Mice with glioblastomas that were treated with TIC10 in combination with bevacizumab#a drug used against diseases including brain tumours
because it is much smaller than proteins that have previously been tested as TRAIL-based drugs.
but can also thwart anticancer drugs by keeping them out.""We didn t actually anticipate that this molecule would be able to treat brain tumours#that was a pleasant surprise,
In particular, cancer researchers have been developing a number of drugs, including TRAIL-based therapeutics, that work by activating the cellular messenger tumour protein 53 (p53).
Many large biomedical research groups have shelved their TRAIL-based drugs L
#Europe bets on drug discovery Two sites shuttered by the pharmaceutical giant Merck, one in Scotland and one in The netherlands, will soon be humming again with the work of drug discovery.
But the hum will not be business as usual. It will be the sound of a public-private consortium placing a high-stakes wager:
a nearly##200-million (US$271-million) bet that it can boost a languishing pharmaceutical sector by fusing academic innovation with industrial-scale screening,
and aims to fill company pipelines with promising drug candidates. The current dearth of candidates
the pharmaceutical partners will be able to use the library#including molecules from their competitors#in their own drug screens.
such as tumour shrinkage, that the compounds may work as drugs. These molecules can then be licensed back to companies for further development.
The scheme hopes to become self-sustaining by requiring milestone payments as drugs move from laboratory to clinic and from additional partnerships and screening services."
but its goal was not to find potential drugs but to identify biological pathways that might make good drug targets.
The European initiative, by contrast, aims to propel drug development. Both the chemicals in the screening library and results from the assays will be proprietary.
Factory partners will get first right of refusal in licensing deals. Such restrictions are essential
if a compound is ever going to make the long journey from a screening hit to a viable drug candidate,
"To justify the subsequent investments you have to make in hit-to-drug lead programmes,
and focusing on specific drug mechanisms makes his consortium s approach much simpler.""Intellectual-property deals, assays coming from everywhere, multi-institutional agreements.
#Scientists map protein that creates antibiotic resistance Japanese researchers have determined the detailed molecular structure of a protein that rids cells of toxins,
but can also reduce the effectiveness of some antibiotics and cancer drugs by kicking them out of the cells they are targeting.
The discovery suggests new approaches to combat antibiotic resistance and boost the power of cancer therapies,
That s a promising proof of concept for creating a MATE-blocking drug because the inhibitory peptide can do its job without having to enter cells,
#Serotonin receptors offer clues to new antidepressants Researchers have deciphered the molecular structures of two of the brain's crucial lock-and-key mechanisms.
appetite and mood#and could provide targets for future drugs to combat depression, migraines or obesity.#"
they might now be able to make breakthroughs in drug discovery and in understanding how the physical structures of the brain produce consciousness,
Christoph Anacker, a neuropharmacologist at King's college London, agrees that the findings are important for drug discovery."
when drugs or neurotransmitters lock into the receptors from outside the cell, they trigger the release of other chemicals inside the cell.
Some drugs bind at more than one receptor, setting off not-fully-understood reactions that can produce unwanted side effects.
To avoid this, researchers want to fine-tune drugs so that they activate only the desired signalling pathway.
some drugs that activate the 2b receptor have been thought to cause heart problems3, and have been withdrawn as unsafe.
They triggered both 1b and 2b with the powerful psychedelic drug LSD and one of its precursors, a migraine drug called ergotamine.
The drugs produced two different chemical cascades#G-protein and ß-arrestin#from the 1b receptor,
Rosenberg points to a collaboration formed in August last year between June's group and the drug giant Novartis,
With further development, the authors say the technology might one day be used for visualisation of the shapes of molecules used in drug development,
or to test the effects of drugs on individual cells. A transistor acts like a switch in an electrical circuit:
He also hopes to test the effects of candidate drugs on the metabolism of human cells, by monitoring ph changes, for example."
because the path from a genetic-disease marker to a profitable drug has not been straight#forward.
or precisely deliver drugs to a particular area when they are needed. No one device can do all of these things simultaneously,
to have an implant with electrodes paired with drug delivery pumps that could sense an oncoming epileptic seizure
which could revolutionize drug discovery and personalized medicine. In a laboratory first, Duke researchers have grown human skeletal muscle that contracts
The lab-grown tissue should soon allow researchers to test new drugs and study diseases in functioning human muscle outside of the human body.
