Friday, May 29, 2015

Chemical found in stinging nettles and ants could improve cancer drug

The contrasting mechanisms of action of two classes of organometallic anticancer catalysts.

A cancer drug could be made 50 times more effective by a chemical found in stinging nettles and ants, new research finds. Researchers at the University of Warwick found that when the chemical, Sodium Formate, is used in combination with a metal-based cancer treatment it can greatly increase its ability to shut down cancer cells.

Developed by Warwick's Department of Chemistry, the drug, a compound of the metal ruthenium called JS07, is capable of exploiting a cancer cell's natural weaknesses and disrupts its energy generation mechanism.

Laboratory tests on ovarian cancer cells have shown that when used in combination with Sodium Formate JS07 is 50 times more effective than when acting alone. Derived from formic acid which is commonly found in a number of natural organisms including nettles and ants, Sodium Formate (E-237) is more commonly used as a food preservative.

The Warwick researchers developed a novel method for binding Sodium Formate with JS07 to form a more potent form of the drug. The researchers subsequently found that the potent form of JS07 acts as a catalyst when it interacts with a cancer cell's energy-generating mechanism. This interaction disrupts the mechanism, causing the cell's vital processes to cease functioning and for the cell to shut down.

Thursday, May 28, 2015

Olive ingredients may prevent Alzheimer's disease

It has long been proven that people who follow a Mediterranean diet and keep physically and mentally active are less likely to suffer from dementia. Olives in particular appear to play a key role in this regard. But just what are the substances contained in these small, oval fruit that are so valuable? This is what a Hessen-based group of researchers from the Goethe University Frankfurt, the Technical University (TU) of Darmstadt and Darmstadt company N-Zyme BioTec GmbH intends to find out. The three-year project "NeurOliv" has a project volume of 1.3 million Euros and is funded by the Federal Ministry of Education and Research as part of the high-tech initiative "KMU-innovativ Biochance".

This collaboration combines a number of approaches, the initiative of which came from N-Zyme BioTec GmbH. The aim is to use substances contained in olives to develop new functional food for the ageing society, which will protect against Alzheimer's disease. "We want to test whether olive polyphenols can even help to cure the disease. This is why we believe our products also relate to the pharmaceutical sector", says Dr. Joachim Tretzel, Managing Director of N-Zyme BioTec GmbH. The high-tech initiative of the German government was set up to fund small and medium-sized enterprises.

Olive oil :

Wednesday, May 27, 2015

New anti-clotting therapy no better than established anticoagulants

A novel therapy that would allow doctors to turn the body's blood-clotting ability off and on in a more controlled way was about as effective as established anticoagulants in patients undergoing angioplasty but was associated with higher rates of moderate to severe bleeding, according to an analysis of data from a terminated Phase III trial presented at the American College of Cardiology's 64th Annual Scientific Session. The study was officially halted in August due to an excess of severe allergic reactions, so authors caution that the data should be considered exploratory given the early termination.

Before the trial was stopped, 3,232 patients undergoing angioplasty, a procedure to open blocked coronary arteries, were enrolled in the study at 225 hospitals in 17 countries including North America and Europe. The study was designed to compare the safety and efficacy of the REG1 Anticoagulation System and bivalirudin--a commonly used anticoagulant--in a total of 13,200 patients. Patients were equally randomized to the bivalirudin or REG1 in an open-label fashion and data was collected at three and 30 days.
No differences were found between patients receiving REG1 compared to bivalirudin in terms of the study's primary efficacy endpoint--a composite of all-cause death, heart attack, stroke or urgent revascularization, which was reported in 6.7 percent of patients in the REG1 arm and 6.4 percent of patients receiving bivalirudin three days after angioplasty. Efficacy was still comparable at 30 days.

The REG1 system failed to show a benefit in the primary safety endpoint of bleeding compared to bivalirudin. Using a validated bleeding scale, patients receiving REG1 had a 0.4 percent rate of severe or fatal bleeding compared to 0.1 percent with patients who were given bivalirudin for anticoagulation. Moderate to severe bleeding was significantly higher in the REG1 group compared with bivalirudin.

