Researchers identify compounds that could lead to discovery of new drugs for African sleeping sickness

In early drug discovery, you need a starting point, says North­eastern Uni­ver­sity asso­ciate pro­fessor of chem­istry and chemical biology Michael Pollastri.

In a new research paper published Thursday in the journal PLOS Neglected Tropical Diseases, Pollastri and his colleagues present hun­dreds of such starting points for poten­tially treating African sleeping sick­ness, a deadly disease that claims thousands of lives annually.

Pol­lastri, who runs Northeastern's Lab­o­ra­tory for Neglected Dis­ease Drug Dis­covery, and co- collaborators at the Spanish National Research Council for Scientific Research worked with global health­care com­pany GlaxoSmithKline to screen and test more than 42,000 chem­ical com­pounds against the par­a­sites that cause African sleeping sickness. In their paper, they report iden­ti­fying nearly 800 com­pounds that rep­re­sent good options for early drug discovery.

"Having this many good starting points for discovery of new drugs for sleeping sick­ness is a big deal and could ultimately lead to a cure," Pol­lastri said.

Pol­lastri also high­lighted another exciting component to this project. Previously, he created a data- sharing portal where sci­en­tists and researchers can access and con­tribute to each other's work on neglected tropical diseases. This new research on African sleeping sickness will be the first data to be deposited on the portal, which was sup­ported by a crowd­funding campaign.

"This is a venue where other people, particularly medical chemists from around the world, can con­tribute to the project in one way or the other," Pollastri said.

Researchers identify compounds that could lead to discovery of new drugs for African sleeping sickness

MIT researchers develop new way to model effects of cancer-causing genetic mutations

Sequencing the genomes of tumor cells has revealed thousands of genetic mutations linked with cancer. However, sifting through this deluge of information to figure out which of these mutations actually drive cancer growth has proven to be a tedious, time-consuming process.

MIT researchers have now developed a new way to model the effects of these genetic mutations in mice. Their approach, based on the genome-editing technique known as CRISPR, is much faster than existing strategies, which require genetically engineering mice that carry the cancerous mutations.

"It's a very rapid and very adaptable approach to make models," says Thales Papagiannakopoulos, a postdoc at MIT's Koch Institute for Integrative Cancer Research and one of the lead authors of the paper, which appears in the Oct. 22 online edition ofNature. "With a lot of these mutations, we have no idea what their role is in tumor progression. If we can actually understand the biology, we can then go in and try targeted therapeutic approaches."

Led by Papagiannakopoulos, graduate student Francisco Sanchez-Rivera, the paper's other lead author, and Koch Institute director Tyler Jacks, the paper's senior author, the team used CRISPR to accurately reproduce the effects of two well-known lung cancer genes. They also modeled a gene called APC, whose role in lung cancer was not previously known.

This approach could be used to study nearly any gene in many different types of cancer, the researchers say. "There has to be a functional way of assessing the role of these cancer-gene candidates as they appear in sequencing studies," Sanchez-Rivera says. "The system we developed fills that gap immediately because you can do it very rapidly and very precisely."

Ref  http://newsoffice.mit.edu/2014/fast-modeling-cancer-mutations-1022

MIT researchers develop new way to model effects of cancer-causing genetic mutations

Scientists develop new drug as alternative to antibiotics

In a breakthrough, scientists have developed the first effective alternative to antibiotics that may aid the fight against drug-resistant infections. 

In a small patient trial, the drug was shown to be effective at eradicating the superbug Methicillin-resistant Staphylococcus aureus (MRSA). 

Researchers said it is unlikely that the infection could develop resistance against the new treatment, which is already available as a cream for skin infections. 

They hope to develop a pill or an injectable version of the drug within five years. 

The treatment marks "a new era in the fight against antibiotic-resistant bacteria," according to Mark Offerhaus, chief executive of the biotechnology company Micreos, which is behind the advance. 

The treatment attacks infections in an entirely different way from conventional drugs and, unlike them, exclusively targets the Staphylococcus bacteria responsible for MRSA, and leaves other microbes unaffected. 

The approach is inspired by naturally occurring viruses that attack bacteria using enzymes called endolysins. It uses a 'designer' endolysin, Staphefekt, which the scientists engineered to latch on to the surface of bacteria cells and tear them apart, 'The Times' reported. 

"Endolysins exist in nature, but we've made a modified version that combines the bit that is best at binding to the bacteria with another bit that is best at killing it," said Bjorn Herpers, a clinical microbiologist, who tested the drug at the Public Health Laboratory in Kennemerland, the Netherlands. 

Conventional antibiotics need to reach the inside of the cell to work, and part of the reason they are becoming less effective is that certain strains of bacteria, such as MRSA, have evolved impenetrable membranes. 

