Drug blocks light sensors in eye that may trigger migraine attacks

Panda and his collaborators turned to the Lundbeck library of diverse compounds. In hundreds of 384-well plates, a team led by Ken Jones at Lundbeck tested whether each chemical from the library turned off melanopsin by measuring the calcium levels after the plate was exposed to light. When melanopsin is functioning, calcium levels increase after light exposure indicating that light has been sensed and a signal is being generated. Several compounds from the chemical library stopped this calcium increase from happening, suggesting that they were blocking the function of melanopsin.

None of these compounds looked like retinoids, so it was an exciting breakthrough, Panda says. The chemicals, dubbed opsinamides (see structures a few), also 

showed no interaction with rhodopsin or other opsins. "We wanted to make sure they were specific to melanopsin," says Panda. To find out whether the opsinamides would have a physiological response in addition to binding to melanopsin in bench experiments, Megumi Hatori and Ludovic Mure from Panda's Salk lab group next looked at whether the drug affected the pupillary constriction in mice. Normally, in extremely bright light, the pupil of the eye shrinks to its smallest size. But when the mice were treated with one of the opsinamides, their pupils didn't shrink as usual. Most importantly, the drug had no detectable effect in mice lacking melanopsin, further showing its specificity for melanopsin. Finally, newborn mice treated with the compound no longer avoided bright lights. The results, Panda says, show that the drug is stopping melanopsin from signaling the brain when the eyes are exposed to bright light.

"So far, everything known about melanopsin has been discovered using knock-out mice that completely lack the receptor," says Panda. "So this offers a new way to study the protein." Kenneth Jones, the former project head at Lundbeck, notes that "the two compounds require further optimization in anticipation of clinical testing but are extraordinarily useful for research purposes and as leads in the discovery process." Co-author Jeffrey Sprouse has co-founded a start-up company, Cyanaptic, to do just that...

Ref : http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1333.html#figures

Drug blocks light sensors in eye that may trigger migraine attacks

Investigational oral regimen for hepatitis C shows promise

In a study of an all-oral drug regimen, a majority of volunteers with liver damage due to hepatitis C virus (HCV) infection were cured following a six-month course of therapy that combined an experimental drug, sofosbuvir, with the licensed antiviral drug ribavirin. The results showed that the regimen was highly effective in clearing the virus and well tolerated in a group of patients who historically have had unfavorable prognoses.

Investigational oral regimen for hepatitis C shows promise

Promising chronic pain drug developed

4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanol benzofuro[3,2-e]isoquinoline-7(7aH)-one (UMB 425)

Spotlighted in a recent issue of ACS Chemical Neuroscience, the compound, known as UMB 425, is as strong as morphine, but displays diminished tolerance over time with no obvious toxic effects.

"UMB 425 is a breakthrough in the development of therapeutics to treat chronic pain," says Coop. "Unlike other drugs developed to act on only one biological target, UMB 425 acts on two different opioid receptors in the body. When activated at the same time, these receptors work together to provide pain relief and slow the body's development of tolerance to the drug. This diminished tolerance allows a lower dose of the opioid to be administered for a longer time period, while still achieving the same level of pain relief."

For individuals living with chronic pain, either as a result of injury or disease such as arthritis, opioids are the standard treatment. But as the dosage increases to offset the body's tolerance to their effects, opioids cause a number of adverse effects, including constipation, nausea, drowsiness, and dizziness. The unique dual-profile of UMB 425 -- made possible through Coop's collaborations with Alexander MacKerell, PhD, professor in PSC and director of the School's Computer Aided Drug Design Center, and Maureen Kane, PhD, assistant professor in PSC and co-director of the School's Mass Spectrometry Facility -- provides both pain relief as well as diminished tolerance in one drug.

"Historically, medicinal chemists have developed drugs aimed at only one biological target," says Coop. "However, two drugs administered together have the potential to metabolize differently in different individuals, as well as affect patients' adherence to both drugs. A single compound that is able to provide both pain relief and diminished tolerance has the advantage of a defined ratio that we can optimize to ensure patients receive the maximum pain relief, while experiencing minimum adverse effects."