Tuesday, May 26, 2015

Viagra can have anti-cancer, anti-Alzheimer's disease effects if used with new drugs

Chaperone proteins play an important role in protein folding in human cells and in bacteria and are promising new targets for drugs to treat cancer and Alzheimer's disease and for novel antiviral drugs and antibiotics. How existing drugs such as Viagra or Cialis and a derivative of the drug Celebrex, for example, can reduce the activity of a specific chaperone protein, with the potential for anti-tumor and anti-Alzheimer's disease effects, is described in a Review article in DNA and Cell Biology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the DNA and Cell Biology website until April 9, 2015.

In the article "HSPA5/Dna K May Be a Useful Target for Human Disease Therapies", Laurence Booth, Jane Roberts, and Paul Dent, Virginia Commonwealth University, Richmond, provide a comprehensive discussion of the HSPA5/Dna K chaperone protein and the published evidence for its role in various human diseases. The authors describe how OSU-03012, an experimental compound derived from the drug celecoxib (Celebrex) interacts with Viagra or Cialis to reduce levels of chaperone proteins. Reduced levels of HSPA5 and Dna K can interfere with virus replication, promote bacterial cell death, and even make drug-resistant "superbugs" susceptible to existing antibiotics.

"Drugs like Celebrex and Viagra are readily available and generally recognized as safe. This study by Booth and colleagues may lead to new applications of these relatively new medicines," says Carol Shoshkes Reiss, PhD, Editor-in-Chief, of DNA and Cell Biology and Professor, Departments of Biology and Neural Science, New York University, NY. "The potential impact, if the experiments described are translatable to human disease, could be paradigm-shifting. The potential applications are serious antibiotic resistant infections, chemotherapy-resistant cancers, and neurodegenerative disease ranging from Parkinson's disease to Huntington's or Alzheimer's disease."

Monday, May 25, 2015

Promising new natural treatment for Alzheimer's disease nears clinical trial

Figure imgf000060_0001

 Withania Somnifera (Ashwagandha) Withanolides Max. 1.5%

A promising new natural treatment for Alzheimer's disease is moving toward clinical trials. This will be a major step forward as there is nothing on the market that slows the progression of Alzheimer's.

Muraleedharan Nair, Michigan State University natural products chemist, has patented a botanical compound, withanamides. His spinoff company, Natural Therapeutics, will begin the trials as soon as funding is in place.

To date, none of the major pharmaceutical companies - Merck, Eli Lilly, Bristol-Myers Squibb - have been able to produce an effective treatment that passed human clinical trials, Nair said.

"This particular research has focused on Ashwagandha, an herbal remedy that's been used in Eastern medicines for centuries," he said. "Our compound withanamides may work to prevent Alzheimer's disease at the onset, and it also could prevent its progression."

While plants cannot be patented, compounds from it can. MSU holds the patent for withanamides, and earlier research revealed that the compound, found in the plants' seeds, proved to be a powerful anti-oxidant - double the strength of what's on today's market. The potent compound has shown that it can protect cells against damaging attacks by a rogue protein ¬- the earliest stage of Alzheimer's.

Alzheimer's begins when a specific protein starts breaking, or cleaving, at the wrong place to produce an unwanted fragment. This bad fragment, called BAP, stresses cells' membranes, sparks plaque formation and eventually kills the cells. This attack begins in the frontal lobe, erasing memories and continuing its unrelenting assault deeper into the brain.

A complicating factor is that the majority of protein cleaving is a natural, healthy process. Pharmaceutical companies, however, have focused their efforts on blocking the tiny faction of bad cleaving of the protein producing BAP.

Friday, May 22, 2015

Naproxen and omeprazole combination effective in preventing bladder cancer

The anti-inflammatory class of drugs NSAIDs have shown great promise in preventing cancers including colon, esophagus and skin. However, they can increase the risks of heart attacks, ulcers and rare but potentially life-threatening bleeds.

