Monday, December 31, 2012

Chinese medicine yields secrets: Atomic mechanism of two-headed molecule derived from Chang Shan, a traditional chinese herb

The mysterious inner workings of Chang Shan  a Chinese herbal medicine used for thousands of years to treat fevers associated with malaria  have been uncovered thanks to a high-resolution structure solved at The Scripps Research Institute (TSRI). Described in the journal Nature this week, the structure shows in atomic detail how a two-headed compound derived from the active ingredient in Chang Shan works. Scientists have known that this compound, called halofuginone (a derivative of the febrifugine), can suppress parts of the immune system  but nobody knew exactly how.


The new structure shows that, like a wrench in the works, halofuginone jams the gears of a molecular machine that carries out "aminoacylation," a crucial biological process that allows organisms to synthesize the proteins they need to live. Chang Shan, also known asDichroa febrifuga Lour, probably helps with malarial fevers because traces of a halofuginone-like chemical in the herb interfere with this same process in malaria parasites, killing them in an infected person's bloodstream.


"Our new results solved a mystery that has puzzled people about the mechanism of action of a medicine that has been used to treat fever from a malaria infection going back probably 2,000 years or more," said Paul Schimmel, PhD, the Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry and member of The Skaggs Institute for Chemical Biology at TSRI. Schimmel led the research with TSRI postdoctoral fellow Huihao Zhou, PhD.

Halofuginone (see structure, below) has been in clinical trials for cancer, but the high-resolution picture of the molecule suggests it has a modularity that would make it useful as a template to create new drugs for numerous other diseases.





Gattex Approved for Short Bowel Syndrome - Drugs.com MedNews


We know that, Gattex (teduglutide) is a recombinant analog of human glucagon-like peptide 2 for the treatment of adults with short bowel syndrome....

Gattex Approved for Short Bowel Syndrome - Drugs.com MedNews

Sunday, December 30, 2012

FDA Approves Adasuve (loxapine) Inhalation Powder for the Acute Treatment of Agitation Associated with Schizophrenia or Bipolar I Disorder in Adults



We know that, Loxapine (LoxapacLoxitane) is a typical antipsychotic medication, used primarily in the treatment of schizophrenia. It is a member of the dibenzoxazepine class and structurally related to clozapine (which belongs to the chemically akin class of dibenzodiazepines). Several researchers have argued that Loxapine may behave as an atypical antipsychotic.  Loxapine may be metabolized by N-demethylation to amoxapine, a tetracyclic antidepressant. ........




Saturday, December 29, 2012

Penn Team Mimicking a Natural Defense Against Malaria to Develop New Treatments

Penn Team Mimicking a Natural Defense Against Malaria to Develop New Treatments

Dantrolene shows promise for treating DMD


 File:Dantrolene Tanaka et al.svg

We know that, Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegiacerebral palsy, or patients with multiple sclerosis), 3,4-methylenedioxymethamphetamine ("ecstasy") intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning. It is marketed by JHP Pharmaceuticals LLC as Dantrium (in North America) and Dantrolen (Europe).
  

Friday, December 28, 2012

Dantrolene shows promise for treating DMD



 File:Dantrolene Tanaka et al.svg



We know that, Dantrolene sodium is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegiacerebral palsy, or patients with multiple sclerosis), 3,4-methylenedioxymethamphetamine   ("ecstasy") intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning. It is marketed by JHP Pharmaceuticals LLC as Dantrium (in North America) and Dantrolen (Europe).
  

Wednesday, December 26, 2012

FDA Approves Varizig for Reducing Chickenpox Symptoms

FDA Approves Varizig for Reducing Chickenpox Symptoms :

Varizag : http://www.cangene.com/VariZIG

Abiraterone improves outcomes for prostate cancer prior to chemo

Vismodegib team wins Drug Discovery of the Year award

In continuation of my update on Vismodegib

Vismodegib team wins Drug Discovery of the Year award: The British Pharmacological Society proudly announces that its first annual Drug Discovery of the Year award has been won by the discovery team developing vismodegib for the treatment of basal cell carcinoma (a type of skin cancer).

