NDA will be subject to a standard review. 

“The acceptance of the NDA for review by the FDA is another positive step toward our goal of bringing vilazodone to market, and if approved, vilazodone will offer a novel treatment to the millions of people suffering from depression”  says Carol R. Reed, M.D., Executive Vice President and Chief Medical Officer of Clinical Data.....

Ref : http://www.clda.com/uploads/CLDA%20NDA%20acceptance%20FINAL.pdf

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA

Lytix Biopharma receives approval to initiate Phase I/IIa clinical trial of Lytixar for MRSA