From the 7 March 2016 University of Toronto news release
Professor Milica Radisic and her team have created a new platform for growing realistic human heart and liver tissue outside the body. The technique could help drug companies discover and prevent negative side effects. (Photo: Caz Zyvatkauskas)
Researchers at U of T Engineering have developed a new way of growing realistic human tissues outside the body. Their “person-on-a-chip” technology, called AngioChip, is a powerful platform for discovering and testing new drugs, and could eventually be used to repair or replace damaged organs.
Professor Milica Radisic (IBBME, ChemE), graduate student Boyang Zhang and their collaborators are among those research groups around the world racing to find ways to grow human tissues in the lab, under conditions that mimic a real person’s body. They have developed unique methods for manufacturing small, intricate scaffolds for individual cells to grow on. These artificial environments produce cells and tissues that resemble the real thing more closely than those grown lying flat in a petri dish.
Left to right: Team members Miles Montgomery, Professor Milica Radisic, Boyang Zhang and Yimu Zhao (Photo: Geoff George)
The team’s recent creations have included BiowireTM — an innovative method of growing heart cells around a silk suture — as well as a scaffold for heart cells that snaps together like sheets of Velcro™. But AngioChip takes tissue engineering to a whole new level. “It’s a fully three-dimensional structure complete with internal blood vessels,” says Radisic. “It behaves just like vasculature, and around it there is a lattice for other cells to attach and grow.” The work — which is published todayin the journal Nature Materials — was produced collaboratively with researchers from across U of T, including Professor Michael Sefton (ChemE, IBBME), Professor Aaron Wheeler (Chemistry, IBBME) and their research teams, as well as researchers from Toronto General Hospital and University Health Network.
Zhang built the scaffold out of POMaC, a polymer that is both biodegradable and biocompatible. The scaffold is built out of a series of thin layers, stamped with a pattern of channels that are each about 50 to 100 micrometres wide. The layers, which resemble the computer microchips, are then stacked into a 3D structure of synthetic blood vessels. As each layer is added, UV light is used to cross-link the polymer and bond it to the layer below.
These tiny polymer scaffolds contain channels that are about 100 micrometres wide, about the same diameter as a human hair. When seeded with cells, the channels act as artificial blood vessels. By mimicking tissues in the human heart and other organs, these scaffolds provide a new way to test drugs for potentially dangerous side effects. (Image: Tyler Irving/Boyang Zhang/Kevin Soobrian)
When the structure is finished, it is bathed in a liquid containing living cells. The cells quickly attach to the inside and outside of the channels and begin growing just as they would in the human body.
Healing plants inspire new compounds for psychiatric drugs
From the 11 May 2015 Northwestern University news release
Scientists look to healers in Nigeria to develop better therapies for mental disorders
May 11, 2015 | by Erin Spain
EVANSTON, Ill. — Treatments used by traditional healers in Nigeria have inspired scientists at Northwestern University to synthesize four new chemical compounds that could one day lead to better therapies for people with psychiatric disorders.
In a paper published online in the journal Angewandte Chemie International Edition, the scientists detail how they created these natural compounds by completing the first total syntheses of two indole alkaloids — alstonine and serpentine. These alkaloids, found in various plant species used by healers in Nigeria to treat people with conditions such as schizophrenia and bipolar disorder, have antipsychotic properties that have potential to improve mental disorder treatments.
The current drugs used for schizophrenia effectively treat delusions and hallucinations but are only partially effective for cognitive impairment. Early experimental research of these new compounds in animal models shows promise in improving cognitive impairment, the Northwestern scientists said.
Traditional healers boil these special plants and produce an extract that they administer to people with symptoms of mental illness. However, this extract isn’t pure, and it contains other compounds and materials that may not be beneficial to people with mental disorders.
“Nature did not intend this plant to produce an antipsychotic drug on its own,” Meltzer said.
The collaborative work to create the compounds took place in the Center for Molecular Innovation and Drug Discovery (CMIDD) at Northwestern, using high-level purification resources and state-of-the-art research instrumentation and equipment. Scheidt is the director of CMIDD.
Through an efficient and stereo-selective synthesis, Scheidt and his team created four separate but related natural products. Now a template exists to continue making these compounds as needed for future studies and ultimately for use in clinical drug trials.