Monday, December 24, 2012

New low-cost combined therapy shows promise against malaria

Molecular parasitologist Stephen Rich at the University of Massachusetts Amherst has led a research team who report a promising new low-cost combined therapy with a much higher chance of outwitting P. falciparum than current modes. He and plant biochemist Pamela Weathers at the Worcester Polytechnic Institute (WPI), with research physician Doug Golenbock at the UMass Medical School, also in Worcester, have designed an approach for treating malaria based on a new use of Artemisia annua, a plant employed for thousands of years in Asia to treat fever.

"The emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed," says UMass Amherst graduate student and lead author Mostafa Elfawal. Rich, an expert in the malaria parasite and how it evolves, adds, "We no sooner get the upper hand than the parasite mutates to become drug resistant again. This cycle of resistance to anti-malarial drugs is one of the great health problems facing the world today. We're hoping that our approach may provide an inexpensive, locally grown and processed option for fighting malaria in the developing world."
Currently the most effective malaria treatment uses purified extracts from the Artemisia plant as part of an Artemisinin Combined Therapy (ACT) regime with other drugs such as doxycycline and/or chloroquine, a prescription far too costly for wide use in the developing world. Also, because Artemisia yields low levels of pure artemisinin, there is a persistent worldwide shortage, they add.

The teams's thesis, first proposed by Weathers of WPI, is that locally grown and dried leaves of the whole plant, rich in hundreds of phytochemicals not contained in the purified drug, might be effective against disease at the same time limiting post-production steps, perhaps substantially reducing treatment cost. She says, "Whole-plant Artemisia has hundreds of compounds, some of them not even known yet. These may outsmart the parasites by delivering a more complex drug than the purified form."

Rich adds, "The plant may be its own complex combination therapy. Because of the combination of parasite-killing substances normally present in the plant (artemisinin and flavonoids), a synergism among these constituent compounds might render whole plant consumption as a form of artemisinin-based combination therapy, or what we're calling a 'pACT,' for plant Artemisinin Combination Therapy."


Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0052746

Sunday, December 23, 2012

Research | Research news | Fighting sleeping sickness with X-ray lasers

Using the world’s most powerful X-ray free-electron laser, an international team of researchers, including scientists of the Max Planck Institute for Medical Research in Heidelberg, has obtained new insight into the structure of a medicinally important protein that may serve as a blueprint for the development of drugs to fight sleeping sickness. Science magazine have chosen the experimental study as one of the top ten scientific breakthroughs of the year.

Saturday, December 22, 2012

Stroke drug kills bacteria that cause ulcers and tuberculosis


sc-223958

Now researchers  found that, a compound called ebselen (see structure) effectively inhibits the thioredoxin reductase system in a wide variety of bacteria, including Helicobacter pylori which causes gastric ulcers and Mycobacterium tuberculosis which causes tuberculosis. Thioredoxin and thioredoxin reductase proteins are essential for bacteria to make new DNA, and protect them against oxidative stress caused by the immune system. Targeting this system with ebselen, and others compounds like it, represents a new approach toward eradicating these bacteria.

Building on previous observations where ebselen has shown antibacterial properties against some bacteria, Holmgren and colleagues hypothesized that the bacteria sensitive to ebselen relied solely on thioredoxin and thioredoxin reductase for essential cellular processes. They investigated this by testing it on strains of E. coli with deletions in the genes for thioredoxin, thioredoxin reductase and the glutaredoxin system. They found that strains with deletions in the genes coding for glutaredoxin system were much more sensitive than normal bacteria. Researchers further tested ebselen againstHelicobacter pylori andMycobacterium tuberculosis, which both naturally lack the glutaredoxin system and are frequently resistant to many commonly used antibiotics, and found both to be sensitive to ebselen.

"As rapidly as these organisms evolve, we need new drugs sooner rather than later," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "The fact that these scientists have found a new target for killing some of the most resistant bacteria is great news, but the fact that we already have at least one drug which we could possibly use now makes the news even better."