A new study suggests there may be ways to reduce these dangerous side effects. Collaborators from the University of Michigan, the National Cancer Institute and the University of Alabama looked at naproxen, which is known to have a lower cardiovascular risk than other NSAIDs. Naproxen, like most NSAIDs and aspirin, does increase the risk for gastric ulcers or bleeding. Here, the researchers used the proton pump inhibitor omeprazole, a commonly used acid inhibitor, in combination with naproxen and tested its effects on cancer prevention in a rat model of bladder cancer.

They found that naproxen reduced the incidence of bladder cancer by 75 percent in rats. Omeprazole by itself did not affect the development of cancer but it also did not interfere with the effect of naproxen at preventing tumors. The rats who received naproxen alone or naproxen with omeprazole developed cancer at similarly low rates, while all rats receiving omeprazole alone or no treatment developed bladder cancer.

Clinical data in humans has previously shown combining omeprazole plus naproxen reduced gastric toxicity roughly 70 percent.

The authors also found that intermittent dosing with naproxen (three weeks on the drugs, followed by three weeks off) was highly effective and likely to reduce gastric toxicity. However, it does not have the clear clinical data supporting reduced gastric toxicity associated with naproxen and omeprazole.

"Our study shows that naproxen works just as well with a proton pump inhibitor as without. This provides proof of principle that this could be a valuable cancer prevention strategy and one hopes it can advance quickly to a clinical trial for those at high risk of colon, esophageal, squamous cell skin cancer or potentially other cancers," says lead study author Ronald A. Lubet, Ph.D., a scientist with the Chemopreventive Agent Development Research Group at the National Cancer Institute.

Thursday, May 21, 2015

New drug shows promise in driving insulin-producing beta cells to multiply

In a screen of more than 100,000 potential drugs, only one, harmine, drove human insulin-producing beta cells to multiply, according to a study led by researchers at the Icahn School of Medicine at Mount Sinai, funded by JDRF and the National Institutes of Health, and published online today in Nature Medicine.

Diabetes results from too few insulin-producing "beta cells" in the pancreas secreting too little insulin, the hormone required to keep blood sugar levels in the normal range. The disease affects 380 million people worldwide, and leads to major medical complications: heart attack, stroke, kidney failure, blindness and limb amputation.

The Mount Sinai study found that harmine drove the sustained division and multiplication of adult human beta cells in culture, a feat that had eluded the field for years. In addition, harmine treatment tripled the number of beta cells and led to better control of blood sugar in three groups of mice engineered to mimic human diabetes.

"Our results provide a large body of evidence demonstrating that the harmine drug class can make human beta cells proliferate at levels that may be relevant for diabetes treatment," said senior study author Andrew Stewart, MD, Director of the Diabetes, Obesity and Metabolism Institute at the Icahn School of Medicine. "While we still have a lot of work to do in improving the specificity and potency of the harmine and related compounds, we believe these results represent a key step toward more effective future treatment of diabetes."

Loss of insulin-producing beta cells has long been recognized as a cause of Type 1 diabetes, in which the immune system mistakenly attacks and destroys beta cells. In recent years, researchers have concluded that a deficiency of functioning beta cells also contributes importantly to Type 2 diabetes. Thus, developing drugs that can increase the numbers of healthy beta cells is a major priority in diabetes research.

Ref :

Wednesday, May 20, 2015

New injectable polymer could strengthen blood clots

A 3D rendering of fibrin forming a blood clot, with PolySTAT (in blue) binding strands together

In the initial study with rats, 100 per cent of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. Only 20 per cent of rats treated with a natural protein that helps blood clot survived.