“We can make multi-gram quantities of any of the compounds we want,” Scheidt said. “We built the assembly line and are now uniquely positioned to explore their potential.”
Meltzer is already using these compounds in animal studies in his lab to better understand how they affect brain biology and chemistry in the schizophrenia disease model. Early results from his lab show that the compounds may increase the ability of other antipsychotic drugs to improve cognitive impairment.
Other study authors are Dr. Ashkaan Younai and Bi-Shun Zeng of Northwestern University. This study was supported the Chemistry of Life Processes Institute at Northwestern in the form of an Innovators Grant and the Weisman Family Foundation.
– See more at: http://www.northwestern.edu/newscenter/stories/2015/05/healing-plants-inspire-new-compounds-for-psychiatric-drugs.html#sthash.pHX8AWsh.dpuf
– See more at: http://www.northwestern.edu/newscenter/stories/2015/05/healing-plants-inspire-new-compounds-for-psychiatric-drugs.html#sthash.pHX8AWsh.dpuf
From the 29 March 2015 Sandia news release
LIVERMORE, Calif.—Technologies developed in Sandia National Laboratories’biosciences program could soon find their way into doctors’ offices — devices like wearable microneedles that continuously analyze electrolyte levels and a lab-on-a-disk that can test a drop of blood for 64 different diseases in minutes.
At a recent seminar for potential investors and licensees, part of the Sandia Technology Showcase series, Sandia bioscientists presented eight ready-to-license technologies in three key areas: medical diagnostics, biosurveillance and therapeutics and drug discovery.
From the 20 January 2015 BBC article
US scientists are asking the public to join them in their quest to mine the Earth’s soil for compounds that could be turned into vital new drugs.
Spurred on by the recent discovery of a potential new antibiotic in soil, the Rockefeller University team want to check dirt from every country in the world.
They have already begun analysing samples from beaches, forests and deserts across five continents.
But they need help getting samples.
Which is where we all come in.
On their Drugs From Dirt website, they say: “The world is a big place and we can’t get get to all of the various corners of it.
“We would like some assistance in sampling soil from around the world. If this sounds interesting to you – sign up.”
They want to hear from people from all countries and are particularly keen to receive samples from unique, unexplored environments such as caves, islands, and hot springs.
Such places, they say, could house the holy grail – compounds produced by soil bacteria that are entirely new to science.
Researcher Dr Sean Brady told the BBC: “We are not after hundreds of thousands of samples. What we really want is a couple of thousand from some really unique places that could contain some really interesting stuff. So it’s not really your garden soil we are after, although that will have plenty of bacteria in it too.”
He said they would also be interested to hear from schools and colleges that might want to get involved in the project.
From the 185 samples they have tested so far there are some promising results, the researchers say in the journal eLife.
Biosynthetic dark matter
Dr Brady and colleagues have found compounds that might yield better derivatives of existing drugs.
In a hot spring sample from New Mexico, they found compounds similar to those that produce epoxamicin – a natural molecule used as the starting point for a number of cancer drugs.
In samples from Brazil, they found genes that might offer up new versions of another important cancer drug called bleomycin.
And in soils from the American southwest, they hope to find compounds similar to the drug rifamycin that could help with treatment-resistant tuberculosis.
From the January 2014 news item at Edinburg University
New types of drug intended for use in place of antibiotics have been given a cautious welcome by scientists.
University researchers have been probing the long-term effectiveness of drugs currently being developed by the pharmaceutical industry.
These work by limiting the symptoms caused by a bug or virus in the body, rather than killing it outright.
These treatments are designed to avoid the problem of infections becoming resistant to treatment, which has become widespread with antibiotics.
This approach is intended to enable the patient to tolerate disease, and buy the immune system valuable time to get rid of the infection naturally.
Researchers at the Universities of Edinburgh and Liverpool created a mathematical model to look at how at how drugs that limit the damage caused by disease could affect how infections spread and evolve.
They found that for certain infections, where the symptoms are not linked to the spread of disease, these drugs may prevent disease from evolving too quickly.
They will be useful over longer periods of time.
However, scientists caution that people given damage limitation treatments may appear healthy, but carry high levels of infection and so may be more likely to pass on disease.
In addition, people with lesser symptoms could remain undiagnosed and add to the spread of disease.
Their study was published in PLoS Biology.
