FDA approves Afinitor drug for tuberous sclerosis complex

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 the same drug has been approved for Tuberous sclerosis or tuberous sclerosis complex (TSC a rare, multi-system genetic disease that causes benign tumours to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin ) ….more

FDA approves cancer drug Afinitor for treatment of rare genetic disorder

 We know that Afinitor ( see structure) is an inhibitor of mTOR (mammalian target of rapamycin), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation and inhibition of mTOR kinase activity. Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.

Afinitor is specifically indicated for the treatment of advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. Afinitor is supplied as a 5 mg or 10 mg tablet designed for oral administration. The recommended initial dose of the drug is 10 mg, to be taken once daily at the same time every day, either with or without food. Afinitor tablets should be swallowed whole with a glass of water; they should not be chewed or crushed....Now FDA approves the drug....

 FDA approves cancer drug Afinitor for treatment of rare genetic disorder   

Fight against Ventilator-Associated Pneumonia....

In continuation of my update on "Pneumonia and its prevention..."

When I read an article from  Emedicine,  was surprised to see the analysis by the author. I quote the following lines...

 Hospital-acquired pneumonia (HAP) is pneumonia that develops 48 hours or longer after admission to a hospital.

• Ventilator-associated pneumonia (VAP) is pneumonia that develops 48 hours or longer after mechanical ventilation is given by means of an endotracheal tube or tracheostomy.
• Health care–associated pneumonia is pneumonia that occurs in persons in one of the following groups:
  • Patients who have been hospitalized in an acute care facility for 2 or more days within 90 days of the infection
  • Residents of a nursing home or long-term care facility
  • Patients who received intravenous antibiotic therapy, chemotherapy, or wound care within the last 30 days of the current infection
  • Patients who receive hemodialysis in any setting

HAP is the second most common nosocomial infection. HAP increases a patient's hospital stay by approximately 7-9 days and can increase hospital costs by an average of $40,000 per patient. and 

 Frequency

VAP is a complication in as many as 28% of patients who receive mechanical ventilation. The incidence of VAP increases with the duration of mechanical ventilation. Estimated rates are 3% per day for the first 5 days, 2% per day for days 6-10, and 1% per day after day 10.

Mortality/Morbidity

The crude mortality rate for VAP is 27-76%. Pseudomonas or Acinetobacter pneumonia is associated with increased mortality rates compared with other organisms. Studies have consistently shown that a delay in starting appropriate and adequately dosed antibiotic therapy increases the mortality risk...

We had "International Infection Prevention Week" a forth night ago,  but still we need to create awareness about such infections.   I think we need to give due importance for VAP too. Though,  there are many organizations, which are trying to create awareness and solutions for this problem, I find Kimberly Clark corporation's efforts really  interesting and  commendable. So let us join hands with the corporation to spread the awareness....

One can get more info with the link :

http://vap.kchealthcare.com

Telbivudine Given to Mothers with Hepatitis B Reduces Infection Rate in Infants

We knew that, Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo (Europe) and Tyzeka (United States). Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance.

Now researchers from American Association for the Study of Liver Diseases (AASLD), lead by Dr. Calvin Pan, have come up with some interesting finding, i.e., Telbivudine in the second to third trimesters of pregnancy lead to  no transmission of HBV to newborns was detected at 28 weeks postbirth.  The study concluded that both the mothers and new born. 

For this study, pregnant women with high level of HBVDNA enrolled in the treatment arm of the study were given 600 mg daily of Telbivudine. All newborns received three doses of hepatitis B vaccine. Patients in the treatment arm achieved sustained virologic response rate (SVR) of 53 percent prior to delivery and 62 percent four weeks after delivery. None of the patients in the control arm achieved SVR at either point. 

Only four percent of newborns in the treatment arm tested positive for hepatitis B, whereas 23 percent of newborns from the control group tested positive. None of the patients treated with Telbivudine had to stop treatment due to adverse events. No congenital deformities were observed up to 28 weeks after birth. There were no measurable differences in postpartum health issues for mothers and newborns between the treatment and control groups. 