“Most of the patients who die from bleeding die quickly,” said co-author Dr. Nathan White, an assistant professor of emergency medicine who teamed with UW bioengineers and chemical engineers to develop the macromolecule. “This is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”
According to a statement, the UW team was inspired by factor XIII, a natural protein found in the body that helps strengthen blood clots.
Normally after an injury, platelets in the blood begin to congregate at the wound and form an initial barrier. Then a network of specialised fibres called fibrin start weaving themselves throughout the clot to reinforce it.

Tuesday, May 19, 2015

New cancer drug enters phase I clinical trials in humans

"Even though they have elevated levels of procaspase-3, cancer cells never turn the enzyme on. So they keep growing and become tumors," he said. "PAC-1 restores the activity of procaspase-3 and, because the enzyme is elevated in cancer cells, it targets cancer cells over non-cancerous cells."  PAC-1.svg

A new drug that prompts cancer cells to self-destruct while sparing healthy cells is now entering phase I clinical trials in humans. The drug, called PAC-1, first showed promise in the treatment of pet dogs with spontaneously occurring cancers, and is still in clinical trials in dogs with osteosarcoma.

The compound was discovered and is being developed based on the hypothesis that most cancers have elevated levels of an enzyme called procaspase-3," said University of Illinois chemistry professor Paul Hergenrother, who discovered the anti-cancer effects of PAC-1 more than a decade ago. "Procaspase-3 is an enzyme that, when turned on, kills cells."

Cancer cells, however, override this normal cell-recycling pathway, he said.

Early tests of the drug's effectiveness came when Hergenrother collaborated with U. of I. veterinary clinical sciences professor Timothy Fan, who tested PAC-1 in his canine cancer patients. These clinical trials helped the researchers find the best way to deliver the drug - it is now in pill form for both human and canine patients - and led to new insights into the drug's activity and potential, Fan said.

Monday, May 18, 2015

EMA extends approval of Vectibix plus FOLFIRI as first-line treatment for wild-type RAS mCRC

Amgen (NASDAQ: AMGN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion to extend the marketing authorization for Vectibix® (panitumumab) to include combination with FOLFIRI- FOLFIRI is a chemotherapy regimen for treatment of colorectal cancer. It is made up of the following drugs:
  • FOL – folinic acid (leucovorin), a vitamin B derivative used as a "rescue" drug for high doses of the drug methotrexate, but increases the cytotoxicity of 5-fluorouracil;
  • F – fluorouracil (5-FU), a pyrimidine analog and antimetabolite which incorporates into the DNA molecule and stops synthesis; and
  • IRI – irinotecan (Camptosar), a topoisomerase inhibitor, which prevents DNA from uncoiling and duplicating.
 (an irinotecan-based chemotherapy) as first-line treatment in adult patients with wild-type RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have wild-type RAS tumors.

"Adding Vectibix to chemotherapy as first-line treatment in patients with wild-type RASmetastatic colorectal cancer has been shown to result in better responses than chemotherapy alone," said Elliott M. Levy, M.D., senior vice president of Global Development at Amgen. "The CHMP recommendation is an important step toward increasing the treatment options for patients with this aggressive disease and helping improve outcomes in the European Union."

Friday, May 15, 2015

EMA's CHMP backs JINARC (tolvaptan) for autosomal dominant polycystic kidney disease


Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated with congestive heart failurecirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolsama & Tolvat and by Lupin under the brand name Resodim.
Otsuka Pharmaceutical Co., Ltd. announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended JINARC® (tolvaptan) for approval. This treatment has been recommended to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with chronic kidney disease (CKD) stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease.

Tolvaptan was developed over a period of 26 years through the persevering efforts of researchers in Otsuka’s Japanese pharmaceutical research centre. Upon discovering a cell signaling pathway that causes renal cysts to proliferate and enlarge, Otsuka launched an effort in 2004 to develop a drug for the disease in conjunction with the world’s leading ADPKD medical specialists.