Scientists develop new drug as alternative to antibiotics  

Analgesics, anti-inflammatory drugs have beneficial effect on treatment of depression

Analgesics and anti-inflammatory drugs used against muscle pain and arthritis may have a beneficial effect on depression symptoms....

Ordinary over the counter painkillers and anti-inflammatory drugs purchased from pharmacies may also be effective in the treatment of people suffering of depression.

This is shown by the largest ever meta-analysis that has just been published by a research group from Aarhus University in the American scientific journal JAMA Psychiatry. The meta-analysis is based on 14 international studies with a total 6,262 patients who either suffered from depression or had individual symptoms of depression.

Up to 15 per cent of the Danish population can expect to suffer from depression at some point in their lives. The World Health Organisation (WHO) estimates that depression is one of the top five reasons for loss of quality of life and also life years. Thus, it is a very serious condition, one where researchers all over the world are constantly trying to find more effective treatments.

In recent years research has demonstrated a correlation between depression and physical illnesses, such as painful conditions or infections in the individual patient.

"The meta-analysis supports this correlation and also demonstrates that anti-inflammatory medication in combination with antidepressants can have an effect on the treatment of depression. When combined they give an important result which, in the long term, strengthens the possibility of being able to provide the individual patient with more personalized treatment options," says MD-student Ole Köhler, who is first author of the scientific article and a member of the research group from Aarhus University.

Analgesics, anti-inflammatory drugs have beneficial effect on treatment of depression

Walnuts may help prevent Alzheimer's disease, study finds

Animal study reveals potential brain-health benefits of a walnut-enriched diet. A new animal study published in the Journal of Alzheimer's Disease indicates that a diet including walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer's disease.

Research led by Abha Chauhan, PhD, head of the Developmental Neuroscience Laboratory at the New York State Institute for Basic Research in Developmental Disabilities (IBR), found significant improvement in learning skills, memory, reducing anxiety, and motor development in mice fed a walnut-enriched diet.

The researchers suggest that the high antioxidant content of walnuts (3.7 mmol/ounce) may have been a contributing factor in protecting the mouse brain from the degeneration typically seen in Alzheimer's disease. Oxidative stress and inflammation are prominent features in this disease, which affects more than five million Americans.

More : http://www.j-alz.com/node/396

Walnuts may help prevent Alzheimer's disease, study finds

Afatinib active against NSCLC nervous system metastases

Incontinuation of my update on Afatinib

Afatinib active against NSCLC nervous system metastases

Nanoparticle-based invention moves new drugs closer to clinical testing

Penn State College of Medicine researchers have developed a nanoparticle to deliver a melanoma-fighting drug directly to the cancer.

Delivering cancer drugs directly to tumors is difficult. Scientists are working on new approaches to overcome the natural limitations of drugs, including loading them into nanoparticles.

"The drug is packaged into a lipid ball significantly smaller than the width of a hair to make it soluble in the blood stream and prevent negative side effects. The drug-containing nanoparticle ball then travels in the bloodstream to the tumor, where it accumulates and the drug is released in the tumor to kill the cancer cells," said Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery and director of the Penn State Hershey Melanoma Center.

In previous research, Robertson discovered the cancer-fighting characteristics of leelamine, a substance derived from pine bark. But leelamine cannot be given by mouth because of poor uptake in the gastrointestinal tract or be injected intravenously because it causes damage to red blood cells.

To address this issue, Robertson and his team developed a new nanoliposome that loads leelamine, called Nanolipolee-007. Nanolipolee-007 can be injected intravenously without causing damage to red blood cells. It then accumulates in tumors because of its small size where it releases the drug to kill the cancer cells.

Leelamine is the first of a new unique class of drugs that inhibits cholesterol movement around a cancer cell to shut down signals needed for cancer cell survival. As a result, protein pathways like the PI3K, MAPK and STAT3 that are highly active and help cancer cells multiply and spread, are turned off and the cancer cells die. Since normal cells are not addicted to the high levels of activity of these pathways that occur in cancer cells, the drug has a minor effect on them.

"This nanoparticle moves leelamine one step closer to the clinic," Robertson said. "We now have a drug that has the potential to be given to humans that could not be done before."

The researchers showed the results of Nanolipolee-007 on cells growing in culture dishes and in tumors growing in mice following intravenous injection. Leelamine inhibited tumor development in mice with no detectable side effects.

Nanoparticle-based invention moves new drugs closer to clinical testing  

VAL-083 drug compound shows promise against non-small cell lung cancer

We know that, VAL-083 is a bi-functional alkylating agent; inhibit U251 and SF188 cell growth in monolayer better than TMZ and caused apoptosis.

