Health and Medical News and Resources

General interest items edited by Janice Flahiff

‘Person-on-a-chip’ — U of T engineers create lab-grown heart and liver tissue for drug testing and more [news release]

From the 7 March 2016 University of Toronto news release

Excerpts
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)

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)

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.

March 8, 2016 Posted by | Medical and Health Research News | , , , , , , | Leave a comment

[News release] Most Information in Drug Development Is Lost

From the 9 March 2015 Newswise article

Lots of potentially useful medical information is getting lost. McGill researchers discovered this when they looked into the lack of reporting of information from “stalled drug” trials in cancer, cardiovascular and neurological diseases.

“Stalled drugs” are drugs that fail to make it to the market either because they prove to be ineffective or unsafe or both. Because only one in ten of the drugs that goes into human testing actually gets licensed, most of the information collected in developing new drugs is currently being lost. This is despite the fact that this information is critical for effective care, protecting patients, and discovering better drugs.

….

Findings from trials of stalled drugs:

1. Allow drug developers to discover what didn’t work, and then adjust the compound or method of delivery so that it might work for other conditions. For example, the drug Viagra failed initially as a drug for treatment of angina. We now know it to be a very effective drug for erectile dysfunction.

2. Help us learn about the safety of other approved drugs. Often, trials of experimental drugs generate valuable evidence about the safety of approved drugs – especially if the approved drugs are in the same chemical family.

3. Help drug discoverers learn about the limits of animal models and other experimental techniques. “When a drug works in animal models but not in patients, we have an opportunity to study why our model fell short and to improve it,” says Amanda Hakala, a Master’s student who is first author on the study.

4. Contain safety and efficacy information that might be useful in other parts of the world. Often, drugs that are considered unsafe and ineffective in one part of the world are approved in another. “Failure to publish these trials deprives patients in those other jurisdictions of state of the art evidence of safety and efficacy,” says Kimmelman.

March 10, 2015 Posted by | Medical and Health Research News | , , , | Leave a comment

[Press release] MD Anderson and Bayer collaborate to create symptom assessment questionnaires in clinical trials

MD Anderson and Bayer collaborate to create symptom assessment questionnaires in clinical trials 

From the press release

MD Anderson News Release 1/23/2015

When cancer patients take part in a clinical trial to develop new therapies, they and their physicians want to know how they will feel and function during treatment. A new collaboration between Bayer and The University of Texas MD Anderson Cancer Center will go straight to the patients to learn how certain investigational new drugs affect them. The project will involve the use of questionnaires to assess how a drug may impact a patient’s disease-related symptoms.

“Fit-for-purpose patient-reported-outcome (PRO) measures are an invaluable resource for helping us to better understand how patients are actually being affected by new therapies,” said Charles Cleeland, Ph.D., chair of symptom research at MD Anderson. “This will be especially important in the developmental pathway of new drugs, given that these PRO measures will enhance information about treatment tolerability and potential symptom-reduction benefit earlier in the drug development process.”

Charles Cleeland, Ph.D.

The information will be beneficial in further evaluating the drug if it progresses to later stages of clinical development and is tested in larger numbers of patients. The importance of having data on the symptom burden or benefit conferred by therapy is often not recognized until late in that process.

“For patients and their physicians, knowing the probable effects of a treatment can help with decisions among treatment options when therapeutic outcomes are similar but symptomatic effects are not,” said Cleeland.

 Related Resources

  • ClinicalTrials.gov
    • registry and results database of publicly and privately supported clinical studies of human participants conducted around the world
    • What Information Can I Find on ClinicalTrials.gov?

      Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following:

      • Disease or condition
      • Intervention (for example, the medical product, behavior, or procedure being studied)
      • Title, description, and design of the study
      • Requirements for participation (eligibility criteria)
      • Locations where the study is being conducted
      • Contact information for the study locations
      • Links to relevant information on other health Web sites, such as NLM’s MedlinePlus® for patient health information and PubMed® for citations and abstracts for scholarly articles in the field of medicine.

      Some records also include information on the results of the study, such as:

      • Description of study participants (the number of participants starting and completing the study and their demographic data)
      • Outcomes of the study
      • Summary of adverse events experienced by study participants
    • More information at ClinicalTrials.gov

January 26, 2015 Posted by | Health News Items | , , , , , , | Leave a comment

[News article] Understanding natural compounds when antibiotics no longer work — ScienceDaily

Understanding natural compounds when antibiotics no longer work — ScienceDaily.

Excerpts

Date:November 12, 2014
Source:ETH Zürich
Summary:Medicine is drifting towards a major problem. An increasing number of bacteria is no longer sensitive to known antibiotics. Doctors urgently need to find new ways of fighting these multi-resistant pathogens. To address the problem, pharmaceutical research is turning back to the source of most of our drugs: nature.

Although hundreds of thousands of known active agents are found in nature, exactly how most of them work is unclear. A team of researchers from ETH Zurich has now developed a computer-based method to predict the mechanism of action of these natural substances. The scientists hope this method will help them to generate new ideas for drug development. “Natural active agents are usually very large molecules that often can be synthesized only through very laborious processes,” says Gisbert Schneider, a professor of computer-aided drug design at the Institute of Pharmaceutical Sciences at ETH Zurich. An understanding of the exact mechanism of action of a natural substance enables the design of smaller, less complex molecules that are easier to synthesize. Once a substance is chemically synthesized, it can be optimized for medical applications.