Thursday, May 14, 2015

Study shows efficacy of YONDELIS (trabectedin) in patients with soft-tissue sarcoma


In continuation of my update on trabectedin

PharmaMar announced that the European Journal of Cancer published online data from a large retrospective study with soft-tissue sarcoma (STS) patients carried out at 25 French centers confirming that in routine practice YONDELIS® (trabectedin) shows comparable or better clinical outcomes than those observed in clinical trials . The results add to previous evidence from other studies with trabectedin , including the compassionate expanded access program of 1895 patients with incurable disease , demonstrating that response and disease control rates are higher than expected. The authors describe that long-term treatment of multiple types of STS patients without progressive disease delayed progression and improved survival compared to those who stopped it after six cycles, as recently suggested in the T-DIS studyiii. In this routine real-life scenario, the median progression-free survival (PFS) and overall survival (OS) were 4.4 and 12.2 months, respectively after a median follow-up of 22 month. Of the 304 patients who achieved non-progressive disease after six cycles, 227 continued receiving trabectedin and obtained significant superior PFS (11.7 versus 7.6 months) and OS (24.9 versus 16.9 months) than those who did not. The recent study reinforces an approach of early administration of YONDELIS® (trabectedin) to optimize its efficacy as second-line treatment in patients that will probably benefit from this drug. Despite the limitations of the study, the investigators emphasize that this clinical strategy may achieve longer disease control without compromising the safety profile of the treatment, given that a third of the patients received more 6 or more cycles of the drug and were able to tolerate longer treatments.

Study shows efficacy of YONDELIS (trabectedin) in patients with soft-tissue sarcoma

Wednesday, May 13, 2015

Bionomics to present data from DisrupTOR-1 trial at ASCO Genitourinary Cancers Symposium


Bionomics Limited (ASX:BNO, ADR:BMICY) is to present important additional data from the DisrupTOR-1 trial of BNC105 in patients with metastatic renal cancer at the ASCO Genitourinary Cancers Symposium in Orlando, Florida. The data will be presented by Dr. Sumanta Pal of the City of Hope Comprehensive Cancer Center in California in his poster presentation.

The new data identifies Ferritin and IL-8 as two baseline biomarkers that correlate with an improved progression free survival (PFS) in patients. Elevated baseline Ferritin and lower baseline IL-8 were associated with improved PFS (P=0.0291 and P=0.0149, respectively). Eighty nine percent of patients expressing elevated plasma levels of Ferritin and lower plasma levels of IL8 at baseline were disease progression free (PFS) at 6 months.

"The DisrupTOR-1 trial offered a unique opportunity to assess biomarkers related to the activity of BNC105. Interestingly our findings suggest that baseline levels of Ferritin and IL-8 may predict an excellent clinical outcome with the combination of Afinitor with BNC105. Plans are underway already to validate this finding in a biomarker-driven trial," said Dr. Pal, Co-Director of the Kidney Cancer Program at the Department of Medical Oncology & Experimental Therapeutics of the City of Hope Comprehensive Cancer Center.

"This is a compelling improvement compared to the 34% PFS observed at six months in the unselected population," said Dr. Deborah Rathjen, Bionomics' CEO and Managing Director.
"These results indicate that moving forward, biomarker-based patient selection has the potential to provide guidance and optimise clinical outcomes in the treatment of renal cancer, presenting a range of new possibilities for BNC105. We will continue to explore further data and the options for the advancement of the compound.

"Bionomics to present data from DisrupTOR-1 trial at ASCO Genitourinary Cancers Symposium

Tuesday, May 12, 2015

Sorafenib, sunitinib provide no benefit to patients with locally advanced kidney cancer

Findings from a federally funded study suggest that patients with locally advanced kidney cancer should not be treated with either adjuvant (post-surgery) sorafenib or sunitinib. The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery (5.6 years) and those treated with placebo (5.7 years). The study will be presented at the upcoming 2015 Genitourinary Cancers Symposium in Orlando.