Bursac and Madden studied its response to a variety of drugs, including statins used to lower cholesterol and clenbuterol,
a drug known to be used off-label as a performance enhancer for athletes. The effects of the drugs matched those seen in human patients.
The statins had a dose-dependent response, causing abnormal fat accumulation at high concentrations. Clenbuterol showed a narrow beneficial window for increased contraction.
and experiment to see which drugs would work best for each person. This goal may not be far away;
Bursac is already working on a study with clinicians at Duke Medicinencluding Dwight Koeberl, associate professor of pediatricso try to correlate efficacy of drugs in patients with the effects on lab-grown muscles.
Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle
In response to diversely acting drugs myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes.
Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders. ioengineered human myobundles mimic clinical responses of skeletal muscle to drugsby Lauran Madden, Mark Juhas, William
might instead arise from ongoing alterations in synaptic signaling that can be corrected by drugs. Current research indicates that well over 100 distinct gene mutations can manifest as intellectual disability and autism.
as they indicate not only that drug therapies might be effective to improve cognition and behavior in affected individuals,
The findings may one day lead to drugs or other interventions that would lessen the effects of the mutations,
According to the UCSF scientists, their unexpected new findings could reshape basic research on feeding behavior as well as strategies for the development of new anti-obesity drugs.
what we might be manipulating with drugs targeting Agrp pathways. We might be manipulating the decision to go to the grocery store,
but that they can help pinpoint key biological pathways relevant to ALS that then become the focus of targeted drug development efforts,
and mouse models with mutations in TBK1 or OPTN to study ALS disease mechanisms and to screen for drug candidates.
extending the range of options for future drug development. The research was carried out by an international team comprising academics from the Department of chemistry at the University of Cambridge, the Karolinska Institute in Stockholm, Lund University, the Swedish University of Agricultural sciences,
Their discovery suggests that drugs designed to target NHE9 could help to successfully fight the deadly disease.
Drugs targeting EGFR in these patients are sometimes effective. As they suspected, the team found that alkaline endosomes slow down the removal of EGFR from cell surfaces.
when treated with both a drug countering NHE proteins and a drug against EGFR than when treated by the EGFR-targeting drug alone.
Quinones-Hinojosa says: e are still five to 10 years away from testing this idea in patients,
#Gene Breakthrough Sparks Fear of Homemade Morphine Scientists on Monday said they had unlocked a pathway for producing opiates from genetically engineered yeast
but feared the discovery could one day be a bonanza for drug lords. Other experts agreed, saying anyone with basic skills could use such a yeast to churn out morphine,
codeine and drugs using a simple home-brew beer kit. The discovery, published in the scientific journal Nature Chemical Biology, comes on the heels of a study published last month in the journal PLOS ONE.
Together, the papers describe key steps towards bioengineering yeast that would feed on sugar and exude opiates and other therapeutic drugs.
The goal is to provide cheaper and possibly less addictive painkillers from a dependable source as compared to the poppy.
"meaning it is the springboard for making morphine, codeine and oxycodone, as well as antispasmodic drugs like papaverine.
The team did not go on to make these drugs, but the process of going from reticuline to codeine
and morphine in yeast is known already. What had been missing in the knowledge chain was getting from tyrosine to reticuline.
The discovery may be a boon in pharmaceutics but it also"dramatically speeds up the clock for
when home-brewing drugs could become a reality, "the researchers cautioned.""We're likely looking at a timeline of a couple of years, not a decade or more,
the trio said the way was now open for engineering a yeast strain that would do the whole drug-making trick.
and basic skills in fermentation would be able to grow morphine-producing yeast using a home-brew kit for beer-making,
"If the modified yeast strain produced 10 grams of morphine, users would need to drink only one to two milliliters of the liquid to obtain a standard prescribed dose."
"In addition to tighter lab security and tougher laws, the trio called for yeast strains to be engineered to produce drugs with limited street value,
It could be, for all intents and purposes, the world first digital drug. Will Shanklin of Gizmag first tried Thync at the Consumer electronics Show in January 2015
the electric field can directly couple to the electric circuitry of the neural network. he nanoparticles could be used to deliver drugs to specific parts of the brain.
and anticancer drugs could be delivered and released in this way. Wearable device Changes Your Moodthe technique could also be used to create a new kind of brain-computer interface.