Ref : http://pubs.acs.org/doi/pdf/10.1021/cn4000428

Promising chronic pain drug developed

Eating whole fruits linked to lower risk of Type 2 diabetes

Eating more whole fruits, particularly blueberries, grapes, and apples, was significantly associated with a lower risk of type 2 diabetes, according to a new study led by Harvard School of Public Health (HSPH) researchers. Greater consumption of fruit juices was associated with a higher risk of type 2 diabetes. The study is the first to look at the effects of individual fruits on diabetes risk.

Eating whole fruits linked to lower risk of Type 2 diabetes

Unexpected use of former cancer drug, Zebularine...

Researchers at Lund University have unexpectedly discovered that an old cancer drug can be used to prevent rejection of transplanted tissue. The researchers now have high hopes that their discovery could lead to new treatments for both transplant patients and patients with autoimmune diseases.

"Our group were studying the effects of the old tumour drug Zebularine, (see structure) developed in the USA in the 1960s, and by chance we discovered that it had completely unexpected effects on the immune system," says Leif Salford, Senior Professor of Neurosurgery.

"It turned out that Zebularine has the ability to subdue the reaction of the body's immune system. This could be important in situations where tissue or organs are transplanted. We also think it could be used to curb the body's attacks on its own tissue in autoimmune diseases, for instance type 1 diabetes or rheumatoid arthritis," says Dr Nittby.

In studies on animals, the researchers used rats that were made diabetic. The researchers transplanted the islets of Langerhans  cell groups in the pancreas producing insulin -- from healthy rats from another kind of rat into those with diabetes. The diabetic rats were divided into two groups; one group were treated with Zebularine and the other, the control group, did not receive any treatment. The diabetic rats that were treated with Zebularine survived for a significantly longer period than the untreated rats.

"It is very interesting that we only treated them with Zebularine for two weeks, but the effects of the treatment could be observed throughout the 90-day follow-up period.

"The findings are very exciting and are a sign that the immune system was not just generally suppressed, but that the treatment was more targeted. Neither did we see any signs of side-effects," said Dr Nittby.

The researchers are now working intensively to further refine the treatment. The next step is to teach certain cells in the immune system -- the dendritic cells -- to accept certain specific proteins using the Zebularine treatment. This would mean that the treatment could be targeted even more.

Unexpected use of former cancer drug

Drug reduces hospitalizations and cost of treating young children with sickle cell anemia

The study is the largest ever focusing on the economic impact of the drug hydroxyurea (see structure below)

 in children with the inherited blood disorder. The result supports expanded use of the drug to extend the length and quality of life for sickle cell anemia patients of all ages, said Winfred Wang, M.D., a member of the St. Jude Department of Hematology and principal investigator of the multicenter federally funded trial known as BABY HUG.

"We estimate that hydroxyurea cut overall annual medical expenses about $3,000 for each patient by helping patients avoid disease complications that require inpatient hospital care," said Wang, who is first and corresponding author of the Pediatrics study. "We expect those savings will grow along with patients, whose symptoms often increase in severity and frequency as they age."

About 100,000 individuals in the U.S. and millions worldwide have sickle cell disease, which leaves them at risk for premature death and disability. The disease is the most common genetic disorder affecting African-American individuals, but those from other ethnic and racial backgrounds also inherit mutations in the hemoglobin gene. The mutations result in blood cells that are prone to assuming the sickled shape that gives the disease its name and that leave patients at increased risk for episodes of acute pain, stroke, organ damage and other complications.

Drug reduces hospitalizations and cost of treating young children with sickle cell anemia

Scientists fish for new epilepsy model and reel in potential drug

According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.

Scientists fish for new epilepsy model and reel in potential drug

Synthetic polymer could stop the spread of HIV

The researchers created the large molecule with several sugar molecules, known as glycopolymers (Glycopolymer is synthetic polymer with pendant carbohydrates). By using different sugars attached to the macromolecule in solution, the scientists were able to investigate which sugar molecules were the most effective in inhibiting the potential binding of the virus.

They then measured how the designed macromolecules compete with the virus to bind to the dendritic cells of the immune system at different concentrations.

"These are preliminary but encouraging results for potentially preventing the spread of the HIV by sexual contact," said Dr Remzi Becer from Queen Mary's School of Engineering and Materials Science.