"These drugs didn't reduce disease recurrence, but on average they did not appear to worsen patient outcomes either," said lead study author Naomi B. Haas, MD, an Associate Professor of Medicine at the Abramson Cancer Center of the University of Pennsylvania in Philadelphia, Pa. "We are still analyzing the various groups of patients enrolled on this trial, and we hope that analysis of patient specimens collected on this study may provide clues into subsets of patients who might still benefit from these therapies."

Treatment reduces risk of recurrence of C. difficile infection

In continuation of my update on metronidazole  &  vancomycin

Among patients with Clostridium difficile infection (CDI) who recovered following standard treatment with the antibiotics metronidazole or vancomycin, oral administration of spores of a strain of C difficilethat does not produce toxins colonized the gastrointestinal tract and significantly reduced CDI recurrence, according to a study in the May 5 issue of JAMA.

C difficile is the cause of one of the most common and deadly health care-associated infections, linked to 29,000 U.S. deaths each year. Rates of CDI remain at unprecedented high levels in U.S. hospitals. Clinical infection also has a recurrence rate of 25 percent to 30 percent among affected patients. Not all strains of C difficile produce toxins. Nontoxigenic C difficile strains that lack the genes for toxin production are also found in the hospital environment and can colonize hospitalized patients, although patients are usually asymptomatic. Gastrointestinal colonization by these nontoxigenic C difficilestrains (in both humans and hamsters) has shown promising results as a potential way to prevent CDI, according to background information in the article.

Dale N. Gerding, M.D., of the Edward Hines Jr. VA Hospital, Hines, Il., and Loyola University Chicago, Maywood, Il., and colleagues randomly assigned 173 adult patients who were diagnosed as having CDI (first episode or first recurrence) to receive 1 of 4 treatments: oral liquid formulation of nontoxigenic C difficile strain M3 (VP20621; NTCD-M3), 104 spores/d for 7 days (n = 43), 107 spores/d for 7 days (n = 44), 107 spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). Prior to enrollment, these patients had all successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe.

Monday, May 11, 2015

Taiho Oncology announces acceptance of TAS-102 NDA for review by FDA

Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical Co., Ltd. (Japan), today announced the New Drug Application (NDA) for TAS-102 (nonproprietary names: trifluridine and tipiracil hydrochloride), has been accepted for review by the U.S. Food and Drug Administration (FDA). TAS-102 is an oral combination investigational anticancer drug for the treatment of refractory metastatic colorectal cancer (mCRC).

TAS-102 is an investigational drug candidate for metastatic colorectal cancer. It is a combination of two active pharmaceutical ingredientstrifluridine, (see left structure) Trifluridine structure.svg Tipiracil.svg
a nucleoside analog (see right structure), and tipiracil hydrochloride, a thymidine phosphorylase inhibitor. Tipiracil hydrochloride prevents rapid metabolism of trifluiridine, increasing the bioavailability of trifluiridine.

"The FDA's filing of the TAS-102 NDA represents a significant milestone for our company and underscores the need for new treatment options for patients with refractory metastatic colorectal cancer," said Eric Benn, Taiho Oncology's president and chief executive officer. "Today, we are one step closer to our ultimate goal of gaining regulatory approval for TAS-102 and making it available to patients in the USA with this serious medical condition. We look forward to working closely with the FDA during the NDA review."

Friday, May 8, 2015

Anticoagulant fondaparinux lowers risk of major bleeding events, death in heart attack patients


Patients who experienced a certain type of heart attack who received the anticoagulant fondaparinux had a lower risk of major bleeding events and death both in the hospital and after six months compared to patients who received low-molecular-weight heparin (LMWH), although both groups had similar rates of subsequent heart attack or stroke, according to a study in the February 17 issue of JAMA.

Reducing bleeding events in patients receiving antithrombotic therapy is important since bleeding events are associated with increased mortality. Fondaparinux was associated with reduced major bleeding events and improved survival compared with LMWH (a class of anticoagulant medications) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI; a certain pattern on an electrocardiogram following a heart attack). Large-scale experience of the use of fondaparinux vs LMWH outside of a clinical trial setting has been lacking, according to background information in the article.