Ref : http://www.fasebj.org/content/early/2012/12/17/fj.12-223305

Friday, December 21, 2012

New Blood Thinner May Help Prevent Leg Clots, Study Finds - Drugs.com MedNews

In continuation of my update on apixaban....

We know that, Apixaban (BMS-562247-01, tradename Eliquis) is an anticoagulant for the prevention of venous thromboembolism and venous thromboembolic events. It is a direct factor Xa inhibitor. Apixaban has been available in Europe since May 2012 and was approved for preventing venous thromboembolism after elective hip or knee replacement.[1] An FDA decision on apixaban for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation was expected on June 28, 2012, but was delayed. It is being developed in a joint venture by Pfizer and Bristol-Myers Squibb.

Thursday, December 20, 2012

Drug used to treat HIV might defuse deadly staph infections

We know that, Maraviroc (structure below, brand-named Selzentry, or Celsentri outside the U.S.) is an antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. It is also classed as an entry inhibitor. It also appeared to reduce graft-versus-host disease in patients treated with allogeneic bone marrow transplantation for leukemia, in a phase 1/2 study.

Now  researchers from  NYU School of Medicine  suggests that an existing HIV drug called maraviroc could be a potential therapy for Staphylococcus aureus, a notorious and deadly pathogen linked to hundreds of thousands of hospitalizations each year.

The discovery arose from a serendipitous finding that was a part of a collaborative study between Dr. Torres, a bacteriologist, and immunologist Derya Unutmaz, MD, associate professor of microbiology and pathology and medicine, whose laboratories are adjacent to each other. 
They focused on a receptor called CCR5 that dots the surface of immune T cells, macrophages, and dendritic cells. Sixteen years ago, researchers at NYU School of Medicine discovered that CCR5 is the receptor HIV uses to gain entry into T cells in order to replicate, spread, and cause an infection that can progress into AIDS.
That same receptor has now been found to be critical to the ability of certain strains of Staph to specifically target and kill cells with CCR5, which orchestrate an immune response against the bacteria. The scientists discovered that one of the toxins the bacterium releases, called LukED, latches on to CCR5 and subsequently punches holes through the membrane of immune cells, causing them to rapidly die. The LukED toxin belongs to a family of proteins called leukotoxins, encoded and produced by Staph to fight off the immune system's defenses.
Ref : http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11724.html


Drug used to treat HIV might defuse deadly staph infections

Wednesday, December 19, 2012

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic


In continuation of my update on Everolimus


Treatment with everolimus led to tumor regression and  gnificantly improved survival compared  with placebo in mice with established lymphomas. However,  all  of  these  mice  eventually  relapsed as a result   of the growth of lymphoma  cells  resistant to the effec ts  of everolimus.
"These data confirmed our hypothesis that mTORC1 inhibition could suppress Myc-driven tumor initiation and growth," said McArthur. "The surprise was found in how mTORC1 inhibition led to tumor regression. We had expected that it would trigger cancer cells to die by a cellular process known as apoptosis, but we found that this was not the case."
Detailed analysis of the tumors indicated that everolimus caused tumor regression by inducing cellular senescence.

According to McArthur, normal cells protect themselves when cancer-driving genes are switched on is by entering a state called senescence. When cancers develop, they have found ways to overcome this safeguard. "Our data indicate that one way in which cancers bypass senescence, in particular senescence induced by Myc, is through a signaling pathway involving mTORC1," he said.

Resistance to everolimus treatment in mice with established lymphomas was associated with loss of the function of p53, a protein known to help suppress tumor formation and growth.
"The loss of effectiveness of everolimus therapy against lymphoma cells deficient in p53 function has important clinical implications," said McArthur. "Everolimus could be a useful new string to the bow for clinicians treating patients with Myc-driven cancers, in particular B cell lymphomas, but that it would be helpful only to those patients with functional p53."