In order to understand the mechanism of action, researchers are studying which parts of a pathogen interact with the natural substance to inhibit its growth for example. In the past, this involved highly complex laboratory tests through which scientists usually identified only the strongest effect of a substance. However, this interaction alone is often unable to explain the entire effect of a natural substance. “Minor interactions with other target structures can contribute to the overall effect as well,” explains Schneider.

“By using the computer to break down the molecules, which can be quite large, into separate building blocks, we discover which parts might be essential for the mechanism of action,” says Schneider. Thus, it might be possible to design less complex molecules that chemists could synthesize instead of the laborious process of isolating them from the natural source.

Analysis of 210,000 natural substances

Using the computer-based method, the researchers led by Gisbert Schneider were able to predict a variety of potential target structures for 210,000 known natural substances.

November 14, 2014 Posted by | Medical and Health Research News | , , , , | Leave a comment

[Repost] Database of Disease Genes Shows Potential Drug Therapies

From the 10 October 2013 article at newswise 

            [From the  article abstract – The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially ‘druggable’ genes. DGIdb can be accessed at http://dgidb.org/.]

Newswise — Researchers at Washington University School of Medicine in St. Louis have created a massive online database that matches thousands of genes linked to cancer and other diseases with drugs that target those genes. Some of the drugs are approved by the U.S. Food and Drug Administration, while others are in clinical trials or just entering the drug development pipeline.

The database was developed by identical twin brothers, Obi Griffith, PhD, and Malachi Griffith, PhD, whose interest in pairing drugs with genes is as much personal as it is scientific. Their mother died of breast cancer 17 years ago, just weeks before their high school graduation.

“We wanted to create a comprehensive database that is user-friendly, something along the lines of a Google search engine for disease genes,” explained Malachi Griffith, a research instructor in genetics. “As we move toward personalized medicine, there’s a lot of interest in knowing whether drugs can target mutated genes in particular patients or in certain diseases, like breast or lung cancer. But there hasn’t been an easy way to find that information.”

Details of the Drug Gene Interaction database are reported online Oct. 13 in Nature Methods. The database is weighted heavily toward cancer genes but also includes genes involved in Alzheimer’s disease, heart disease, diabetes and many other illnesses. The Griffiths created the database with a team of scientists at The Genome Institute at Washington University in St. Louis.

The database is easy to search and geared toward researchers and physician-scientists who want to know whether errors in disease genes – identified through genome sequencing or other methods – potentially could be targeted with existing drug therapies. Additional genes included in the database could be the focus of future drug development efforts because they belong to classes of genes that are thought to make promising drug targets.

“Developing the database was a labor of love for the Griffiths,” said senior author Richard K. Wilson, PhD, director of The Genome Institute. “There’s an amazing depth to this resource, which will be invaluable to researchers working to design better treatment options for patients.”

Wilson and his colleagues caution that the database is intended for research purposes and that it does not recommend treatments. The primary purpose of the database is to further clinical research aimed at treating diseases more effectively.

“This database gets us one step closer to that goal,” Malachi Griffith said. “It’s a really rich resource, and we’re excited to make it available to the scientific community.”

The database, which took several years to develop, is publicly available and free to use. It includes more than 14,000 drug-gene interactions involving 2,600 genes and 6,300 drugs that target those genes. Another 6,700 genes are in the database because they potentially could be targeted with future drugs.

Before now, researchers wanting to find out whether disease genes could be targeted with drugs had to search piecemeal through scientific literature, clinical trials databases or other sources of information, some of which were not publicly available or easily searchable. Further, many of the existing databases have different ways of identifying genes and drugs, a “language” barrier that can turn a definitive search into an exhaustive exercise.

The Griffith brothers are experts in bioinformatics, a field of science that integrates biology and computing and involves analyzing large amounts of data. The brothers got the idea for the drug-gene interaction database after they repeatedly were asked whether lists of genes identified through cancer genome sequencing could be targeted with existing drugs.

“It shouldn’t take a computer wizard to answer that question,” said Obi Griffith, research assistant professor of medicine. “But in reality, we often had to write special software to find out. Now, researchers can quickly and easily search for themselves.”

The new database brings together information from 15 publicly available databases in the United States, Canada, Europe and Asia. Users can enter the name of a single gene or lists of many genes to retrieve drugs targeting those genes. The search provides the names of drugs targeted to each gene and details whether the drug is an inhibitor, antibody, vaccine or another type. The search results also indicate the source of the information so users can dig deeper, if they choose.

The research is supported by a grant (U54 HG003079) from the National Human Genome Research Institute at the National Institutes of Health (NIH).

Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC, Koval J, Das I, Callaway MB, Eldred JM, Miller CA, Subramanian J, Govindan R, Kumar RD, Bose R, Ding L, Walker JR, Larson DE, Dooling DJ, Smith SM, Ley TJ, Mardis ER and Wilson RK. DGIdb – Mining the druggable genome. Nature Methods. Oct. 13, 2013.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare​.

 

October 15, 2013 Posted by | Consumer Health, Medical and Health Research News | , , , , , | Leave a comment

   

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