Synopsis: Pharma: Drugs:


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#Versatile antibiotic found with self-immunity gene on plasmid in staph strain A robust broad spectrum antibiotic

and a gene that confers immunity to that antibiotic are both found in the bacterium Staphylococcus epidermidis Strain 115.

The antibiotic a member of the thiopeptide family of antibiotics is not in widespread use partly due to its complex structure

and derivitization so that new and possibly more potent versions of the antibiotic can become available says co-corresponding author Joel S. Griffitts.

It quickly became clear to the investigators that Strain 115 could produce a potent antibiotic that targets a large number of medically relevant bacteria including those that cause staph infections strep throat and severe gastrointestinal diseases.

We wanted to know the identity of this antibiotic and the means by which Strain 115 protects itself from its own antibiotic's deadly effects says Griffitts.

We found that the genes for both antibiotic synthesis and self protection in Strain 115 are clustered conveniently on a compact DNA molecule a plasmid that replicates itself as a small circle within the cells of Strain 115 says Griffitts.

Among experiments they conducted to prove this they engineered a version of Strain 115 that was missing the plasmid.

That version failed to produce both the antibiotic and the immunity to the antibiotic. The investigators then analyzed the mechanism of immunity.

Thiopeptide antibiotics kill cells by blocking a part of the ribosome Griffitts explains. Ribosomes common to all living organisms are the machines that read the genetic code producing proteins based on the instructions therein.

The plasmid which directs the production of the thiopeptide antibiotic also directs production of a spare part for the ribosome a replacement for the part that is blocked by the antibiotic

which renders the ribosome insensitive to the antibiotic. The investigation of Strain 115 began as an undergraduate project after the bacteria had sat in a laboratory freezer for decades says Griffitts.

Hopefully he says the research will ultimately enable production of a valuable antibiotic in quantities sufficient to make a dent in the antibiotic crisis. Story Source:


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#Bio-inspired nano-cocoons offer targeted drug delivery against cancer cells Biomedical engineering researchers have developed a drug delivery system consisting of nanoscale ocoonsmade of DNA that target cancer cells

and trick the cells into absorbing the cocoon before unleashing anticancer drugs. The work was done by researchers at North carolina State university

and the University of North carolina at Chapel hill. his drug delivery system is based DNA which means it is biocompatible

Chapel hill. his technique also specifically targets cancer cells can carry a large drug load and releases the drugs very quickly once inside the cancer cellgu says. n addition

because we used self-assembling DNA techniques it is relatively easy to manufacturesays Wujin Sun lead author of the paper

The core of the nano-cocoon contains the anticancer drug doxorubicin (DOX) and a protein called DNASE.

and think it holds promise for delivering a variety of drugs targeting cancer and other diseases. he paper ocoon-Like Self-Degradable DNA-Nanoclew for Anticancer Drug Deliverywas published online Oct 13 in the Journal


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or in sunscreen lotions to absorb harmful ultraviolet rays. Naturally found in a spherical shape NTU Singapore developed a simple method to turn titanium dioxide particles into tiny nanotubes that are a thousand times thinner than the diameter of a human hair.


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They developed a new surface coating for medical devices using materials already approved by the Food and Drug Administration (FDA.


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#Longer-term outcomes of program to reduce unnecessary antibiotic prescriptions The initial benefits of an outpatient antimicrobial stewardship intervention designed to reduce the rate of inappropriate antibiotic prescriptions were lost after discontinuation of audit

Antibiotics are the most frequently prescribed medications for children; most are prescribed for outpatient acute respiratory tract infections.

Because antibiotic prescribing is often inappropriate Jeffrey S. Gerber M d. Ph d. of Children's Hospital of Philadelphia

and colleagues recently conducted a randomized trial of an outpatient antimicrobial stewardship intervention that found a nearly 50 percent relative reduction in prescribing rates for broad-spectrum antibiotics according to background information in the article.

To assess the durability of this intervention the researchers followed antibiotic prescribing across intervention and control sites after termination of audit and feedback.

and audit and feedback of antibiotic prescribing. Nine practices received the intervention and 9 practices received no intervention.

Twelve months after initiating the study the researchers stopped providing antibiotic prescribing audit and feedback to clinicians in the intervention group.

and feedback broad-spectrum antibiotic prescribing decreased from 26.8 percent to 14.3 percent among intervention practices vs 28.4 percent to 22.6 percent in controls.

Following termination of audit and feedback however prescribing of broad-spectrum antibiotics increased over time reverting to above-baseline levels After restandardization of the data set for the additional 18 months of data antibiotic prescribing increased from 16.7 percent

and that antimicrobial stewardship requires continued active efforts to sustain initial improvements in prescribing. Our findings suggest that extending antimicrobial stewardship to the ambulatory setting can be effective

but should include continued feedback to clinicians the authors write. Story Source: The above story is provided based on materials by The JAMA Network Journals.


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so drugs targeting STAT3 could be used in cancer therapy. However STAT3 is also important in the development of the immune system.


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Many cholesterol treatments currently in development rely on an injection, not a pill. With the option of an orally effective peptide, Ghadiri believes researchers are closer to developing an accessible new therapy for atherosclerosis.


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#The dwindling stock of antibiotics, and what to do about it Michael Kinch Phd associate vice chancellor and director of the Center for Research Innovation in Business is among that number.

and then a second antibiotic while they worked on a diagnosis. They soon learned his son's appendix had burst

and was put on four newer antibiotics. When the lab tests for antibiotic susceptibility finally came in they showed the pathogenic bacteria were susceptible to only two of the six antibiotics Kinch's son had been given.

