GABA injections prevent and reverse Type 1 diabetes in mice

A chemical produced in the pancreas that prevented and even reversed Type 1 diabetes in mice had the same effect on human beta cells transplanted into mice, new research has found. GABA, or gamma-aminobutryic acid, is an amino acid produced by the same beta cells that make and secrete insulin. 

Drs. Gerald Prud'homme and Qinghua Wang of the Keenan Research Centre for Biomedical Sciences of St. Michael's Hospital published a paper in 2011 showing for the first time that GABA injections not only prevented Type 1 diabetes in mice, but even reversed the disease.

A new paper published (Nov. 29) in the December issue of Diabetes shows GABA does the same thing in mice who have been injected with human pancreatic cells.

Type 1 diabetes, formerly known as juvenile diabetes, is characterized by the immune system's destruction of the beta cells in the pancreas. As a result, the body makes little or no insulin. The only conventional treatment for Type 1 diabetes is insulin injection, but insulin is not a cure as it does not prevent or reverse the loss of beta cells.

Drs. Prud'homme and Wang also found that GABA vastly improved the survival rate of pancreatic cells when they were being transplanted into mice. About 70 per cent of pancreatic cells die between the time the organ is harvested and transplanted. The researchers said their finding could lead to future research specifically related to pancreatic transplants.

GABA injections prevent and reverse Type 1 diabetes in mice

Avanir Pharmaceuticals Announces Preliminary Feedback from the FDA on AVP-825 for the Acute Treatment of Migraine

We know that, Sumatriptan is a synthetic drug belonging to the triptan class, used for the treatment of migraine headaches. Structurally, it is an analog of the naturally occurring neuro-active alkaloids dimethyltryptamine (DMT), bufotenine, and 5-methoxy-dimethyltryptamine, with an N-methyl sulfonamidomethyl- group at position C-5 on the indole ring

Now Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR) today announced that the U.S. Food and Drug Administration (FDA) has issued preliminary written feedback to its New Drug Application (NDA) for AVP-825. AVP-825 is a drug-device combination product consisting of low-dose sumatriptan powder, delivered intranasally utilizing a novel Breath Powered delivery technology. The FDA has raised questions regarding the human factor validation study data submitted as part of the NDA. Human factor testing focuses on the interactions between people and devices. The goal of human factor testing is to evaluate use-related risks and confirm that users can use the device safely and effectively. Although the NDA review is ongoing, Avanir has concluded, at this time, that approval of AVP-825 may be unlikely by the PDUFA date of November, 26, 2014

Avanir Pharmaceuticals Announces Preliminary Feedback from the FDA on AVP-825 for the Acute Treatment of Migraine

Experimental anti-cancer drugs PF-04691502 and PD-0325901 excel against colorectal cancer models

Genes make proteins and proteins tell your body's cells what to do: one talks to the next, which talks to the next, and to the next. Like a game of telephone, researchers call these  "signaling pathways". Abnormalities in these signaling pathways can cause the growth and survival of cancer cells. Commonly, mutations or rearrangements of genes in the MAPK  signaling pathway create cancer's fast growth, and alterations in the PI3K signaling pathway allow cancer cells to survive into virtual immortality.

Of course, researchers have extensively targeted these two signaling pathways, designing drugs that turn on or off genes in these pathways, thus interrupting the transmission of cancer-causing signals. Unfortunately, these pathways have proven difficult to drug and also it has been difficult to show the effectiveness of drugs that successfully interrupt the transmission of signals along these pathways.

A study by the University of Colorado Cancer Center published in the journal PLoS ONE and concurrent phase I clinical trial is examining a new strategy: targeting both these important cancer-causing pathways simultaneously.

"Well, these two pathways are mutated frequently in cancer. Why not hit both of them? It was as simplistic as that," says Todd Pitts, MS, research instructor in the Program for the Evaluation of Targeted Therapies, and the study's first author.