Karolina Szummer, M.D., Ph.D., of the Karolinska Institutet, Stockholm, Sweden, and colleagues analyzed data from a Swedish registry that included 40,616 patients with NSTEMI who received in-hospital treatment with fondaparinux or LMWH between September 2006 through June 2010, with follow-up through December 2010.

Thursday, May 7, 2015

New compound appears to play role in development of opioid tolerance

While opioids are a widely used treatment for pain, patients who take them on a regular basis can become tolerant, requiring a higher dose for continued pain relief. In a study published in Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®), researchers identified a compound that appears to play a role in the development of opioid tolerance. It may be possible to lessen the development of opioid tolerance if that compound is neutralized or blocked in patients taking opioids chronically for severe pain.

"Opioid tolerance is a growing problem among chronic pain patients and cancer patients in particular," said Chih-Peng Lin, M.D., assistant professor, Department of Anesthesiology, National Taiwan University College of Medicine. "We found that CXCL1, a protein produced by spinal cord tissue, contributes to opioid tolerance. By neutralizing CXCL1 in patients, we might help solve the problem of opioid tolerance."

Wednesday, May 6, 2015

Alcon Receives FDA Approval of Pazeo (olopatadine HCl) Ophthalmic Solution for Allergic Conjunctivitis


Olopatadine hydrochloride is an antihistamine (as well as anticholinergic and mast cell stabilizer), sold as a prescription eye drop (0.2% solution, Pataday (or Patanol S in some countries), manufactured by Alcon). It is used to treat itching associated with allergic conjunctivitis (eye  allergies). Olopatadine hydrochloride 0.1% is sold as Patanol (or Opatanol in some countries). A decongestant nasal spray formulation is sold as Patanase, which was approved by the FDA on April 15, 2008.  It is also available as an oral tablet in Japan under the tradename Allelock, manufactured by Kyowa Hakko Kogyo.

Alcon, the global leader in eye care and a division of Novartis, has received approval from the U.S. Food and Drug Administration (FDA) of Pazeo (olopatadine hydrochloride ophthalmic solution) 0.7%, for the treatment of ocular itching associated with allergic conjunctivitis. Pazeo solution is dosed one drop daily, and was approved with efficacy data at 24 hours, post dose.

Alcon Receives FDA Approval of Pazeo (olopatadine HCl) Ophthalmic Solution for Allergic Conjunctivitis

Eliglustat drug improves liver, spleen size and hemoglobin level in adults with Gaucher disease type 1

In continuation of my update on eliglustat  


Among previously untreated adults with Gaucher disease type 1, a genetic disease in which there is improper metabolism due to a defect in an enzyme, treatment with the drug eliglustat resulted in significant improvements in liver and spleen size hemoglobin level, and platelet count, according to a study in the February 17 issue of JAMA.

Gaucher disease type 1 is characterized by enlargement of the spleen and liver, anemia, low blood platelets, chronic bone pain, and the failure to grow properly. Untreated Gaucher disease type 1 is a chronic and progressive disorder associated with disability, reduced life expectancy, and, in some patients, life-threatening complications. The current standard of care is enzyme replacement therapy, which requires lifelong intravenous infusions every other week. A safe, effective oral therapy is needed, according to background information in the article. 

Pramod K. Mistry, M.D., Ph.D., F.R.C.P., of the Yale University School of Medicine, New Haven, Conn., and colleagues randomly assigned 40 untreated adults with Gaucher disease type 1 to receive eliglustat (twice daily; n = 20) or placebo (n = 20) for 9 months. Eliglustat is a novel oral medication, which showed favorable results for patients with this disease in a phase 2 trial. This phase 3 trial was conducted at 18 sites in 12 countries.

The researchers found that administration of eliglustat resulted in a reduction in spleen volume of approximately 30 percent compared with placebo, as well as improvements in hemoglobin level, decreased liver volume (-6.6 percent), and increased platelet count (41 percent). No serious adverse events occurred. No patient discontinued treatment over the course of the 9-month study because of a treatment-emergent adverse event.