Dr. Pan realizes the limitations of this study, “The infant follow up is limited to 28 weeks after birth. Even though it is good enough to define the failure rate of transmission prevention, the long term safety data for the infant is missing. Hypothetically, antiviral therapy and immunoprophylaxis can be effective in blocking transmission that occurs during late pregnancy or delivery, but the mechanism of intrauterine transmission remains a puzzle. Though more studies are needed in the field to provide a comprehensive strategy to prevent HBV vertical transmission, in my opinion its is significant achievement......

Ref : http://www.aasld.org/lm/press/Pages/PressReleaseTelbivudine.aspx   

FDA and EMA accept regulatory submissions of vandetanib for advanced medullary thyroid cancer

We know that, Vandetanib (proposed trade name Zactima), also known asZD6474, is an antagonist of the vascular endothelial growth factor receptor (VEGFR) and the epidermal growth factor receptor (EGFR). It is a tyrosine kinase inhibitor. Drug has a third target: inhibits RET-tyrosine kinase activity, an important growth driver in certain types of thyroid cancer and is being developed by AstraZeneca. It is a medication currently undergoin  clinical trials as a potential targeted treatment for non–small-celllung cancer.

Now US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have accepted regulatory submissions for review of the investigational drug vandetanib in the treatment of patients with advanced medullary thyroid cancer (MTC). The FDA also granted priority review status for the new drug application and set a Prescription Drug User Fee Act (PDUFA) action date of 7 January 2011. More...

Turmeric component (curcumin) enhances chemotherapy's suppression of head and neck cancer

In continuation of my update on Curcumin, I found this info interesting to share with.., i.e.,  researchers with UCLA's Jonsson Cancer Center have found, when combined with the drug Cisplatin, turmeric enhances the chemotherapy's suppression of head and neck cancer cell growth. Previous studies have shown it can suppress the growth of certain cancers. The study, done in cells in Petri dishes and then in mouse models is of great importance.

A 2005 study by Wang and Srivatsan first showed that curcumin suppressed the growth of head and neck cancer cells, first in cells and then in mouse models. In the animal studies, the curcumin was applied directly onto the tumors in paste form because it did not dissolve in saline, which would have allowed it to be injected. n need of a better way to deliver the curcumin, the team collaborated with Dr. Kapil Mehta of M.D. Anderson Cancer Center and found that encapsulating the curcumin in a liposome, an artificially prepared vehicle that enclosed the spice component within its membrane, made the treatment injectable. The curcumin was injected into the tail vein of a mouse, where it circulated into the blood stream, slowing down and eventually stopping the cancer growth, a study in 2008 found.

"This was a very positive finding, developing an efficient way to deliver the treatment," Wang said. "Our study also showed that the curcumin was very well tolerated."

In this study, the team wanted to combine the curcumin with the chemotherapeutic drug Cisplatin, which is very toxic at the doses needed to fight head and neck cancers, damaging kidneys, the ears and the bone marrow. They hoped that if they added curcumin to the mix, they might be able to lower the Cisplatin dose and cause less organ damage. Their finding, that the curcumin made the Cisplatin work better, was very promising.

More....

EPO grants new patent to Silence Therapeutics’ RNAi structural modification technology

In continuation of my update on RNAi...........

EPO grants new patent to Silence Therapeutics’ RNAi structural modification technology

Sanofi-Aventis’ Teriflunomide Comes Up Trumps in Two-Year Phase III MS Trial ....

Sanofi-aventis reported positive two-year data from a Phase III trial with its oral disease-modifying multiple sclerosis (MS) drug teriflunomide. Results from the international thousand-patient TEMSO study showed that both evaluated doses of teriflunomide reduced the annualized MS relapse rate by 31% in comparison with placebo. The 14 mg and 7 mg teriflunomide doses resulted in a reduction in the risk of disability progression by 30% and 24%, respectively, when compared with placebo.  

More..

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

In continuation of my update on carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

In continuation of my update on carfilzomib

Onyx Pharmaceuticals announces delay in NDA filing for carfilzomib

FDA approves fingolimod drug for multiple sclerosis...

Fingolimod (see structure), a drug modified from a fungus  (Isaria sinclairii), a structural analogue of sphingosine and gets phosphorylated by sphingosine kinases in the cell originally found in Asian wasps, prevents autoimmune attacks by trapping white blood cells in the body's lymph nodes. Two large Phase III clinical studies published in February found that fingolimod was at least twice as effective in preventing MS attacks when compared to placebo or current treatments. 