The study used colorectal cancer tumors grown on mice from samples of patient tumors, called "patient-derived xenograft" models. To these tumors, Pitts and colleagues added the experimental anti-cancer drugs PF-04691502 (left structure) and PD-0325901 (right structure), the first of which mutes a link in the PI3K signaling pathway and the second of which mutes a link in the MAPK signaling pathway. In this case, the combination was greater than the sum of the parts - alone, PF-04691502 and PD-0325901 modestly inhibit the growth and survival of colorectal cancer in these models; after 30-day exposure to the combination, colorectal cancer cells were killed much more effectively than by either drug alone, and even more effectively than if you added together the cells killed by each drug alone.

Experimental anti-cancer drugs PF-04691502 and PD-0325901 excel against colorectal cancer models

Scientists devise powerful algorithm to improve effectiveness of research technology harnessing RNAi

In continuation of my update on RNAi

Scientists at Cold Spring Harbor Laboratory (CSHL) have devised a powerful algorithm that improves the effectiveness of an important research technology harnessing RNA interference, or RNAi.

Discovered in the late 1990s, RNAi is a naturally occurring biological mechanism in which short RNA molecules bind to and "interfere" with messages sent by genes that contain instructions for protein production. Such interference can prevent a gene from being expressed. In addition to helping regulate gene expression, the RNAi pathway in many species, including humans, acts to defend the genome from parasitic viruses and transposons.

Harnessed by scientists since the mid-2000s, RNAi has provided a way to artificially "knock down" the expression of specific genes. By preventing a gene or genes from being activated in a model organism such as a mouse, for instance, much can be learned by inference about gene function. RNAi-based technology also has been extremely useful as tool in drug discovery.

Scientists devise powerful algorithm to improve effectiveness of research technology harnessing RNAi

Researchers demonstrate efficacy of Bozepinib drug against cancerogenic stem cells

An Andalusian team of researchers led by the University of Granada has demonstrated the efficacy of a new drug against cancerogenic stem cells, which cause the onset and development of cancer, of relapse after chemotherapy and metastasis. This drug, called Bozepinib, has proved to be effective in tests with mice. The results have been published in the prestigious journal Oncotarget.

Cancerogenic stem cells appear in small quantities in tumours, and one of their important features is that they contribute to the formation of metastasis in different places within the original tumour. Cancerogenic stem cells remain dormant under normal conditions (i.e. they do not divide). Conventional chemotherapy and radiotherapy act upon those cancer cells which are clearly differentiated—i.e. which are undergoing processes of division—but they cannot destroy these dormant cancerogenic stem cells. Actually, after a positive initial response to treatment, many cancer patients suffer a relapse because these cancerogenic stem cells have not been destroyed.

Researchers demonstrate efficacy of Bozepinib drug against cancerogenic stem cells

Experimental drug works best when patients' immune cells surrounding tumors express PD-L1

A promising experimental immunotherapy drug works best in patients whose immune defenses initially rally to attack the cancer but then are stymied by a molecular brake that shuts down the response, according to a new study led by researchers at Dana-Farber Cancer Institute and the Yale University School of Medicine.

The antibody drug, known as MPDL3280A, inhibits the brake protein, PD-L1, reviving the response by immune killer T cells, which target and destroy the cancer cells. In recent clinical trials, the PD-L1 checkpoint blocker caused impressive shrinkage of kidney, melanoma, and lung tumors. But, as with other immunotherapy drugs, many patients saw no benefit.

Researchers report in the November 27 edition of Nature that the antibody was most effective when the patients' immune cells surrounding tumors expressed PD-L1 - a sign that a pre-existing immune response had been shut down by PD-L1. There was less tumor shrinkage in patients who never developed an immune response to the cancer - and, as a result, had less PD-L1 in the cancer and surrounding tissues.

"I think this is a launching point to use these findings as a predictive biomarker," said F. Stephen Hodi, MD, of Dana-Farber, senior author of the report. Hodi directs the Center for Immuno-Oncology and the Melanoma Treatment Center at Dana-Farber. First author is Roy Herbst, MD, PhD, chief of Medical Oncology at the Yale Comprehensive Cancer Center.