#'Edible Barcodes'Help Fight Counterfeit Drugs Who knew that the answer to fighting the trillion-dollar global counterfeit drug problem rested in a particle the size of a speck of dust?
edible barcodes that can be planted right onto medicine to verify that the pills and tablets you might consume are the real deal.
Essentially, a drug that has one of these microscopic ignaturescould easily be identified as genuine and not a fake.
they consume 40 percent of all prescription drugs and 35 percent of all over-the-counter drugs.
and the nurse comes in with a cup that has seven pills in it. They are out of the package in the cup and there all of these morning pills together,
Wuh said. magine a hospital setting in the future where every one of these pills will be identified, where you could do a few-seconds scan that can tell you which pill is what,
if theye genuine or authentic, when they expired, what the drug interaction would be. With that information you are back in control think how powerful that is. or Wuh
who also has a Masters of Public health degree from Harvard university, a big component of this company is to empower consumers to understand what they are putting into their bodies,
and as a result, make better health decisions. e want to be able to watch these billions of items that are present in daily life
Wuh said the idea of tiny microscopic particles containing data about a drug is farfetched no more than someone 20 years ago saying that a person would have a upercomputer the size of his palm. ut,
whether or not a drug is a counterfeit is eally quite tedious. For example, say law enforcement seizes
what is perceived to be a counterfeit of a drug like Sovaldi, which is used to treat hepatitis.
The law enforcement has to ship it by express mail to a lab that then has to process the drug and run a series of tests.
and can aid in evaluating heart drugs for safety, particularly for pregnant women. The tiny hearts could also serve as models to treat damaged hearts.
When a researcher asked all three robots which pill they had received the one that was muted not responded,
I was given not a dumbing pill. You can watch the impressive exhibit unfold here. The robot demonstrated the ability to understand the contest rules,
#Microbe found in grassy field contains powerful antibiotic For much of the last decade, a team of researchers in Boston has exhumed eagerly
the compound is unlikely to fall prey to the problem of antibiotic resistance. That suggestion has its skeptics,
but if the drug makes it through clinical trials, it would be needed a much weapon against several increasingly hard-to-treat infections.
Many existing antibiotics, including penicillin, were identified by cultivating naturally occurring microorganismsacteria often try to kill each other with chemical warfare,
To test the antibacterial properties of these soil microbes, the team let each of them duel in a lab dish with Staphylococcus aureus, a cause of serious skin and respiratory infections.
when a small percentage of microbes escape an antibiotic because of a mutation and then those bacteria multiply.)
Bleach, after all, is a strong antibiotic, but it a little too effective at killing any surrounding cells.)
And it showed other qualities of a good antibiotic, the team reports online in Nature.
a drug long relied upon to treat the obstinate methicillin-resistant Staphylococcus aureus (MRSA), by a factor of 100,
increasingly feared in hospitals for their resistance to existing drugs. But the authors suggest it could be of great value to people fighting MRSA, tuberculosis,
and infections with rare-but-nasty Enterococcus bacterial strains that aren responding to available drugs.
who studies how bacteria become susceptible to antibiotics. his study demonstrates that unculturable bacteria have unrecognized new,
when exposed to drugs. A demonstration of the approach, published online today in the Proceedings of the National Academy of Sciences
The dance of levitating cells can also carry information about how well a drug works.
Researchers could identify which individual cellsrom a tumor or a strain of bacteriaurvive a drug treatment and study them further, something that's not possible with current culture-and-stain tests,
or antiretroviral (ARV) drugs. eservoirsof infected cells that hold latent provirus are a key reason why powerful combinations of ARVS cannot eliminate infections and cure people.
or determine whether drugs have reached successfully their targets. In a paper appearing in the Nov 18 issue of Nature Communications the researchers demonstrate the use of the particles which carry distinct sensors for fluorescence
They have created also nanoparticles carrying the fluorescent agent plus up to three different drugs. This allows them to track
For example in this study the new DNA sequence turned on an antibiotic resistance gene allowing the researchers to determine how many cells had gotten the memory sequence by adding antibiotics to the cells
and an antibiotic derivative called atc but it could be tailored to many other molecules or even signals produced by the cell Lu says.
and based on natural or engineered microorganisms that have higher efficacy and fewer side effects than conventional drug treatments.
when we deliver the drug locally. The paper s other senior authors are Robert Langer the David H. Koch Institute Professor at MIT
Targeted deliverychemotherapy drugs are delivered usually via intravenous injection. To make sure that enough reaches a tumor very large quantities must be given often producing side effects.
when drugs are delivered directly into the abdominal cavity. However this is not widely done because it requires implanting a catheter in the patient for 12 weeks
To overcome these delivery issues Cima s lab is working on small implantable devices to deliver drugs for ovarian cancer and bladder disease as well as brain cancer.