Research on additional uses for fingolimod continues at the University of Chicago, including a new clinical trial in patients with progressive MS, for which there are no available treatments. With fingolimod adding to the recent boom of new MS therapies, and with a number of clinical trials for new therapies in progress, patients should be sure to seek out an experienced MS center for their care.

As per the claim by the lead researcher, Anthony Reder, MD, Professor of Neurology at the University of Chicago Medical Center,  fingolimod is first oral medication for multiple sclerosis was approved  by the Food & Drug Administration. He also claims that'

"We have six drugs right now, and they all involve injections. So the convenience alone of a pill is a major change in how we treat MS."

Hope people suffering from MS, (A chronic, neurologic disorder, which affects roughly 400,000 Americans and 2.5 million people around the world.  MS can cause issues with walking and movement, fatigue, weakness, pain, and loss of vision. Patients with relapsing-remitting MS suffer from intermittent and unpredictable immune system attacks that can damage the brain, spinal cord, and eyes) breathe a sigh of relief..

More..

Rufinamide therapy is effective in reducing partial seizure frequency...

Rufinamide(see structure) is an anticonvulsant medication and a triazole derivative, was developed in 2004 by Novartis Pharma, AG, and is manufactured by Eisai. It is used in combination with other medication and  therapy to  treat  Lennox–Gastaut  syndrome and various other seizure disorders. Rufinamide.

Rufinamide was approved by the US FDA on November 14, 2008 as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. Its official FDA-approved labeling does not mention use in the treatment of partial seizures inasmuch as clinical trials submitted to the FDA were marginal.

Interestingly, now researchers from the Arkansas Epilepsy Program found treatment with rufinamide results in a significant reduction in seizure frequency compared with placebo, for patients with uncontrolled partial-onset seizures (POS).

Researchers found that treatment with rufinamide resulted in a statistically significant reduction in total partial seizure frequency compared with placebo. Results also showed a 50% reduction in responder rate and total partial seizure frequency rate in patients treated with rufinamide. Several exploratory efficacy variables, including at least 75% responder rate and increase in the number of seizure-free days, were also associated with notably better results for rufinamide.

With respect to efficacy by seizure type, rufinamide was significantly superior to placebo for complex partial seizures, the most common seizure type, and numerically superior to placebo for simple partial seizures and secondarily generalized partial seizures. The median reduction in secondarily generalized partial seizures of 40% in this study is consistent with that previously observed at identical rufinamide dosage. As per the claim by the lead researcher Dr. Victor Biton,

"Overall, there were no significant pharmacokinetic (PK) effects on either rufinamide or any second-generation AED when given with other medications."

The research team confirmed PK results found in previous studies-showing lower oral bioavailability of rufinamide at higher doses, increased clearance of rufinamide with increasing body weight, and no effect of prolonged rufinamide dosing on the PK of rufinamide.

More....

Ingredient (Triclosan) in soap points toward new drugs for Toxoplasmosis !

We know that, Triclosan (see structure)  is an antibacterial ingredient in some soaps, toothpastes, odor-fighting socks, and even computer keyboards. Now researchers lead by Dr. Rima McLeod from The University of Chicago, have come up with interesting findings about this drug, i.e., triclosan's molecular structure can be used as  the model for developing other potential medications for toxoplasmosis. 

In the study, Rima McLeod and colleagues point out that toxoplasmosis is one of the world's most common parasitic infections (spread by the parasite Toxoplasma gondii,  T. gondii), from contact with feces from infected cats, eating raw or undercooked meat, and in other ways. Many have no symptoms because their immune systems keep the infection under control and the parasite remains inactive. But it can cause eye damage and other problems, even becoming life threatening in individuals with immune systems weakened by certain medications and diseases like HIV infection, which allow the parasite to become active again, and in some persons without immune compromise. Most current treatments have some potentially harmful side effects and none of them attack the parasite in its inactive stage.