The scientists studied tumor tissue samples from 175 patients treated in clinical trials with MPDL3280A for advanced non-small cell lung cancer, melanoma, kidney cancer, and other cancers. On average, 18 percent of the patients had complete or partial shrinkage of their tumors, with higher or lower rates in different cancer types. Overall, the treatment was well-tolerated, with few severe side-effects, the report said.

Ref : http://meetinglibrary.asco.org/content/83740?media=vm

Experimental drug works best when patients' immune cells surrounding tumors express PD-L1

Destroy Cancer Naturally in 40 Days

We know that, Tripterygium wilfordii, or léi gōng téng (Mandarin) (Chinese:雷公藤, Japanese: raikōtō), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine for treatment of fever, chills, edema and carbuncle.

Tripterygium wilfordii recently has been investigated as a treatment for a variety of disorders including rheumatoid arthritis,cancer, chronic hepatitis, chronic nephritis, ankylosing pondylitis, polycystic kidney disease as well as several skin disorders. It is also under investigation for its apparent antifertility effects, which it is speculated, may provide a basis for a Male oral contraceptive. Now University of Minnesota Masonic Cancer Center, researchers have reported that, ancient Chinese medicine is bringing renewed hope to cancer sufferers, all thanks to an herb called thunder god vine. For starters, this herb may make it possible to purge tumors from the body without resorting to chemotherapy or other intense interventions.

On top of that, early evidence shows thunder god vine could be particularly effective in hindering the growth of pancreatic, colorectal, and ovarian cancers, among others.

Destroy Cancer Naturally in 40 Days | Cancer Defeated

Visualizing DNA double-strand break process for the first time

Scientists from the Spanish National Cancer Research Centre (CNIO), led by Guillermo Montoya, have developed a method for producing biological crystals that has allowed scientists to observe  for the first time-- DNA double chain breaks. They have also developed a computer simulation that makes this process, which lasts in the order of millionths of a second, visible to the human eye. The study is published today by the journalNature Structural & Molecular Biology.

"We knew that enzymes, or proteins, endonucleases, are responsible for these double strand breaks, but we didn't know exactly how it worked until now," said Montoya. "In our study, we describe in detail the dynamics of this basic biological reaction mediated by the enzyme I-Dmol. Our observations can be extrapolated to many other families of endonucleases that behave identically."

DNA breaks occur in several natural processes that are vital for life: mutagenesis, synthesis, recombination and repair. In the molecular biology field, they can also be generated synthetically. Once the exact mechanism that produces these breaks has been uncovered, this knowledge can be used in multiple biotechnological applications: from the correction of mutations to treat rare and genetic diseases, to the development of genetically modified organisms.

Slow-motion reaction

Enzymes are highly specialised dynamic systems. Their nicking function could be compared, said Montoya, to a specially designed fabric-cutting machine that "it would only make a cut when a piece of clothing with a specific combination of colours passed under the blade."

In this case, researchers concentrated on observing the conformational changes that occurred in the I-Dmol active site; the area that contains the amino acids that act as a blade and produces DNA breaks.

By altering the temperature and pH balance, the CNIO team has managed to delay a chemical reaction that typically occurs in microseconds by up to ten days. Under those conditions, they have created a slow-motion film of the whole process.

"By introducing a magnesium cation we were able to trigger the enzyme reaction and subsequently to produce biological crystals and freeze them at -200ºC," said Montoya. "In that way, we were able to collect up to 185 crystal structures that represent all of the conformational changes taking place at each step of the reaction."

Finally, using computational analysis, the researchers illustrated the seven intermediate stages of the DNA chain separation process. "It is very exciting, because the elucidation of this mechanism will give us the information we need to redesign these enzymes and provide precise molecular scissors, which are essential tools for modifying the genome," he concluded.

Visualizing DNA double-strand break process for the first time  

New treatment for marfan syndrome shows promise

In continuation of my update on Losartan

The results are being presented Nov. 18 at the American Heart Association's annual meeting in Chicago and will appear online the same day in The New England Journal of Medicine.

