Watermelon juice relieves post-exercise muscle soreness

Encarna Aguayo and colleagues cite past research on watermelon juice's antioxidant properties and its potential to increase muscle protein and enhance athletic performance. But scientists had yet to explore the effectiveness of watermelon juice drinks enriched in L-citrulline. Aguayo's team set out to fill that gap in knowledge.

They tested natural watermelon juice, watermelon juice enriched in L-citrulline (ABOVE STRUCTURE) and a control drink containing no L-citrulline on volunteers an hour before exercise. Both the natural juice and the enriched juice relieved muscle soreness in the volunteers. L-citrulline in the natural juice (unpasteurized), however, seemed to be more bioavailable -- in a form the body could better use, the study found.

Watermelon juice relieves post-exercise muscle soreness

Combined therapy could repair and prevent damage in Duchenne muscular dystrophy, study suggests

Results from a clinical trial of eteplirsen, {RNA, [P-deoxy-P-(dimethylamino)](2',3'-dideoxy-2',3'-imino-2',3'-seco)(2'a→5')(C-m5U-   C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G),    5'-[P-[4-[[2-[2-(2-hydroxyethoxy) ethoxy]ethoxy] carbonyl]-1-piperazinyl]-N,N-   dimethylphosphonamidate]}  a drug designed to treat Duchenne muscular dystrophy, suggest that the therapy allows participants to walk farther than people treated with placebo and dramatically increases production of a protein vital to muscle growth and health. The study, led by a team in The Research Institute at Nationwide Children's Hospital, is the first of its kind to show these results from an exon-skipping drug -- a class of therapeutics that allows cells to skip over missing parts of the gene and produce protein naturally....

Combined therapy could repair and prevent damage in Duchenne muscular dystrophy, study suggests

Ref http://onlinelibrary.wiley.com/doi/10.1002/ana.23982/abstract

New approach in the treatment of breast cancer

Scientists at the MedUni Vienna, in collaboration with a working group led by Nancy Hynes at the University of Basel, have discovered a new approach in the treatment of breast cancer: an international team involving the Clinical Institute of Pathology at the MedUni Vienna has been able to demonstrate the activation of a receptor, the Ret protein (Rearranged during transfection), on the surface of breast cancer cells. Increased levels of this protein are associated with a lower likelihood of survival for breast cancer patients.

Ref : http://onlinelibrary.wiley.com/doi/10.1002/emmm.201302625/abstract

Read more about RET Inhibitors at : http://www.cancercommons.org/tag/ret-inhibitors/

New approach in the treatment of breast cancer

GLENMARK-A new way for a new world « New Drug Approvals

Undiminished zest..

“Every year we expect two more molecules to get into clinical trials,” says Saldanha, his zest undiminished by past failures. “In 2008, in a span of one or two quarters, our entire pipeline pretty much got wiped out, but we never lost our commitment and passion.” At that time its most advanced molecule, oglemilast, used for treating patients with chronic obstructive pulmonary disease, had to be abandoned when its Phase IIb trials produced unsatisfactory results. It also had to suspend clinical development of GRC 6211, a compound for treating osteoarthritis pain, because of side effects.

GLENMARK-A new way for a new world « New Drug Approvals

New treatment for brittle bone disease found

We know that, Risedronic acid (see structure) (INN) or risedronate sodium (USAN) is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget's disease of bone. It is produced and marketed by Warner Chilcott, Sanofi-Aventis, and in Japan by Takeda under the trade names Actonel, Atelvia, and Benet. It is also available in a preparation that includes a calcium carbonate supplement, asActonel with Calcium.