The capsules are small cylinders with a 1. 5-milliliter drug capacity; the drug diffuses out through a small hole.
These are experimental devices the researchers selected to test whether the concept of local delivery would work
The properties of the drug molecule have to be taken into account in the design of local therapy that s effective says Cima.
The researchers are also working on using this approach to precisely deliver drugs to very small regions of the brain in hopes of developing better treatments for psychiatric and neurodegenerative disorders.
They envision using this technique to create mice with tumors carrying the same genetic profile as a patient then testing different drugs on them to see which have the best effect.
which causes painful and frequent urination that can interrupt daily life currently requires infusing the drug lidocaine into a patient bladder through a catheter.
But Taris now plans to tailor the platform device to carry other drugs into the bladder to treat various diseases,
the researchers developed a prototype device by using a laser to cut a hole in a silicone tube to add drugs. ight
Moreover, the researchers proved that drugs injected slowly into the bladder for so long could actually be absorbed.
Surprise findings Tarisfirst trial involved implanting an empty device (with no drugs) inside volunteers to test comfort levels.
With the Allergan acquisition funds, Taris will further develop the device to deliver drugs for other bladder diseases,
to difficulties delivering drugs in a sustained way. Last year, Taris entered a research collaboration with Astrazeneca to develop novel treatments for bladder cancer. his device is a platform
overactive or underactive bladder any of these indications where you might want to deliver drugs right to the bladder it can do that.
A member of the MIT Koch Institute, Cima is also working on other drug-delivery projects,
#High-speed biologics screen MIT engineers have devised a way to rapidly test hundreds of different drug-delivery vehicles in living animals making it easier to discover promising new ways to deliver a class of drugs called biologics
because they are significantly larger and more complex than conventional drugs. By combining this work with our previously published high-throughput screening system we are able to create a drug-discovery pipeline with efficiency we had imagined never before adds Tsung-Yao Chang a recent MIT Phd recipient and one of the paper s lead authors.
Peng Shi a former MIT postdoc who is now an assistant professor at the University of Hong kong is the paper s other lead author.#
because their larvae are transparent making it easy to see the effects of genetic mutations or drugs.#
and in zebrafish was 97 percent suggesting that zebrafish are a good model for predicting drug-delivery success in mammals.#
#The ability to identify useful drug delivery nanoparticles using this miniaturized system holds great potential for accelerating our discovery process Anderson says.
Yanik s lab is currently using this technology to find delivery vehicles that can carry biologics across the blood-brain barrier a very selective barrier that makes it difficult for drugs
or chemical agents to drug interdiction discovery of stress fractures in submerged structures and hulls or even faster processing
#Battling superbugs In recent years new strains of bacteria have emerged that resist even the most powerful antibiotics.
Each year these superbugs including drug-resistant forms of tuberculosis and staphylococcus infect more than 2 million people nationwide
Despite the urgent need for new treatments scientists have discovered very few new classes of antibiotics in the past decade.
Using a gene-editing system that can disable any target gene they have shown that they can selectively kill bacteria carrying harmful genes that confer antibiotic resistance or cause disease.
Last month Lu s lab reported a different approach to combating resistant bacteria by identifying combinations of genes that work together to make bacteria more susceptible to antibiotics.
Lu hopes that both technologies will lead to new drugs to help fight the growing crisis posed by drug-resistant bacteria.
when there are fewer and fewer new antibiotics available but more and more antibiotic resistance evolving he says.
We ve been interested in finding new ways to combat antibiotic resistance and these papers offer two different strategies for doing that.
Cutting out resistancemost antibiotics work by interfering with crucial functions such as cell division or protein synthesis. However some bacteria including the formidable MRSA (methicillin-resistant Staphylococcus aureus)
and CRE (carbapenem-resistant Enterobacteriaceae) organisms have evolved to become virtually untreatable with existing drugs. In the new Nature Biotechnology study graduate students Robert Citorik and Mark Mimee worked with Lu to target specific genes that allow bacteria to survive antibiotic treatment.
