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

Liquorice root for antibiotic-resistant infections resulting from severe burns...

Liquorice root candy, or properly Glycyrrhiza glabra, is the dried root  of the liquorice plant (see pictures - credit : wikipedia), which is eaten as a candy. It is also used in traditional Chinese medicine, as well as in the traditional medicines of Japan, Korea, Vietnam, and other Asian nations (In India ಯಷ್ಠಿಮಧು/ಅತಿಮಧುರ (in kannada & मुलहठी in hindi). The extract of the liquorice root is one of the main ingredients in liquorice confectionery. Liquorice root can be shredded and added to boiling water to create liquorice root tea. Liquorice root has been traditionally used as a herbal remedy against different symptoms, such as cough and catarrh. People with heart conditions or high blood pressure should avoid ingesting extensive amounts of liquorice, as it can further heighten blood pressure and lead to stroke.

Though liquorice root has also been reported to speed the healing of canker sores, now researchers from University of Texas Medical Branch and Shriners Hospitals for Children have come up with more interesting findings, that is root can be used to treat antibiotic-resistant infections resulting from severe burns. They found that in burned mice, glycyrrhizin improved the ability of damaged skin to create small proteins that serve as the first line of defense against infection. These proteins, called antimicrobial peptides, work by puncturing the cell membranes of bacteria similar to how pins pop balloons. As per the claim by the researchers lead by Dr. Fujio Suzuki, more research is necessary to determine if this finding would have any implications for people with cystic fibrosis, who can develop Pseudomonas aeruginosa infections in their lungs.

Ref : http://www.jleukbio.org/cgi/content/abstract/87/1/35

Donepezil hydrochloride for Dementia Related to Alzheimer's Disease...

We know that, ARICEPT® [donepezil hydrochloride, see structure  (source-chemSpider) ] is a reversible inhibitor of the enzyme acetylcholinesterase, known chemically as (±)-2,3-dihydro-5,6-dimethoxy-2 -[[1-(phenylmethyl)-4-piperidinyl]- methyl]-1H-inden-1-one hydrochloride. Donepezil hydrochloride is commonly referred to in the pharmacological literature as E2020.

Acetylcholinesterase is the target of many Alzheimer's Dementia drugs , nerve gases, particularly the organophosphates (e.g. Sarin) and insecticides (e.g. carbaryl). These agents — known as cholinesterase inhibitors — block the function of acetylcholinesterase and thus cause excessive acetylcholine to accumulate in the synaptic cleft. The excess acetylcholine causes neuromuscular paralysis (i.e. interminable muscle contractions) throughout the entire body, leading to death by asphyxiation.

The U.S. Food and Drug Administration approved the first generic versions of Aricept (donepezil hydrochloride) orally disintegrating tablets on Dec. 11. Donepezil hydrochloride is indicated for the treatment of dementia related to Alzheimer's disease. Orally disintegrating tablets dissolve on the tongue, without having to be swallowed whole. This may make it easier to take the medication for older or disabled patients who have difficulty swallowing.

Alzheimer's disease :

Alzheimer's disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually, the ability to carry out the simplest tasks of daily living. In most people with Alzheimer's disease, symptoms first appear after age 60. Alzheimer's disease is the most common cause of dementia among older people, but it is not a normal part of aging...

Ref : http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm194173.htm

Quetiapine fumarate (Seroquel XR) for Major Depressive Disorder (MDD)....

Quetiapine fumarate (see structure) is marketed by AstraZeneca as Seroquel or SeroquelXR and by Orion Pharma as Ketipinor, is an atypical antipsychotic schizophrenia used in the management of, bipolar I mania, bipolar II depression, bipolar I depression, and used off-label for a variety of other purposes, including insomnia and anxiety disorders.

It is sometimes used off-label, often as an augmentation agent, to treat such conditions as obsessive-compulsive disorder, post-traumatic stress disorder, restless legs syndrome, autism, alcoholism, depression, Tourette syndrome, and has been used by physicians as a sedative for those with sleep disorders or anxiety disorders.

Astra-Zeneca, recently  announced that the FDA has approved once-daily Seroquel XR (quetiapine fumarate) Extended Release Tablets as adjunctive (add-on) treatment to antidepressants in adults with Major Depressive Disorder (MDD). Seroquel XR is the only medication in its class approved by the FDA to treat both major depressive disorder as adjunctive therapy and acute depressive episodes associated with bipolar disorder as monotherapy. The company claims that this approval for Seroquel XR provides physicians with a new adjunctive treatment option for patients with MDD who have an inadequate response to their current antidepressant. FDAs approval of Seroquel XR is based on a clinical development program in MDD involving 939 patients randomized across two studies that assessed the efficacy and safety of once-daily treatment with Seroquel XR as adjunctive treatment to antidepressants.....

Ref : http://www.astrazeneca.com/media/latest-press-releases/2009/seroquel-us-MDD?itemId=7660757

Dabigatran etexilate a better drug than warfarin for VTE?.

We know that Dabigatran is an anticoagulant from the class of the direct thrombin inhibitors. It is being studied for various clinical indications and may replace warfarin as the preferred anticoagulant in many cases. It is orally administered as the prodrug dabigatran etexilate (marketed as Pradaxa since April 2008 in European countries and Pradax in Canada). It was developed by the pharmaceutical company Boehringer Ingelheim.

Now researchers lead by  Dr. Sam Schulman, a professor of medicine of the Michael G. DeGroote School of Medicine (McMaster University), who conducted a randomized, double-blind trial of 2,539 patients with acute VTE (venous thromboembolism) have found that dabigatran (see structure) is a safe and effective anticoagulant that does not require the routine monitoring or dose adjustments that are necessary with warfarin. In other words, patients can receive the same results in a more convenient manner. 

