Benefits of calcium and vitamin D in preventing fractures confirmed

Benefits of calcium and vitamin D in preventing fractures confirmed

Phentermine & Topiramate combination (Qnexa®) for obstructive sleep apnea (OSA)....

In continuation of my update on Qnexa® (combination of Phentermine & Topiramate), a drug by VIVUS, Inc., I found this info really interesting  to share with.

VIVUS, Inc on 7. January 201, announced positive results from a phase 2 study evaluating the safety and efficacy of Qnexa®, an investigational drug, for the treatment of obstructive sleep apnea (OSA). VIVUS recently completed phase 3 development of Qnexa for the treatment of obesity and submitted a New Drug Application (NDA) to the FDA for that indication. The OSA- study announced  demonstrated statistically significant improvement in the apnea/hypopnea index ("AHI" - a measure of the severity of sleep apnea) in patients with OSA treated with Qnexa for 28 weeks.

OSA is a sleep-related breathing disorder that involves a decrease or complete halt in airflow despite an ongoing effort to breathe. OSA is associated with an increased risk of hypertension, diabetes, stroke, sudden cardiac death and all-cause mortality. Currently, there are no approved pharmacologic treatments for OSA and current treatment approaches are limited to devices or surgery, so if approved by the FDA, Qnexa®  not only reduce the weight  but also significantly improve sleep apnea.

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=434708

NDA of Lurasidone for Schizophrenia...

In continuation of my update on  Lurasidone, ........

Dainippon Sumitomo Pharma America, Inc. (DSPA), a U.S. subsidiary of Dainippon Sumitomo Pharma Co., Ltd. (DSP), submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for lurasidone, an investigational atypical antipsychotic agent for the treatment of schizophrenia. The application, submitted on December 30, 2009, includes data from more than 40 clinical studies involving more than 2,500 lurasidone-treated patients.The efficacy of once-daily lurasidone was demonstrated in four six-week, placebo-controlled studies, involving hospitalized patients with schizophrenia. These studies included the global PEARL 1 and PEARL 2 clinical trials....

Ref : http://dsp-america.com/pdf/news/Lurasidone_NDA_Submission_PR_Jan_2010.pdf

Clorgyline an old antidepressant may reverse heart failure....

We know that Clorgyline is an irreversible and selective  inhibitor of monoamine oxidase A (MAO-A) . It is structurally related to pargyline (which is a preferential inhibitor of MAO type B) and when compared the antidepressant activity clorgyline is superior over Pargyline. However the drug is no longer in use in humans. 

Interestingly, now researchers from Johns Hopkins and other researchers have found in animal experiments that this  antidepressant developed over 40 years ago,  can blunt and even reverse the muscle enlargement and weakened pumping function associated with heart failure. Italian heart experts describes in a dozen key laboratory experiments in rodents how the  clorgyline,  blocks the action of enzyme monoamine oxidase-A (MAO-A) and stops its breakdown of a key neurohormone. Norepinephrine, as it is called, controls the pace of blood pumping and makes the heart pump harder and faster in response to stress.

This result is of great significance because of the fact that this is the first evidence showing how elevated MAO-A activity biochemically drives heart failure and that its dangerous downstream effects can be stalled by drug therapy. Hope this vicious chemical circle of stimulant norepinephrine overload and breakdown, might  offer  a disease blueprint with monoamine oxidase-A as the target for drugs similar to clorgyline to rein in the disease.

As claimed by the lead researcher Dr.Nazareno Paolocci, norepinephrine is not properly stored and released from the nerves directed to the heart, monoamine oxidase-A breaks it down, generating dangerous chemical species in the nerves and the heart muscle. and these toxic free radicals produce the same deleterious effects on heart muscle size and pumping function long observed in heart failure. Though further studies with similar class of compounds is essential  for this initial proof of an important principle, its a good achievement..

More details...

Celecoxib reduces the risk of common skin cancer in humans.....

We know that Celecoxib   is a non-steroidal anti-inflammatory drug (NSAID)  used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial adenomatous polyposis. It is marketed by Pfizer. It is known under the brand name Celebrex or Celebra for arthritis and Onsenal for polyps. Celecoxib is available by prescription in capsule form.

Researchers from UC-San Francisco and Children's Hospital Oakland,  (Dr. Tang was was an assistant professor at UC-San Francisco and Children’s Hospital Oakland  when the trial was conducted) have come up with very interesting results for the same drug. The drug can reduce the risk of a common skin cancer in humans. Though celecoxib, is associated with an increased risk of heart attack and stroke in some people, it's possible that topical application could have a safer, protective effect for people prone to developing the cancers, called basal cell carcinomas, the researcher believes.