Tuesday, May 5, 2015

New molecule shows promise in controlling HIV without using daily antiretroviral drugs

Scientists have created a new molecule that shows promise for controlling HIV without daily antiretroviral drugs. The molecule foils a wider range of HIV strains in the laboratory than any known broadly neutralizing HIV antibody and is more powerful than some of the most potent of these antibodies. In addition, the molecule safely protected monkeys from infection with an HIV-like virus during a 40-week study period. Together, the data suggest that the molecule could, with further research, be used to subdue HIV in humans. The authors note that the molecule potentially could be used as both a preventative drug and as a treatment. The new findings appear in the February 18 issue of the journal Nature.

"This innovative research holds promise for moving us toward two important goals: achieving long-term protection from HIV infection, and putting HIV into sustained remission in chronically infected people," said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

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Monday, May 4, 2015

Eli Lilly accepts committee recommendation to extend evacetrapib Phase 3 trial

We know that, Evacetrapib  is a  drug under  development by  Eli Lilly  and  company (investigational   name   LY2484595)      that inhibits cholesterylester transfer protein (CETP), which  transfers and thereby increases high-density lipoprotein and     lowers   low-density lipoprotein. It is thought that modifying lipoprotein levels modifies the    risk     of     cardiovascular   disease.   The  first  CETP inhibitor, torcetrapib, was unsuccessful because it increased levels of the hormone aldosterone and increased blood pressure, which led to excess cardiac events when it was studied.  Evacetrapib does not have the same effect. When studied in a small clinical trial in people with elevated LDL and low HDL, significant improvements were noted in their lipid profile.

A recent report states that,  Eli Lilly and Company (NYSE: LLY) has accepted the recommendation of the ACCELERATE study academic executive committee, based on emerging science in the cardiovascular field, to extend the Phase 3 trial of the investigational medicine evacetrapib by approximately six months. The decision is not based on any data from ACCELERATE, as both the academic committee and the company remain blinded to efficacy results............

Friday, May 1, 2015

Palbociclib extends progression-free survival in advanced breast cancer patients

In continuation of my update on Palbociclib

Palbociclib, an investigational oral medication that works by blocking molecules responsible for cancer cell growth, is well tolerated and extends progression-free survival (PFS) in newly diagnosed, advanced breast cancer patients, including those whose disease has stopped responding to traditional endocrine treatments. Results of the phase II study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania , were published this month in Clinical Cancer Research. Earlier phase I results by researchers at Penn Medicine contributed to the development of palbociclib, which was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic breast cancer patients just beginning to undergo endocrine therapy.

"The FDA approval has expanded treatments options for many metastatic breast cancer patients, but these new results are showing how effective the drug can also be for breast cancer patients who have already tried endocrine therapies and may be running out of options," said lead investigator Angela DeMichele, MD, MSCE , associate professor in the division of Hematology/Oncology and Epidemiology and co-leader of the Breast Cancer Research Program at the Abramson Cancer Center. "Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy."
The newly-published phase II trial primarily sought to evaluate disease response and control, while monitoring for the presence of side effects such as neutropenia, an abnormally low white blood cell count. Patients enrolled in the trial had previously undergone several prior chemotherapy and hormonal regimens for metastatic disease. Palboclib was administered once daily for 21 days each month.

Overall, researchers noted a median PFS, the time before a tumor worsens or the patient dies, of 3.7 months for patients taking the drug. However, patients with hormone receptor-positive (HR+) breast cancer -where the breast cancer cells depend on the hormones estrogen and progesterone to grow - had significantly longer PFS (5.1 months) compared to that of the HR-negative group (84 percent and 11 percent of the enrolled population, respectively). And those who had previously progressed through at least two rounds of hormonal therapy saw significantly greater benefits, suggesting substantial activity in the setting of acquired endocrine resistance.