The scientists knew from past research that triclosan has a powerful effect in blocking the action of a key enzyme that T. gondii uses to live. As per the claim by the researchers, Triclosan, however, cannot be used as a medication because it does not dissolve in the blood, how ever  one can use triclosan's molecular structure as the model for developing other potential medications, including some that show promise as more effective treatments for the disease.  Hope this research will lead to a better drug than Triclosan without any carcinogenecity and many other side effects associated with this drug..

Ref : http://pubs.acs.org/stoken/presspac/presspac/abs/10.1021/jm9017724

Phase 3 clinical study demonstrates efficacy of metformin therapy in type 2 diabetes

Phase 3 clinical study demonstrates efficacy of metformin therapy in type 2 diabetes

Enzyme telomerase activating compound discovered....

In continuation of telomerase and its importance...

Sierra Sciences, in collaboration with TA Sciences, Geron Corporation, PhysioAge, and the Spanish National Cancer Research Center (CNIO), has announced the first compound ever discovered that activates the enzyme telomerase in the human body - a critical prerequisite for technology that could arrest or reverse the aging process in humans. This compound is a natural product derived nutraceutical known as TA-65.

TA-65, exclusively licensed to TA Sciences from Geron Corporation, is a >95% pure single chemical entity isolated from a proprietary extract of the dried root of Astragalus membranaceus and formulated into 5- to 10-mg capsules with inert excipients. Starting doses of 5–10 mg/day were considered safe on the basis of historical usage of extracts. Some subjects increased their dosage after several months on the product to 25–50 mg/day. Cumulative dose consumed during the year was recorded for each subject and used for preliminary dose–response analysis.

Researchers discovered that TA-65 was associated with a statistically significant "age-reversal" effect in the immune system, in that it led to declines in the percentage of senescent cytotoxic T cells and natural killer cells after six to twelve months of use. In addition, further analysis with automated high-throughput confocal microscopy (HT-qFISH) revealed a decline in the percentage of white blood cells with critically short telomeres after twelve to eighteen months of use.

Telomere shortening is thought to be the "clock of aging" contained within the human body. It has been repeatedly demonstrated that a human cell that does not undergo telomere shortening will divide indefinitely and is, by all available measurements, immortal.

Researchers reports that TA-65 can cause telomerase, an enzyme that lengthens telomeres, to become active in human cells.  Telomerase activation by TA-65 was shown to lengthen the shortest telomeres in humans, potentially extending human lifespan and healthspan. Telomerase activation is thought to be a keystone of future regenerative medicine and a necessary condition for clinical immortality. Although TA-65 is probably too weak to completely arrest the aging process, it is the first telomerase activator recognized as safe for human use.

"We are on the cusp of curing aging," said William Andrews, Ph.D., co-author of this study and President and CEO of Sierra Sciences, LLC. "TA-65 is going to go down in history as the first supplement you can take that doesn't merely extend your life a few years by improving your health, but actually affects the underlying mechanisms of aging. Better telomerase inducers will be developed in the coming years, but TA-65 is the first of a whole new family of telomerase-activating therapies that could eventually keep us young and healthy forever."

Telomerase activation has potential medical applications beyond extending human lifespan.  Epidemiological studies have shown that short telomeres in humans are a risk factor for diseases including, among others, atherosclerosis, diabetes, Alzheimer's, and cancer. The present study also reports encouraging news on the effect of TA-65 on the body's immune system. Infectious diseases lead to telomere shortening in the immune system, as immune cells divide to fight infections. Telomerase activation should prevent this telomere shortening and allow the body's immune system to fight a chronic infection indefinitely.

The present study on TA-65 lends support to this hypothesis. In individuals infected with CMV, a virus which prematurely ages the immune system and significantly reduces life expectancy, TA-65 caused an apparent "age reversal" of approximately 5 to 20 years based on one biomarker of immune aging. For the same reason, telomerase activation is a potential treatment for AIDS.

"We tend to see HIV turning into AIDS when the cells of the immune system develop critically short telomeres," said Andrews...

HIV can essentially cause the immune system to die of old age while the majority of the body is still young and therefore the researchers are hopeful that a telomerase activator could theoretically prevent an HIV-positive individual from ever developing AIDS....

Ref : http://www.liebertonline.com/doi/abs/10.1089/rej.2010.1085