DelMar Pharmaceuticals, Inc., (OTCQB: DMPI), a clinical-stage oncology company, today announced the presentation of promising new data supporting the activity of its lead drug compound, VAL-083, in the treatment of non-small cell lung cancer (NSCLC) at the AACR's New Horizons in Cancer Research: Harnessing Breakthroughs – Targeting Cures. The conference takes place October 9th to 12th in Pudong, Shanghai.

"The data presented today showed that VAL-083 is superior to cisplatin in both tumor models that are sensitive and resistant to tyrosine kinase inhibitors and has synergistic effect in combination with cisplatin," said Jeffrey Bacha, president and CEO of DelMar Pharmaceuticals. "This data suggests important clinical and market potential of VAL-083 in non-small cell lung cancer."

DelMar's lead clinical compound, VAL-083 (dianhydrogalactitol) is a first-in-class alkylating agent with a novel cytotoxic mechanism distinct from other alkylating agents used in the treatment of cancer.

In historical studies sponsored by the National Cancer Institute in the United States, VAL-083 exhibited clinical activity against a range of tumor types including CNS tumors, solid tumors and hematologic malignancies. VAL-083 is approved in China for the treatment ofchronic myelogenous leukemia (CML) and lung cancer (Approval No. Guoyao Zhunzi H45021133; manufactured by Guangxi Wuzhou Pharmaceutical (Group) Co. Ltd.)

NSCLC is usually treated with either tyrosine kinase inhibitors (TKIs) (e.g. gefitinib) or platinum-based regimens (e.g. cisplatin). TKIs have resulted in vastly improved outcomes for patients with EGFR mutations; however, TKI resistance has emerged as a significant unmet medical need, and long-term prognosis with platinum-based therapies is poor. Compared to other countries, Asian patients with NSCLC have a higher incidence of EGFR mutations (up to 60 percent; compared to 10-20 percent in Western populations) and are more susceptible to TKI resistance.

Additionally, NSCLC patients have a high incidence of brain metastases, which is associated with a poor prognosis. The median overall survival time for patients with stage IV NSCLC is four months, while one-year and five-year survival is less than 16 percent and 2 percent, respectively. VAL-083 can cross the blood-brain barrier and is currently being evaluated in the United States in a Phase 1/2 clinical trial to treat the most common form of brain cancer, glioblastoma multiforme (GBM).

 

VAL-083 drug compound shows promise against non-small cell lung cancer

Synthetic oil triheptanoin improves Rett syndrome, longevity

We know that, Triheptanoin is a triglyceride that is composed of three seven-carbon fatty acids. These odd-carbon fatty acids are able to provide anaplerotic substrates for the TCA cycle. Triheptanoin is used clinically in humans to treat inherited metabolic diseases, such aspyruvate carboxylase deficiency and carnitine palmitoyltransferase II deficiency. It also appears to increase the efficacy of the ketogenic diet as a treatment for epilepsy.

Now the research team used mice lacking the MeCP2 protein, which left them with severe Rett syndrome. In examining those mice, what stood out, according to Gabriele Ronnett, M.D., Ph.D., who led the research project at the Johns Hopkins University School of Medicine, was that they weighed the same as healthy mice but had large fat deposits accompanied by lower amounts of nonfat tissue, such as muscle. This suggested that calories were not being used to support normal tissue function but instead were being stored as fat.

This possibility led Ronnett and her research team to consider the role of mitochondria, which transform the building blocks of nutrients into a high-energy molecule, ATP. This molecule drives processes such as the building of muscle and the growth of nerve cells. Mitochondria use a series of biochemical reactions, collectively called the TCA cycle, to make this transformation possible. According to Susan Aja, Ph.D., a research associate and lead member of the research team, "If the components of the TCA cycle are low, nutrient building blocks are not processed well to create ATP. They are instead stored as fat."

Synthetic oil triheptanoin improves Rett syndrome, longevity

Akynzeo Approved for Side Effects of Chemotherapy

The combination drug Akynzeo [netupitant (left) and palonosetron (right)] has been approved by the U.S. Food and Drug Administration to treat nausea and vomiting among people undergoing chemotherapy, the agency said Friday in a news release.

Akynzeo contains a new anti-nausea drug, netupitant, and palonosetron, which was approved to treat nausea and vomiting in 2008.

The combination drug's effectiveness was evaluated in two clinical studies involving 1,720 people. The trials established that Akynzeo was more effective in preventing nausea and vomiting than palonosetron taken alone, the FDA said.

The most frequent side effects of the combination drug included headache, weakness, fatigue, indigestion and constipation.

Akynzeo is marketed and distributed by Eisai Inc. of Woodcliff Lake, N.J., under license from Switzerland-based Helsinn Healthcare.

Akynzeo Approved for Side Effects of Chemotherapy