In treating infections with drugs, we change their environment, but bacteria and other infectious agents are incredibly good at adapting to their environment. Damage limitation therapies may be a useful alternative to antibiotics, but we should be cautious, and investigate their potential long-term consequences. Limiting damage may work for the individual, but could, in some cases, increase disease spread.
Dr Pedro Vale
School of Biological Sciences
Cost efficient way to develop safer compounds
From the 13 June 2012 Medical News Today article
A new set of computer models has successfully predicted negative side effects in hundreds of current drugs, based on the similarity between their chemical structures and those molecules known to cause side effects, according to a paper appearing online this week in the journal Nature. …
Drugs frequently interact with more than one target, with hundreds of these targets linked to the side effects of clinically used therapeutics. Focusing on 656 drugs that are currently prescribed, with known safety records or side effects, the team was able to predict such undesirable targets – and thus potential side effects – half of the time.
That’s a significant leap forward from previous work, which has never tackled hundreds of compounds at once, according to Brian Shoichet, PhD, a UCSF professor of pharmaceutical chemistry who was the joint advisor on the project alongside Laszlo Urban, MD, PhD, at Novartis.
As a result, it offers a possible new way for researchers to focus their efforts on developing the compounds that will be safest for patients, while potentially saving billions of dollars each year that goes into studying and developing drugs that fail. …
Drug Failure Rates
- Estimated cost of bringing a drug to market: $1.2 billion
- Only one in 5,000 drug candidates that enter preclinical testing ever reaches the market
- For every five drugs that start clinical trials, only one succeeds
- Of the 4,300 companies engaged in drug innovation, only 6% (261) have registered a new drug since 1950.
- Worldwide, the pharmaceutical industry spends $50 Billion per year on R&D, but produces only 21 new drugs per year (2008)
A Side Effect of Vicodin (Photo credit: thehoneybunny)
Drugs: ‘New’ does not always mean ‘better’
From the 2 March Science Daily article
Cases in which a newly approved drug is more effective than the cheaper alternatives already available are the exceptions rather than the rule.
This is the conclusion reached in a study by Mariam Ujeyl et al. in the current issue of Deutsches Ärzteblatt International.
Research into 39 proprietary medicinal products (PMPs) launched on the German market in 2009 and 2010 shows that there were frequently insufficient data available on efficacy when approval was granted. The legal requirements of the licensing procedure have never yet required direct data comparing a new drug to a commercially available drug.
The researchers’ evaluations also show that for around half of approvals the only trials presented compared the new drug with a placebo, not an effective comparator drug.
This can give rise to room for interpretation regarding pricing when new drugs are marketed. The authors do not even rule out the possibility that these more expensive PMPs may actually be inferior to the alternatives already on the market.
From the 15 December 2011 Medical News Today article
There are probably at least 500 medically useful chemicals awaiting discovery in plant species whose chemical constituents have not yet been evaluated for their potential to cure or treat disease, according to a new analysis by a New York Botanical Garden scientist who has more than 15 years of experience in collecting plants for natural-products discovery programs.
Currently, 135 drugs on the market are derived directly from plants; the analysis indicates that at least three times as many disease-fighting substances have yet to be found that could be developed into drugs or used as the basis for further drug research.
“Clearly, plant diversity has not been exhausted, and there is still great potential in the plant world,” said James S. Miller, Ph.D., Dean and Vice President for Science at the Botanical Garden.
Dr. Miller’s analysis, “The Discovery of Medicines from Plants: A Current Biological Perspective,” is published in the December issue of the peer-reviewed journal Economic Botany. …
[Web site of journal is here, for options on how to get the article for free or at low cost, click here]
Dr. Miller argues that one possible explanation for the low yield is the relatively crude way in which plant extracts were tested for their pharmaceutical potential. Plants may contain as many as 500 to 800 different chemical compounds, but the screening programs of the late 20th century used extracts made from a whole plant or at best extracts that contained many hundreds of compounds.
Under those circumstances, one compound may interfere with the action of another, or the amount of one compound may be too small to register in a mix of hundreds of chemicals.
To correct this problem, new technologies now allow researchers to separate complex mixtures of natural products into a “library” of relatively pure compounds that can be tested individually. A 2002 study demonstrated that testing such libraries dramatically improves discovery rates. …..
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