As per the claim by the researchers, the improvement seen in both groups from the treatments was similar. After six months of treatment, only 2.4 percent of the dabigatran etexilate group (30 patients) and 2.1 percent of the warfarin group (27 patients) experienced recurrent VTE. The safety of the two drugs was also comparable. In the dabigatran etexilate arm, 205 patients experienced bleeding (including 20 patients with major bleeding) versus 277 patients in the warfarin arm (including 24 with major bleeding). Other possible side effects, including death, acute coronary syndromes, and abnormalities in liver function tests, were infrequent in the two groups. Hope patients suffering from VTE will now breathe a sigh of relief....

Ref : http://dailynews.mcmaster.ca/story.cfm?id=6511

Engineered tobacco plants have more potential as a biofuel

Engineered tobacco plants have more potential as a biofuel

New RNA interference technique can silence up to five genes

New RNA interference technique can silence up to five genes

Nonanal (odour produced in humans and birds) - an attractant for the Culex mosquito ?

In continuation of my update on developments in mosquito repellents,  I  found this  interesting info. In  my earlier blog, I mentioned that carbon dioxide   emitted in human  breath  is  the main  attractant  for the    Culex mosquito to find people, aiding the transmission of these deadly diseases. Now scientists from University of California, Davis, have identified the dominant odor naturally produced in humans and birds that attracts the blood-feeding Culex mosquitoes, which transmit West Nile virus and other life-threatening diseases. As per the claim by the researchers, Nonanal (nonanaldehyde or pelargonaldehyde see below structure) is the powerful semiochemical that triggers the mosquitoes' keen sense of smell, directing them toward a blood meal. A semiochemical is a chemical substance or mixture that carries a message.The antennae of the Culex quinquefasciatus are highly developed to detect even extremely low concentrations of nonanal. Mosquitoes detect smells with the olfactory receptor neurons of their antennae.

The UC Davis researchers tested hundreds of naturally occurring compounds emitted by people and birds. They collected chemical odors from 16 adult human subjects, representing multiple races and ethnic groups. More interestingly, Leal and Syed found that nonanal acts synergistically with carbon dioxide, a known mosquito attractant.  Nonanal, in combination with carbon dioxide, increased trap captures by more than 50 percent, compared to traps baited with carbon dioxide alone. Hope this discovery will help those searching for cheaper, environment friendly  repellents.

Ref : http://www.news.ucdavis.edu/search/news_detail.lasso?id=9289 

Oleanolic acid capsules for Hepatitis B......

We  know that Oleanolic acid is a naturally occurring triterpenoid, widely  distributed in food and medicinal plants, related to betulinic acid. It can be found in Phytolacca americana (American pokeweed), and Syzygium spp, garlic, etc. It is relatively non-toxic, antitumor, and hepatoprotective (antihepatotoxic - protecting liver cells against toxins) as well as exhibiting antiviral properties.

Oleanolic acid was found to exhibit strong anti-HIV activity, the related compound betulinic acid was used to create the first commercial maturation inhibitor drug. It was first studied and isolated from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phordendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). Other Syzygium species including java apple (Syzygium samarangense) and rose apples contain it.

Now Biostar Pharmaceuticals, Inc. has completed preparation to launch its flagship Xin Aoxing Oleanolic Acid ("Xin Aoxing") Capsules for the treatment of Hepatitis B in Beijing and Shanghai in early January 2010.....

Ref : http://www.biostarpharmaceuticals.com/newsdisp.asp?id=78

Happy New Year 2010

Wishing one and all a happy, prosperous and peaceful new year 2010...

Dr.Umesh




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Combination of Phentermine & Topiramate for obesity treatment......

We know that Phentermine (see structure) is  an appetite suppressant of the  amphetamine and phenethylamine class. It is approved as an appetite suppressant to help reduce weight in obese patients. Its  usually used for short-term and in combination with exercise, diet and behavioral modification. Is typically prescribed for individuals, who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.  

Mode of action : Phentermine, in doses clinically used, works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter or chemical messenger that signals a fight-or-flight response, reducing hunger. Phentermine works outside the brain as well to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction. At high doses, phentermine releases serotonin and dopamine as well, but such doses are never used in clinical medicine.  

Topiramate (structure below), is a known anticonvulsant agent and  also  reported  for  the  treatment   of

SSRI-  induced weight gain in anxiety disorders. However a combination   of these two drugs (Phentermine & Topiramate) has been  tried by VIVUS, Inc. and has submitted New Drug Application (NDA)   to the U.S. Food and Drug Administration (FDA) seeking approval of Qnexa (Phentermine & Topiramate combination) - its investigational drug for the treatment of obesity, including weight loss and maintenance of weight loss, in patients who are obese or overweight with co-morbidities such as hypertension, type 2 diabetes, dyslipidemia or central adiposity.

The NDA submission follows the successful completion of the phase 3 program for Qnexa, including the recently announced results from the two pivotal, year-long phase 3 studies (EQUIP and CONQUER). In these trials, patients treated with all three doses of Qnexa achieved significant percent and categorical weight loss compared to placebo and met regulatory requirements for weight loss products as defined in the current FDA Guidance for Developing Products for Weight Management. Patients treated with Qnexa also had significant dose-related improvements in a variety of secondary endpoints including reductions in cardiovascular and metabolic risk factors. Hope people with obesity, will breathe a sigh of relief in the near future....

Ref : http://ir.vivus.com/releasedetail.cfm?ReleaseID=433172