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

New antidepressant acts very rapidly and is long lasting

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.

Severe morning sickness patients get relief from anti-seizure drug

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

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

Linagliptin may reduce brain damage following stroke in type 2 diabetic patients

In continuation of my update on Linagliptin...
Linagliptin may reduce brain damage following stroke in type 2 diabetic patients

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

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

Diabetes drug improves memory, study suggests

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.

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

Potential role of green tea catechins in various disease therapies: Progress and promise Mak 2012 Clinical and Experimental Pharmacology and Physiology Wiley Online Library

Potential role of green tea catechins in various disease therapies: Progress and promise Mak 2012 Clinical and Experimental Pharmacology and Physiology Wiley Online Library

Positive results from Genentech Avastin plus temozolomide Phase III study on glioblastoma

Positive results from Genentech Avastin plus temozolomide Phase III study on glioblastoma: Genentech, a member of the Roche Group, today announced results from the positive Phase III AVAglio study. The study showed Avastin (bevacizumab) in combination with radiation and temozolomide (see structure below) chemotherapy reduced the risk of cancer worsening or death (progression-free survival; PFS) by 36 percent compared to radiation and temozolomide chemotherapy plus placebo>17th Annual Meeting of the Society for Neuro-Oncology in Washington, D.C.

Ref : http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=14247

CLR01 effectively inhibits synaptotoxicity in mice with Alzheimer's

We know that, aggregation of α-synuclein (α-syn) is implicated as being causative in the pathogenesis of Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. Despite several therapies that improve symptoms in these disorders, none slow disease progression. Recently, a novel“molecular tweezer”(MT) termed CLR01 (see structure) has been described as a potent inhibitor of assembly and toxicity of multiple amyloidogenic proteins....

"This is the first demonstration that molecular tweezers work in a mammalian animal model," said Gal Bitan, an associate professor of neurology at UCLA and the senior author of the study. "Importantly, no signs of toxicity were observed in the treated mice. The efficacy and toxicity results support the mechanism of this molecular tweezer and suggest these are promising compounds for developing disease-modifying therapies for Alzheimer's disease, Parkinson's and other disorders."

Molecular tweezers are complex molecular compounds capable of binding to other proteins. Shaped like the letter "C," these compounds wrap around chains of lysine, a basic amino acid that is a constituent of most proteins. Bitan and his colleagues, including Aida Attar, first author of the study and a graduate student in Bitan's lab, have been working with a particular molecular tweezer called CLR01.

In collaboration with scientists at the Università Cattolica in Rome, the researchers, working first in cell cultures, found that CLR01 effectively inhibited a process known as synaptotoxicity, in which clumps of toxic amyloid damage or destroy a neuron's synapses.

Even though synapses in transgenic mice with Alzheimer's may shut down and the mice may lose their memory, upon treatment, they form new synapses and regain their learning and memory abilities.