Ref : http://cancerdiscovery.aacrjournals.org/content/early/2012/12/13/2159-8290.CD-12-0404.abstract?sid=79f94616-1798-4c19-92c2-26e76ad12905 

Tuesday, December 18, 2012

Antidepressant could do double duty as diabetes drug, study shows

We know that, Paroxetine (also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin) is an antidepressant drug of the SSRItype. Paroxetine is used to treat major depression, obsessive-compulsive disorder, panic disorder, social anxiety, posttraumatic stress disorder and generalized anxiety disorder in adult outpatients.

Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline. Genericformulations have been available since 2003 when the patent expired.
In adults, the efficacy of paroxetine for depression is comparable to that of older tricyclic antidepressants, with fewer side effects and lower toxicity.  Differences with newer antidepressants are subtler and mostly confined to side effects. It shares the common side effects and contraindications of other SSRIs, with high rates of nausea, somnolence, and sexual side effects. Paroxetine is associated with clinically significant weight gain. Pediatric trials of paroxetine for depression did not demonstrate statistical efficacy better than placebo.

Now University of Texas Medical Branch at Galveston researchers have  discovered that the commonly used antidepressant drug paroxetine could also become a therapy for the vascular complications of diabetes...

"The future potential of this study is that we may be able to 'repurpose' paroxetine for the experimental therapy of diabetic cardiac complications," Szabo said. "We'll need to carefully characterize its safety profile in diabetic patients, but I think there's definite potential here."

Ref : http://diabetes.diabetesjournals.org/content/early/2012/12/03/db12-0789
Antidepressant could do double duty as diabetes drug, study shows

Monday, December 17, 2012

Pfizer, Ligand announce FDA acceptance of bazedoxifene/conjugated estrogens NDA

Pfizer Inc.  and Ligand Pharmaceuticals Incorporated recently,  announced that the United States Food and Drug Administration (FDA) accepted for review a New Drug Application (NDA) for bazedoxifene/conjugated estrogens (BZA/CE), a potential new medicine for non-hysterectomized women for the treatment of moderate-to-severe vasomotor symptoms (VMS) and vulvar and vaginal atrophy (VVA) associated with menopause, as well as the prevention of postmenopausal osteoporosis. The FDA Prescription Drug User Fee Act (PDUFA) date is October 3, 2013. 





Pfizer, Ligand announce FDA acceptance of bazedoxifene/conjugated estrogens NDA

Friday, December 14, 2012

ETA receptor antagonism reduces novel cardiovascular risk factors in patients with CKD



Blocking the receptor for proteins that constrict blood vessels reduces markers of heart-related problems in patients with chronic kidney disease (CKD), according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). 

Neeraj Dhaun, MD, PhD (University of Edinburgh, in Scotland) and his colleagues conducted a randomized, double-blind study in 27 patients with CKD to compare the effects of sitaxentan, nifedipine (a blood vessel relaxant), and placebo on kidney function, blood pressure, arterial stiffness, and various heart-related markers. Among the major findings after six weeks of treatment:

  • Placebo and nifedipine did not affect three markers of heart-related problems: blood levels of uric acid; blood levels of asymmetric dimethylarginine (ADMA), a blocker of NO production; and urine levels of endothelin-1.
  • Sitaxentan (see structure above) treatment led to statistically significant reductions in all three of these markers.
  • Sitaxentan reduced proteinuria (an excess excretion of protein in the urine) to a significantly greater extent than nifedipine. Proteinuria is an indicator of kidney dysfunction.
  • Nifedpine  (right structure below) and sitaxentan both reduced blood pressure to a similar extent.

"The current study shows, for the first time, that ETA receptor antagonism selectively lowers novel cardiovascular risk factors in patients with kidney disease independent of blood pressure. These effects were seen in patients already receiving optimal treatment," said Dr. Dhaun. "These findings suggest a potential role for ETA receptor antagonism in conferring additional longer-term cardiovascular and renal benefits in patients with kidney disease," he added.....

Wednesday, December 12, 2012

Drug offers alternative treatment strategy for insomnia


In continuation of my update on  suvorexant

The team, led by W Joseph Herring (Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, USA), studied the effects of the orexin receptor antagonist suvorexant in treating 254 people aged 18 to 64 years with moderately severe insomnia.