Osteogenesis imperfecta (OI and sometimes known as brittle bone disease, or "Lobstein syndrome") is a congenital bone disorder. People with OI are born with defective connective tissue, or without the ability to make it, usually because of a deficiency ofType-I collagen. This deficiency arises from an amino acid substitution of glycine to bulkier amino acids in the collagen triple helixstructure. The larger amino acid side-chains create steric hindrance that creates a bulge in the collagen complex, which in turn influences both the molecular nanomechanics as well as the interaction between molecules, which are both compromised.^[3] As a result, the body may respond by hydrolyzing the improper collagen structure. If the body does not destroy the improper collagen, the relationship between the collagen fibrils and hydroxyapatite crystals to form bone is altered, causing brittleness.^[4] Another suggested disease mechanism is that the stress state within collagen fibrils is altered at the locations of mutations, where locally larger shear forces lead to rapid failure of fibrils even at moderate loads as the homogeneous stress state found in healthy collagen fibrils is lost.^[3]These recent works suggest that OI must be understood as a multi-scale phenomenon, which involves mechanisms at the genetic, nano-, micro- and macro-level of tissues.

Ref : http://linkinghub.elsevier.com/retrieve/pii/S0140673613610910

New treatment for brittle bone disease found

New role for Tamoxifen in saving high-risk breast cancer patients

In continuation of my update on Tamoxifen...

New role for Tamoxifen in saving high-risk breast cancer patients

Ref : http://jco.ascopubs.org/content/early/2013/08/05/JCO.2012.47.8313

New designer compound JQ1, treats heart failure by targeting cell nucleus

Researchers from Case Western Reserve University School of Medicine and the Dana-Farber Cancer Institute have made a fundamental discovery relevant to the understanding and treatment of heart failure -- a leading cause of death worldwide. The team discovered a new molecular pathway responsible for causing heart failure and showed that a first-in-class prototype drug, JQ1, (see structure)  blocks this pathway to protect the heart from damage.

In contrast to standard therapies for heart failure, JQ1 works directly within the cell's command center, or nucleus, to prevent damaging stress responses. This groundbreaking research lays the foundation for an entirely new way of treating a diseased heart. The study is published in the August 1 issue of Cell.

"As a practicing cardiologist, it is clear that current heart failure drugs fall alarmingly short for countless patients. Our discovery heralds a brand new class of drugs which work within the cell nucleus and offers promise to millions suffering from this common and lethal disease," said Saptarsi Haldar, MD, senior author on the paper, assistant professor of medicine at Case Western Reserve and cardiologist at University Hospitals Case Medical Center.

Heart failure occurs when the organ's pumping capacity cannot meet the body's needs. Existing drugs, most of which block hormones such as adrenaline at the cell's outer surface, have improved patient survival. Unfortunately, several clinical studies have demonstrated that heart failure patients taking these hormone-blocking drugs still succumb to high rates of hospitalization and death. Leveraging a new approach, the research team turned their attention from the cell's periphery to the nucleus -- the very place that unleashes sweeping damage-control responses which, if left unchecked, ultimately destroy the heart.

The team found that a new family of genes, called BET bromodomains, cause heart failure because they drive hyperactive stress responses in the nucleus. Prior research linking BET bromodomains to cancer prompted the laboratory of James Bradner, MD, the paper's senior author and a researcher at the Dana-Farber, to develop a direct-acting BET inhibitor, called JQ1. In models of cancer, JQ1 functions to turn off key cancer-causing genes occasionally prompting cancer cells to "forget" they are cancer. In models of heart failure, JQ1 silences genetic actions causing enlargement of and damage to the heart even in the face of overwhelming stress.

"While it's been known for many years that the nucleus goes awry in heart failure, potential therapeutic targets residing in this part of the cell are often dubbed as 'undruggable' given their lack of pharmacological accessibility," said Jonathan Brown, MD, cardiologist at Brigham and Women's Hospital and co-first author on the paper. "Our work with JQ1 in pre-clinical models shows that this can be achieved successfully and safely."

Ref : http://www.sciencedirect.com/science/article/pii/S0092867413008842

Video : http://www.ted.com/talks/jay_bradner_open_source_cancer_research.html

New designer compound treats heart failure by targeting cell nucleus

Scripps Florida Scientists Devise New Way to Dramatically Raise RNA Treatment Potency

"We're trying to make tools that can target any RNA motif," said Matthew Disney, a TSRI associate professor who authored the research with a research associate in his lab, Lirui Guan. "This study completely validates our design -- it validates that our compound targets the desired RNA sequence in a complex cellular environment that contains many hundreds of thousands of RNAs."