For the current research, Tang and her colleagues capitalized on a previous finding suggesting that celecoxib, a NSAID, can inhibit the development of a different kind of skin cancer, squamous cell carcinoma, in mice. They wondered if the drug, sold by the pharmaceutical company Pfizer under the brand names Celebrex and Onsenal, would have a similar effect on the more common basal cell carcinoma.

Celecoxib is thought to work to prevent or slow cancer growth by interfering with the action of an enzyme called Cox-2, which causes tissue inflammation (pro inflammator). Celecoxib has both pain-killing (analgesic) and anti-inflammatory properties. Chronic inflammation has long been associated with the development of many types of cancer, and celecoxib has been shown in clinical trials to reduce the incidence of colon cancer in people with a genetic predisposition to the disease.

Interestingly, researchers stopped the clinical trials in 2003 (from 2001) when the study lead to high risk  of heart attack and stroke in patients taking a different NSAID. (Rofecoxib,  Vioxx by  Merck & Co. was withdrawn from the market by Merck in 2004  and Tang's trial was discontinued that year in response to ongoing concerns about long-term treatment with Cox-2 inhibitors). At that time, most participants had received about two years of drug treatment. No patient died or suffered adverse cardiovascular events due to their participation in the trial. Although drug treatment had been discontinued, the researchers continued to monitor basal cell carcinoma formation in people who had received the drug or placebo for an additional year to complete the three-year study. They found that, although both groups continued to develop new cancers during the study, oral celecoxib treatment decreased the growth of skin tumors by about 50 percent as compared to placebo in participants who entered the trial with 15 or fewer basal cell carcinomas. Celecoxib treatment also reduced the overall tumor burden in the  group of patients (where in the carcinomas are removed upon diagnosis in most people).

Now the lead researcher Dr. Tang is continuing her focus on skin cancer prevention at Stanford. She's currently investigating whether it's possible to develop a topical formulation of the drug that can be applied directly to the skin to achieve a similar protective effect without associated cardiovascular risk. Hope she will get positive results via topical formulation .....

In my opinion  its really a great achievement.We know that compounds with selective inhibitors of 5-LO (Lipoxygenase) and COX (Cyclooxegenase, that too COX-II) will be  the best NSAIDs without any ulcerogenecity, its good see that the  same compounds can be used to treat skin cancer....

Ref : http://med.stanford.edu/ism/2010/january/tang.html

Talampanel has potential to slow the muscle weakening that comes with amyotrophic lateral sclerosis (ALS)...

Talampanel (strutcure, source:ChemSpider), (8R)-7-Acetyl-5-  (4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine  is a drug used to treat epilepsy. Now researchers from Johns Hopkins and Indiana University, have found interesting activity of the same anticonvulsant drug, i.e., the drug has potential to slow the muscle weakening that comes with amyotrophic lateral sclerosis (ALS)  . The researchers after completing a Phase II clinical trial-an early, small-scale test to show if the drug works and continues to be safe. As per the claim by the researchers,  the drug talampanel showed some ability to slow the loss of major daily life activities such as speaking, walking and dressing that typically slip away as the disease progresses. Interestingly the drug  has the anti-anxiety and  muscle relaxing activity too (work in the brain and spinal cord).

The trial in 59 volunteers with ALS - also called Lou Gehrig's disease - showed that talampanel can be safe for patients with the disease and that any recorded side effects are tolerable.  Phase II trials are designed to show on a small scale if a drug is safe and if it works. So the present trial included ways to measure the drug's benefits, which came across as clear, if not statistically significant. The research demonstrates that talampanel appears able to slow the progression of disabling ALS symptoms. Though the effect isn't overwhelming at the dosage of medicine used in this early, very small trial and the researchers claims that  having promising human data is reason enough to keep it in the drug pipeline where they can really find out where it stands for patient.

With the exception of riluzole, the single FDA-approved drug for the disease, there's no other treatment to slow or stop it. Riluzole can extend life only modestly and hasn't been shown to slow ALS symptoms. so the need for better therapy is real. Hope in the days to come people with ALS symptoms will have a better drug...