The participants were randomly assigned to take either suvorexant, at doses of 10, 20, 40, or 80 mg, or placebo for 4 weeks, after which they switched to the alternative treatment for a further 4 weeks.

Their sleep was monitored in a sleep laboratory on the first night of taking each treatment and again in the fourth week of each treatment.

Sleep efficiency, reflecting the time patients spent in bed at night asleep, was an average 66% (with an average total sleep time of 316 minutes) before treatment and improved by a significant 5.2% to 12.9% on the first night of treatment with suvorexant, compared with placebo.


Suvorexant (see structure)  treatment also resulted in patients experiencing 21 to 37 fewer minutes awake during the first night when compared with placebo.

The benefits of suvorexant were maintained over the 4 weeks of the study, with a significant 4.7% to 10.4% improvement in sleep efficiency, compared with placebo.

For both outcomes, the effect was dose-related and all doses were superior to placebo for improving sleep efficiency on night 1 and at the end of week 4. Dose-related effects were also seen for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). The researchers note that, overall, suvorexant was well tolerated. The most common adverse event associated with the drug was somnolence, which showed a dose-related increase.

But there was no consistent evidence of rebound insomnia or withdrawal effects after 4 weeks of treatment, or for next-day residual effects.

"This study provides evidence that suvorexant may offer a successful alternative strategy for treating insomnia," Herring said in a press statement.

Tuesday, December 11, 2012

New small molecule inhibitor could be a safe and first-line treatment for metastatic breast cancer

Mesupron® (see structure below) is a new small molecule inhibitor, taken as a pill, that inhibits the uPA system. The results from a recent phase II clinical study suggest that the drug could be a safe and first-line treatment that extends progression-free survival for metastatic breast cancer patients, when combined with the chemotherapeutic drug Capecitabine.

The study included 132 patients with metastatic breast cancer from 20 centers in five countries. In the trial, patients who took Mesupron combined with Capecitabine went without the return of disease for a median 8.3 months after the therapy. Patients who only took Capecitabine had a progression-free survival of 7.5 months.


"The combination of oral agents was convenient for and well tolerated by the patients," says Goldstein. "Plans for future studies are ongoing."

The drug was developed by WILEX, a German pharmaceutical company that focuses on the development of small molecule inhibitors and other new targeted cancer drugs designed to give patients treatment options with fewer side effects than traditional chemotherapy. In the Phase II study, Goldstein and her collaborators also investigated the safety and efficacy of the drug, as well as the objective response rate  the patient population who had no sign of disease after a specific amount of time.

Nine percent of the patients who received only Capecitabine had a complete objective response after 24 weeks. The objective response rate among the patients taking the combination therapy was nearly twice that, at 17 percent. The researchers also looked at different subgroups of participants to try to identify which patients might receive the most benefit from a combination therapy involving Mesupron. Among 109 Caucasian patients, the progression free survival was 7.5 months for patients who received Capecitabine alone, and 9.1 months for those who also received Mesupron.

The drug also showed a significant improvement for patients who had previously received treatment  before their disease became metastatic. In the subgroup of patients (n=95) who received adjuvant chemotherapy following the primary diagnosis of breast cancer, progression free survival improved from 4.3 months in the Capecitabine alone group to 8.3 months in the Mesupron combination group.....

Ref : http://www.fccc.edu/information/news/press-releases/2012/2012-12-07-SABC-Goldstein-WILEX.html

Monday, December 10, 2012

New antidepressant acts very rapidly and is long lasting

A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose.



The compound, called GLYX-13, (see the structure) is the result of more than two decades of work by Joseph Moskal, research professor of biomedical engineering at Northwestern's McCormick School of Engineering and Applied Science and director of the University's Falk Center for Molecular Therapeutics.