While targeting DNA has been used as a therapeutic strategy against cancer, few similar approaches have been attempted for disease-associated RNAs.

In the new study, the scientists created a small molecule that binds to the genetic defect in RNA that causes myotonic dystrophy type 1 and improves associated defects in cell culture.

Myotonic dystrophy type 1 involves a type of RNA defect known as a "triplet repeat," a series of three nucleotides repeated more times than normal in an individual's genetic code. In this case, the repetition of the cytosine-uracil-guanine (CUG) in the RNA sequence leads to disease by binding to a particular protein, MBNL1, rendering it inactive and resulting in a number of protein-splicing abnormalities.

To achieve the increase in the drug candidate's potency, Disney and his colleagues attached a reactive molecule (a derivative of chlorambucil, (see structure below) a chemotherapy drug that has been used to treatment a form of leukemia) to the small molecule they had identified. As a result, the new compound not only binds to the target, it becomes a permanent part of the target -- as if it were super glued to it, Disney said. Once attached, it switches off the CUG defect and prevents the cell from turning it back on.

Disney was surprised at the approximately 2,500-fold improvement in potency with the new approach.

"I was shocked by the increase," he said. "This takes the potency into the realm where one would like to see if the compound were to have real therapeutic potential."

As a result, the new compound, known as 2H-4-CA, is the most potent compound known to date that improves DM1-associated splicing defects. Importantly, 2H-4-CA does not affect the alternative splicing of a transcript not regulated by MBNL1, demonstrating selectivity for the CUG repeat and suggesting that it might have minimal side effects. "We can now use this approach to attach reactive molecules to other RNA targeted small molecules," Disney said.

The reactive molecule model also provides a potentially general method to identify cellular targets of RNA-directed small molecules. Such probes could also identify unintended targets, information that could be used to design and identify compounds with improved selectivity in an approach similar to activity-based profiling, Disney said.

Scripps Florida Scientists Devise New Way to Dramatically Raise RNA Treatment Potency

Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain diseases

The UCLA researchers, led by David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of this technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer's and other degenerative diseases.

o identify natural and synthetic compounds that might prevent the aggregation and toxicity of amyloid fibrils. Such studies have revealed that polyphenols, naturally occurring compounds found in green tea and in the spice turmeric, can inhibit the formation of amyloid fibrils. In addition, several dyes have been found to reduce amyloid's toxic effects, although significant side effects prevent them from being used as drugs. 

Armed with a precise knowledge of the atomic structure of the amyloid-beta protein, Jiang, Eisenberg and colleagues conducted a computational screening of 18,000 compounds in search of those most likely to bind tightly and effectively to the protein.

Those compounds that showed the strongest potential for binding were then tested for their efficacy in blocking the aggregation of amyloid-beta and for their ability to protect mammalian cells grown in culture from the protein's toxic effects, which in the past has proved very difficult. Ultimately, the researchers identified eight compounds and three compound derivatives that had a significant effect.

While these compounds did not reduce the amount of protein aggregates, they were found to reduce the protein's toxicity and to increase the stability of amyloid fibrils  a finding that lends further evidence to the theory that smaller assemblies of amyloid-beta known as oligomers, and not the fibrils themselves, are the toxic agents responsible for Alzheimer's symptoms.

The researchers hypothesize that by binding snugly to the protein, the compounds they identified may be preventing these smaller oligomers from breaking free of the amyloid-beta fibrils, thus keeping toxicity in check...

Ref : http://elife.elifesciences.org/content/2/e00857

Scientists ID compounds that target amyloid fibrils in Alzheimer's, other brain diseases

GlaxoSmithKline receives CHMP positive opinion for REVOLADE

In continuation of my update on Eltrombopag

Eltrombopag (codenamed SB-497115-GR) is a medication that has been developed for conditions that lead to thrombocytopenia (abnormally low platelet counts). It is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of the hormone thrombopoietin. Eltrombopag was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals. Designated an orphan drugin the USA and European Union, it is being manufactured and marketed by GlaxoSmithKline under the trade name Promacta in the USA and will be marketed as Revolade in the EU. Eltrombopag was approved by the U.S. Food and Drug Administration on November 20, 2008....