"We've shown that our synthetic molecule binds to the immune cell, which in turn blocks the virus from attaching and entering. The precisely designed macromolecules could be an ingredient of a condom cream or vaginal gel to act as a physical barrier from allowing the virus into the body."

Dr Becer added: "While this isn't a cure for HIV, it is a novel approach that could dramatically slow down the spread of HIV by sexual contact, and a model that could be replicated to treat other sexually transmitted diseases."

Ref : http://onlinelibrary.wiley.com/doi/10.1002/marc.201300439/abstract

Synthetic polymer could stop the spread of HIV

Alzheimer's 'missing link' found: Promising target for new drugs

Yale School of Medicine researchers have discovered a protein that is the missing link in the complicated chain of events that lead to Alzheimer's disease, they report in the Sept. 4 issue of the journal Neuron. Researchers also found that blocking the protein with an existing drug can restore memory in mice with brain damage that mimics the disease.

Ref : http://dx.doi.org/10.1016/j.neuron.2013.06.036

Alzheimer's 'missing link' found: Promising target for new drugs

AstraZeneca and Bristol-Myers Squibb resubmit Dapagliflozin New Drug Application for the treatment of type 2 diabetes in the U.S

In continuation of my update on Dapagliflozin

AstraZeneca and Bristol-Myers Squibb resubmit Dapagliflozin New Drug Application for the treatment of type 2 diabetes in the U.S

FDA Advisory Committee Unanimously Recommends Approval Of Bayer's Riociguat In Two Pulmonary Hypertension Indications

We know that, Riociguat is (BAY 63-2521) is a novel drug that is in clinical development by Bayer. It is a stimulator ofsoluble guanylate cyclase (sGC). At the moment Phase III clinical trials investigate the use of riociguat as a new approach to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of a novel class of sGC stimulators.

FDA Advisory Committee Unanimously Recommends Approval Of Bayer's Riociguat In Two Pulmonary Hypertension Indications

Drug used for blood cancers may stop spread of breast cancer cells

In continuation of my update on Decitabine

A drug used to treat blood cancers may also stop the spread of invasive breast cancer, researchers at Mayo Clinic in Florida have discovered. Their study, published online in Breast Cancer Research, found that in the lab and in animals, the drug decitabine turns on a gene coding for protein kinase D1 (PRKD1) that halts the ability of cancer cells to separate from a tumor and spread to distant organs.

Drug used for blood cancers may stop spread of breast cancer cells

Ref : http://breast-cancer-research.com/content/15/2/R66

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

Data published in The Lancet showed that elderly people with Type 2 Diabetes (T2D) treated for 24 weeks with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin, marketed by Boehringer Ingelheim and Eli Lilly and Company, experienced significant reductions in blood glucose levels (HbA1c) compared with those receiving placebo. In addition, the overall safety and tolerability profile of linagliptin was similar to placebo, with no significant difference in hypoglycaemia.

Study: Type 2 diabetic patients treated with DPP-4 linagliptin experience reductions in blood glucose levels

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

Necrostatin-1 counteracts aluminum's neurotoxic effects

we know that, Necrostatin-1 inhibits necroptosis, a non-apoptotic cell death pathway. Inhibits the loss of mitochondrial membrane potential in TNFα-treated Jurkat cells (EC50=490 nM). Does not inhibit FAS-induced apoptosis and has no effect on apoptotic morphology. It displays a pronounced protective effect in a mouse model of ischemic brain injury and inhibits myocardial cell death. Inhibits RIP1 kinase the key upstream kinase involved in the activation of necroptosis (EC50=180nM).

Ivestigators have linked aluminum accumulation in the brain as a possible contributing factor to neurodegenerative disorders such as Alzheimer's disease. A new study published in Restorative Neurology and Neuroscience sheds light on the mechanism underlying aluminum-induced neuronal cell death and identifies necrostatin-1 as a substance which counteracts several of aluminum's neurotoxic effects.

Ref : http://iospress.metapress.com/content/h81617j3542x6487/?p=cfdaeabe671d4941ba8ae36ae55c6c5f&pi=0

Necrostatin-1 counteracts aluminum's neurotoxic effects