Ref : http://www.hopkinsmedicine.org/Press_releases/2010/01_04a_10.html

Scientists determine how RNAi, a biological response to RNA, can regulate gene expression

Scientists determine how RNAi, a biological response to RNA, can regulate gene expression

New key factor (ßCTF, a small protein found in APP) identified in the development of Alzheimer's disease...

Inheritance of an extra copy of the gene- β -amyloid precursor protein, APP, in individuals with Down syndrome leads to the inevitable development of early onset Alzheimer's disease, known to be linked to the deposition of Amyloid β peptide or Aβ in the brain. However, a new study published online by Proceedings of the National Academy of Sciences identifies βCTF, a small protein found in APP, as a novel factor for the development of Alzheimer's disease related endosome abnormalities, which have also been tied previously to the loss of brain cells in Alzheimer's disease.

In their study, using the cells from individuals with Down syndrome that are genetically predisposed to developing Alzheimer's disease, the researchers showed that elevated levels of ßCTF, independent of Aß, cause a specific pattern of endosome defects with similar pathology of brain cells in Alzheimer's disease. As per the claim by Dr. Ying Jiang, (Department of Psychiatry at NYU Langone Medical Center. they were successfully able to pinpoint that ßCTF causes Alzheimer's disease-related endosome defects and successfully reverse these endosome defects by lowering ßCTF levels in the cells. Hope this study demonstrating an alternative protein factor, ßCTF, derived from the gene APP, is also unequivocally involved in Alzheimer's disease and may be of additional importance for the development of future effective therapies in the days to come...

Cladribine-the first oral disease-modifying multiple sclerosis therapy ?

In my earlier blog, I have mentioned about the NDA (new drug application) of this drug Cladribine as drug to treat Multiple Sclerosis.  Now as per the report by Decision Resources, one of the world's leading research and advisory firms for pharmaceutical and healthcare issues, finds that a recent "refuse to file" (RTF) letter issued by the FDA regarding Merck Serono's oral cladribine has heightened the competition between oral cladribine and its primary competitor, Novartis/Mitsubishi Tanabe's FTY-720 (fingolimod), to be the first oral disease-modifying multiple sclerosis therapy to reach the market in the United States.

Although oral cladribine's first-to-market advantage over FTY-720 will be reduced as a result of a likely delay to market caused by the FDA's action, oral cladribine is still expected to launch in the U.S. in 2010 while FTY-720 remains on track to launch in early 2011. .....

Ref : http://www.decisionresources.com/News-and-Events/Press-Releases/Multiple-Sclerosis-010510

Imetelstat (GRN 163L) shows promising results against brain cancer glioblastoma and prostate cancer...

In continuation of my update on Telomerase inhibitors, I find this info really interesting and hence sharing here with. As mentioned in my earlier blog about imetelstat (GRN163L )  has been undergoing Phase I clinical trials designed to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination, in solid tumors, chronic lymphoproliferative disease, multiple myeloma, lung and breast cancers and the company claims that Phase I objectives for imetelstat  (structure) have been achieved. Now  Dr. Jerry Shay, professor of cell biology of  The University of Texas Southwestern Medical Center at Dallas, claims that the same drug shows promise in fighting the brain cancer glioblastoma and prostate cancer.

Glioblastomas are the most common malignant brain tumors in adults, according to the American Cancer Society. They are difficult to treat with drugs because blood vessels in the brain have tightly constructed walls that allow only a few substances to pass through.

The researcher focused on cells called tumor-initiating cells. Some researchers believe that tumors contain a small subset of initiating cells – or cancer stem cells – that are able to initiate and drive tumors and that are often resistant to radiation therapy and chemotherapy.

In the glioblastoma study, Dr. Shay and his colleagues found that imetelstat blocked the action of telomerase in isolated tumor-initiating cells as well as the bulk of the tumor cells, eventually killing the cells. Combining imetelstat with radiation and a standard chemotherapy drug made imetelstat even more effective. When the researchers implanted human tumor-initiating cells into rodents, they found that imetelstat was able to enter brain tissue and inhibit telomerase activity.

In the prostate cancer study, the researchers isolated tumor-initiating cells from human prostate cancer cells. The cells showed significant telomerase activity. Imetelstat blocked the enzyme’s activity, and telomeres shortened greatly. As per Dr.Shay, since the drug attacks a mechanism that is active in most cancers, it might prove to be widely useful, especially when combined with other therapies.

Hope  Geron people must be really happy for these results  and conclusions.....

Ref : http://www.utsouthwestern.edu/utsw/cda/dept353744/files/570509.html