"For years, standard medical therapy for Marfan syndrome consisted of giving patients beta blockers, which lower heart rate and blood pressure, reducing stress on the wall of the aorta," said study co-author Alan C. Braverman, MD, a cardiologist at Washington University School of Medicine in St. Louis. "This new study suggests that we have a second option for patients that appears to be as effective as standard treatment."

The second option is Losartan (see above structure) , an angiotensin receptor blocker. Past research in mice and smaller clinical trials suggested that this class of drugs might actually be superior to beta blocker treatment for Marfan syndrome. Angiotensin receptor blockers commonly are prescribed to treat high blood pressure.

People with Marfan syndrome have weak connective tissues and tend to develop unusually long arms, legs and fingers. In addition to heart problems, patients often develop problems with the eyes, lungs, bones and joints. Patients with the condition are at high risk of sudden death from a tear in the aorta, also called an aortic dissection.

Though there is no cure for Marfan syndrome, treatment with beta blockers and preventive surgery to replace the section of the aorta adjacent to the heart has increased lifespan to near normal. But physicians have continued to look for more effective therapies, especially since some patients on beta blockers experience side effects such as tiredness and nausea.

So investigators in the Pediatric Heart Network of the National Institutes of Health (NIH), including Braverman and senior author Ronald V. Lacro, MD, a cardiologist at Harvard Medical School and Boston Children's Hospital, conducted a clinical trial comparing the beta blocker Atenolol with Losartan.

The study included 608 patients with Marfan syndrome at 21 medical centers nationwide. Patients were ages 6 months to 25 years and had enlarged aortas. Half of these participants were randomly given Losartan, the investigational treatment, and the other half received Atenolol, the standard therapy, but in higher doses than physicians typically prescribe to see if this would increase the beta blocker's effectiveness.

After following participants for three years, the investigators reported no differences between the two groups in the growth rate of the aorta. They further observed similar rates of tears in the aorta, similar numbers of surgeries required to repair these tears and no difference in the number of deaths between the two groups.

New treatment for marfan syndrome shows promise  

New treatment for marfan syndrome shows promise

The results are being presented Nov. 18 at the American Heart Association's annual meeting in Chicago and will appear online the same day in The New England Journal of Medicine.

"For years, standard medical therapy for Marfan syndrome consisted of giving patients beta blockers, which lower heart rate and blood pressure, reducing stress on the wall of the aorta," said study co-author Alan C. Braverman, MD, a cardiologist at Washington University School of Medicine in St. Louis. "This new study suggests that we have a second option for patients that appears to be as effective as standard treatment."

The second option is Losartan, an angiotensin receptor blocker. Past research in mice and smaller clinical trials suggested that this class of drugs might actually be superior to beta blocker treatment for Marfan syndrome. Angiotensin receptor blockers commonly are prescribed to treat high blood pressure.

People with Marfan syndrome have weak connective tissues and tend to develop unusually long arms, legs and fingers. In addition to heart problems, patients often develop problems with the eyes, lungs, bones and joints. Patients with the condition are at high risk of sudden death from a tear in the aorta, also called an aortic dissection.

Though there is no cure for Marfan syndrome, treatment with beta blockers and preventive surgery to replace the section of the aorta adjacent to the heart has increased lifespan to near normal. But physicians have continued to look for more effective therapies, especially since some patients on beta blockers experience side effects such as tiredness and nausea.

So investigators in the Pediatric Heart Network of the National Institutes of Health (NIH), including Braverman and senior author Ronald V. Lacro, MD, a cardiologist at Harvard Medical School and Boston Children's Hospital, conducted a clinical trial comparing the beta blocker Atenolol with Losartan.

The study included 608 patients with Marfan syndrome at 21 medical centers nationwide. Patients were ages 6 months to 25 years and had enlarged aortas. Half of these participants were randomly given Losartan, the investigational treatment, and the other half received Atenolol, the standard therapy, but in higher doses than physicians typically prescribe to see if this would increase the beta blocker's effectiveness.

After following participants for three years, the investigators reported no differences between the two groups in the growth rate of the aorta. They further observed similar rates of tears in the aorta, similar numbers of surgeries required to repair these tears and no difference in the number of deaths between the two groups.

New treatment for marfan syndrome shows promise