GlaxoSmithKline receives CHMP positive opinion for REVOLADE

Rapamycin: Limited anti-aging effects

In continuation of my update on Rapamycin

The drug rapamycin is known to increase lifespan in mice. Whether rapamycin slows down aging, however, remains unclear. A team of researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Helmholtz Zentrum München has now found that rapamycin extends lifespan -- but its impact on aging itself is limited. The life-extending effect seems to be related to rapamycin's suppression of tumors, which represent the main causes of death in these mouse strains....

Ref : http://www.jci.org/articles/view/67674

Rapamycin: Limited anti-aging effects

Teduglutide offers relief for patients with short-bowel syndrome

 

In continuation of my update on Teduglutide

Teduglutide (brand names Gattex and Revestive) is a 36-membered polypeptide and glucagon-like peptide-2 analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion. In Europe it is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on December 21, 2012...

Teduglutide offers relief for patients with short-bowel syndrome

Chelsea Therapeutics Announces FDA Acceptance of Northera (droxidopa) NDA Resubmission

In continuation of my update on droxidopa.....

Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today announced that the U.S. Food and Drug Administration (FDA) has acknowledged receipt of the New Drug Application (NDA) resubmission seeking approval to market NORTHERA(TM) (droxidopa), an orally active synthetic precursor of norepinephrine, for the treatment of symptomatic neurogenic orthostatic hypotension (NOH) in patients with primary autonomic failure (Parkinson's disease, multiple system atrophy and pure autonomic failure), dopamine beta hydroxylase deficiency and non-diabetic autonomic neuropathy. The FDA has deemed the resubmission a complete response to its March 28, 2012 Complete Response Letter and assigned a new Prescription Drug User Fee Act (PDUFA) goal date of January 3, 2014.

Chelsea Therapeutics Announces FDA Acceptance of Northera (droxidopa) NDA Resubmission

Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults

Results of a two-year trial, led by Queen's scientist Professor Usha Chakravarthy, and published in The Lancet today (Friday 19 July), show that two drug treatments Lucentis and Avastinare equally effective in treating neovascular or wet age-related macular degeneration (wet AMD)....

Ref : http://www.sciencedirect.com/science/article/pii/S0140673613615019

Cheaper anti-cancer drug as effective as expensive drug in treating most common cause of blindness in older adults

New drugs to find the right target to fight Alzheimer's disease

A favorite Alzheimer's target: gamma secretase

The two next-generation classes of compound that are currently in clinical trials target an enzyme that cuts APP, known as gamma secretase. Until now, our understanding of the mechanism involved has been lacking. But with this work, the EPFL researchers were able to shed some more light on it by determining how the drug compounds affect gamma secretase and its cutting activity.

In most forms of Alzheimer's, abnormally large quantities of the long amyloid peptide 42 -- named like that because it contains 42 amino acids  are formed. The drug compounds change the location where gamma secretase cuts the APP protein, thus producing amyloid peptide 38 instead of 42, which is shorter and does not aggregate into neurotoxic plaques.

Compared to previous therapeutic efforts, this is considerable progress. In 2010, Phase III clinical trials had to be abandoned, because the compound being tested inhibited gamma-secretase's function across the board, meaning that the enzyme was also deactivated in essential cellular differentiation processes, resulting to side-effects like in gastrointestinal bleeding and skin cancer.

"Scientists have been trying to target gamma secretase to treat Alzheimer's for over a decade," explains Patrick Fraering, senior author on the study and Merck Serono Chair of Neurosciences at EPFL. "Our work suggests that next-generation molecules, by modulating rather than inhibiting the enzyme, could have few, if any, side-effects. It is tremendously encouraging."

Ref : http://www.nature.com/ncomms/2013/130802/ncomms3246/full/ncomms3246.html

New drugs to find the right target to fight Alzheimer's disease