The CRISPR genome-editing system presented the perfect strategy to go after those genes. CRISPR originally discovered by biologists studying the bacterial immune system involves a set of proteins that bacteria use to defend themselves against bacteriophages (viruses that infect bacteria.
One of these proteins a DNA-cutting enzyme called Cas9 binds to short RNA guide strands that target specific sequences telling Cas9 where to make its cuts.
They designed their RNA guide strands to target genes for antibiotic resistance including the enzyme NDM-1
which allows bacteria to resist a broad range of beta-lactam antibiotics including carbapenems. The genes encoding NDM-1 and other antibiotic resistance factors are carried usually on plasmids circular strands of DNA separate from the bacterial genome making it easier for them to spread through populations.
When the researchers turned the CRISPR system against NDM-1 they were able to specifically kill more than 99 percent of NDM-1-carrying bacteria while antibiotics to
which the bacteria were did resistant not induce any significant killing. They also successfully targeted another antibiotic resistance gene encoding SHV-18 a mutation in the bacterial chromosome providing resistance to quinolone antibiotics and a virulence factor in enterohemorrhagic E coli.
In addition the researchers showed that the CRISPR system could be used to selectively remove specific bacteria from diverse bacterial communities based on their genetic signatures thus opening up the potential for microbiome editing beyond antimicrobial applications.
To get the CRISPR components into bacteria the researchers created two delivery vehicles engineered bacteria that carry CRISPR genes on plasmids
Both of these carriers successfully spread the CRISPR genes through the population of drug-resistant bacteria.
This work represents a very interesting genetic method for killing antibiotic-resistant bacteria in a directed fashion
which in principle could help to combat the spread of antibiotic resistance fueled by excessive broad-spectrum treatment says Ahmad Khalil an assistant professor of biomedical engineering at Boston University who was not part of the research team.
High-speed genetic screensanother tool Lu has developed to fight antibiotic resistance is called a technology Combigem. This system described in the Proceedings of the National Academy of Sciences the week of Aug 11 allows scientists to rapidly
and systematically search for genetic combinations that sensitize bacteria to different antibiotics. To test the system Lu
The researchers then delivered the gene pairs into drug-resistant bacteria and treated them with different antibiotics.
For each antibiotic they identified gene combinations that enhanced the killing of target bacteria by 10000-to 1000000-fold.
The researchers are now investigating how these genes exert their effects. This platform allows you to discover the combinations that are really interesting
Once scientists understand how these genes influence antibiotic resistance they could try to design new drugs that mimic the effects Lu says.
#An end to drug errors? MIT alumni entrepreneurs Gauti Reynisson MBA 10 and var Helgason HS 08 spent the early 2000s working for companies that implemented medication-safety technologies
such as electronic-prescription and pill-barcoding systems at hospitals in their native Iceland and other European countries.
Indeed a 2006 report from the Institute of Medicine found that 1. 5 million hospitalized patients in the United states experience medication errors every year due in part to drug-administration mistakes.
and devised Medeye a bedside medication-scanning system that uses computer vision to identify pills
and check them against medication records to ensure that a patient gets the right drug and dosage.
The nurse then pushes the assigned pills into the Medeye via a sliding tray. Inside the device a small camera scans the pills rapidly identifying them by size shape color and markings.
Algorithms distinguish the pills by matching them against a database of nearly all pills in circulation.
Although the hardware is impressive much innovation is in Medeye s software which cross-references (and updates) the results in the patient s records.
if pills have been prescribed correctly (green) or are unknown or wrong (red). If a pill isn t in Medeye s database
because it s new for instance the system alerts the nurse who adds the information into the software for next time.
and then the imprinted barcodes on each pill container. But the hurdle has been getting these installed Reynisson says.
The nurse scanned four pills which had been assigned to the patient and added an extra erroneous pill to show how Medeye caught errors.
Medeye showed the extra pill was incorrect. But to his surprise so were two other pills that the nurse had assumed were correct
because another nurse had dispensed those Reynisson says. Goes to show that even with full focus it is common for nurses to be in a position where they are expected to catch errors made in other parts of the medication-delivery process.
Vision for new technologyhelgason conceived of Medeye while studying in the MIT-Harvard Health Sciences and Technology program.
The hospital had to identify about 250 small white pills of different medications that in fact all looked the same.
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011