"Our study showed that this compound is capable of eliciting a robust and rapid antidepressant effect without the typical side effects seen with other drugs that also modulate the NMDA receptor," said Moskal, who is founder and chief scientific officer of the Evanston-based biotechnology company Naurex Inc., which conducted the clinical study.
GLYX-13 works by modulating the NMDA (N-methyl-D-aspartate) receptor in the brain, as do current NMDA receptor antagonists such as ketamine, but GLYX-13 does not have their serious and limiting side effects, such as hallucinations and schizophrenia-like effects. (An antagonist is a substance that inhibits the physiological action of another.)
The positive effects of GLYX-13 were evident within 24 hours and lasted an average of seven days. The effect size, a measure of the magnitude of the drug's antidepressant efficacy, at both these times after a single dose was nearly double the effect size seen with most other antidepressant drugs after four to six weeks of repeated dosing.
Side effects of GLYX-13 were mild to moderate and were consistent with those observed in subjects receiving a placebo.

GLYX-13 is a four-amino acid peptide that modulates one of a large family of glutamate receptors, the NMDA (N-methyl-D-aspartate) receptor, in the brain. NMDA receptors play a key role in regulating synaptic plasticity -- the quality of the connection between neurons -- and thus are important in regulating learning and memory functions.

GLYX-13 is administered intravenously. Moskal said Naurex also is working on an oral drug with similar properties and potential.

Moskal hopes that these positive GLYX-13 results and the research efforts of his team and colleagues will help shepherd in more research and grant support for studying the role of the glutamate-mediated processes in neuropsychiatric disorders...

Ref : http://www.nature.com/npp/journal/vaop/naam/abs/npp2012246a.html



Sunday, December 9, 2012

Severe morning sickness patients get relief from anti-seizure drug


 In continuation of my update on gabapentin

"The study showed that after two weeks of gabapentin therapy, the seven women experienced an average 80 percent reduction in their nausea and a 94 percent reduction in their vomiting and near normal levels of eating and drinking," Guttuso says. After this study was published, Guttuso knows of five more women with hyperemesis gravidarum that tried gabapentin and all experienced excellent relief.

The women needed to take gabapentin on average until about half way through their pregnancies before they could stop it without recurrent nausea and vomiting.

One of the potential concerns with gabapentin was that two of the babies born to patients in the UB study were found to have congenital defects. As a result, the Food and Drug Administration placed the study on clinical hold in April 2011 until further safety data was available on the use of gabapentin during pregnancy.

By May 2012 several pregnancy registries and other studies had reported that the rate of congenital defects among a total of 258 infants born to women taking gabapentin early in their pregnancies was about the same as the rate of congenital defects in the general population. After reviewing these findings, the FDA removed the clinical hold allowing Guttuso to resume his research on the effects of gabapentin on hyperemesis gravidarum. Although the results of the small pilot study were very encouraging, Guttuso emphasizes that a placebo-controlled study among many more patients needs to be conducted in order to know if gabapentin truly is effective for hyperemesis gravidarum. "The evidence right now is still very preliminary," he states.


Saturday, December 8, 2012

Lenalidomide offers an effective alternative treatment for cutaneus lupus erythematosus, study suggests

In continuation of my update on lenalidomide

A new study into the thalidomide derivative lenalidomide,  shows that treatment with lenalidomide is safe, with patients seeing an improvement in as little as two weeks. 


There have been several small scale clinical studies into the use of thalidomide for cutaneus lupus erythematosus,  CLE for the third of patients which do not respond to the standard therapy including steroids, antimalarials and immunosuppressive agents. Although thalidomide has a bad press because of its effects on embryonic development, properly administered it is an effective alternative treatment for several types of cancer and inflammatory conditions, albeit with severe side effects which can limit continuous use.

Lenalidomide has been suggested as a more potent, but less toxic, alternative, and previous studies on a small number of patients have had encouraging results. In order to examine the efficacy of lenalidomide more thoroughly researchers from Vall d´Hebron University Hospital Research Institute, Spain, initiated a phase II clinical study, following 15 people with CLE, for between 7 and 30 months, all of which had previously not responded to traditional therapy.

All but one of the people involved in the trial saw clinical improvement and most of these (86%) had complete response, reaching a CLASI score of 0. Three quarters of people who improved with lenalidomide relapsed within 2-8 weeks of the medication being stopped or reduced.

In this study side effects were minor. Only two people reported side effects  although for one person their gastrointestinal symptoms meant that they stopped taking lenalidomide after one week. For both people the side effects disappeared once they stopped taking the drug.

Ref : http://arthritis-research.com/content/14/6/R265/abstract

Saturday, December 1, 2012

Promising drug slows down advance of Parkinson's disease and improves symptoms

The research team, led by senior author Jay S. Schneider, Ph.D., Director of the Parkinson's Disease Research Unit and Professor in the Department of Pathology, Anatomy and Cell Biology and the Department of Neurology at Jefferson, found that administration of GM1 ganglioside, a substance naturally enriched in the brain that may be diminished in Parkinson's disease brains, acted as a "neuroprotective" and a "neurorestorative" agent to improve symptoms and over an extended period of time slow the progression of symptoms.


What's more, once the study participants went off the drug, their disease worsened. The study enrolled 77 subjects and followed them over a 120-week period and also followed 17 subjects who received current standard of care treatment for comparison.

"The drugs currently available for Parkinson's disease are designed to treat symptoms and to improve function, but at this time there is no drug that has been shown unequivocally to slow disease progression," said Dr. Schneider. "Our data suggest that GM1 ganglioside has the potential to have symptomatic and disease-modifying effects on Parkinson's disease. If this is substantiated in a larger clinical study, GM1 could provide significant benefit for Parkinson's disease patients."

Ref : http://www.jns-journal.com/article/S0022-510X%2812%2900581-3/abstract


Promising drug slows down advance of Parkinson's disease and improves symptoms

Friday, November 30, 2012

Diabetes drug rosiglitazone, improves memory, study suggests

In continuation of my update on rosiglitazone 

Working with genetically engineered mice designed to serve as models for Alzheimer's, University of Texas Medical Branch at Galveston researchers found that treatment with the anti-insulin-resistance drug rosiglitazone enhanced learning and memory as well as normalized insulin resistance. The scientists believe that the drug produced the response by reducing the negative influence of Alzheimer's on the behavior of a key brain-signaling molecule.

"Using this drug appears to restore the neuronal signaling required for proper cognitive function," said UTMB professor Larry Denner, the lead author of a paper describing this work now online in the Journal of Neuroscience. "It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer's patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer's."

Ref : http://www.utmb.edu/newsroom/article8071.aspx

Tuesday, November 27, 2012

New drug, regorafenib overcomes resistance in patients with rare sarcoma, study suggests

In continuation of my update on regorafenib

A new targeted drug demonstrated its ability to control metastatic gastrointestinal stromal tumor, an uncommon and life-threatening form of sarcoma, after the disease had become resistant to all existing therapies, report investigators at Dana-Farber Cancer Institute who led the worldwide clinical trial.

The oral drug regorafenib (see structure), which inhibits several cancer-promoting kinase enzymes, was able to control GIST for nearly four months longer than placebo in patients for whom Gleevec and Sutent were no longer effective, a result that was highly significant statistically.

"When added to best supportive care, regorafenib significantly improves disease control, as measured by progression-free survival time in patients with GIST after progression which represents failure of all other therapies," said George Demetri, MD, of Dana-Farber, principal investigator of this clinical trial.
Demonstrating the aggressive nature of this resistant disease, the study found that tumors objectively grew in less than a month, on average, in GIST patients who were initially randomized to receive a placebo. The study's "cross-over" design made it possible to treat those patients whose tumors grew, and 85 percent of the patients initially on placebo were able to receive regorafenib, which then controlled the disease in these patients as well.

Because of the study's cross-over design, Demetri said, it was not expected to prove that the patients initially randomized to receive regorafenib survived longer -- the researchers would have had to withhold the drug from the placebo patients to demonstrate that difference. "But there is no question that people are living longer" with regorafenib treatment, he said, based on the results of this trial.
An application to have regorafenib approved for use in resistant GIST is under an accelerated review by the Food and Drug Administration, Demetri said.