Stunningly the two that worked were the older drugs he had been given at the clinic. I can only assume that

if we had gone straight to the academic medical center he might not have survived Kinch said. It's not that my son had had extensive exposure to antibiotics Kinch explained carefully.

We're all just colonized by resistant bacteria now. Three weeks later I was asked to join a nonprofit organization working on new models for drug development called the Institute for Life sciences Collaboration Kinch said.

The institute was picking the therapeutic areas that would be their focus. They were considering various exotic diseases

and I said'Antibiotics.''Antibiotics are crashingin his last position as managing director of the Center for Molecular Discovery at Yale university Kinch had assembled a huge database of information about drug discovery and development in the pharmaceutical industry.

He has been able to excavate story after story from this storehouse of data. The crash of antibiotics is one of the best known and scariest

since losing antibiotics would force changes in almost every area of medical practice. In an article in Drug Discovery Today Kinch summarized the financial constraints that have led to the current crisis in antibiotic supply.

The number of antibiotics available for clinical use Kinch said has declined to 96 from a peak of 113 in 2000.

The rate of withdrawals is double the rate of new introductions Kinch said. Antibiotics are being withdrawn

because they don't work anymore because they're too toxic or because they've been replaced by new versions of the same drug.

Introductions are declining because pharmaceutical companies are leaving the business of antibiotic discovery and development. Pfizer or its predecessors developed 40 of the 155 antibiotics ever sold in this country Kinch said

but is no longer in the antibiotic space. Eli lilly Astrazeneca and Bristol-myers squibb have also left the antibiotic field

which is now dominated by small companies such as Cubist Pharmaceuticals formed in 1992 specifically to focus on drugs for resistant bacterial infections that could have higher price points.

His count Kinch said if anything overestimates the number of antibiotics still available because some of the new drugs are not general-purpose antibiotics.

They include for example an acne medication and a treatment for anthrax developed for use in case of a bioterrorist attack.

One reason pharmaceutical companies are said withdrawing Kinch is that our patent law squeezes them for time.

A patent gives a company 20 years of protection for a new drug but it takes 11 years of clinical trial experience on average to get a drug approved.

That means the typical company has nine years under patent to earn back the development costs before a generic comes in.

If the drug is an antibiotic there is an additional catch. Because of rising resistance doctors hold new antibiotics in reserve using them only in cases of dire need.

This happened for example in the case of vancomycin which has long been used as a drug of last resort.

When you hold a drug in reserve Kinch said you're eating into the patent time a company has to recoup its development costs.

If you've got this vancomycin-like situation where the drug is sitting on a shelf--quite literally sitting on a shelf--how is a company going to make its money back?

It can't price the drug at $10000 a dose. Companies have decided consistently there is no exit from this trapas long as we hold to the current model for drug development.

What to do about it? In the U s. we're used to turning to the NIH to solve problems like this

but the NIH budget which doubled in 2009 has fallen continuously ever since. It is now 30 percent below 2009 levels in constant dollars.

Since the NIH has fallen victim to congressional gridlock people in the biomedical community are starting to organize on their own.

The group Kinch helped found the Institute for Life sciences Collaboration recently convened an expert panel at the United nations to discuss the need for innovative partnerships

and financing models to deal with antibiotic resistance. One popular idea is de-linkage or finding a way to disconnect the costs of development from the sale of pills.

Some have suggested that large prizes of $1 billion or more be offered for the development of new drugs

which would then be sold for modest prices by other companies. The Infectious diseases Society of America (ISDA) has launched a 10 x 20 initiative

whose goal is to create global antibacterial drug research-and-development enterprise with the power in the short-term to develop 10 new safe and effective antibiotics by 2020.

Britain is offering a prize of £10 million called the Longitude Prize 2014 (after the prize once offered for an accurate way to determine the longitude of ships at sea) for a rapid test that would allow health professionals to identify bacteria quickly

and so administer only the right antibiotics at the right time. Newly arrived at Washington University in St louis Kinch is just beginning to think about the role the university might play in redefining its role.

In the past the hunting ground for new antibiotics was often the soil. Vancomycin for example was found in a soil sample from Borneo.

Antibiotics are not the only drug class heading for trouble--Kinch mentions that HIV/AIDS drugs are following a similar trajectory

--but they have become the poster child for the larger problem of drug discovery and development in part because they underpin every part of modern medical practice from surgery to cancer treatment and pretty much everything in between.


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Early detection and treatment typically with antibiotics and intravenous fluids is critical for survival. The Penn prediction tool dubbed the sepsis sniffer uses laboratory

two to threefold increase in orders for tests that could help identify the presence of sepsis 1. 5 to twofold increase in the administration of antibiotics


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and opened the door for drug discovery and transplantation therapy in diabetes, "Fuchs said. And Jose Oberholtzer, M d.,Associate professor of Surgery, Endocrinology and Diabetes,


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the study offers a blueprint for development of a drug specific to the task k


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if they need antibiotics...or just patience It's that time of the year where a perfect storm of fall allergies

and a prescription for antibiotics--despite evidence showing that in most cases, the medication won't help.

and less than 5 minutes later, physicians will be able to more confidently prescribe antibiotics for the estimated 10 percent of sinusitis sufferers who actually need them,

"The use of the test could translate into 18 million fewer people getting antibiotics that they don't need,

and a positive step towards addressing the major public health issue of antibiotic overuse.""Investors seem to agree.

"Research has shown that people with chronic sinusitis often have bacteria in their sinuses that have created biofilms--communities of bacteria with sticky protective covers that help them evade antibiotics and flourish unchecked.

not only help dramatically reduce the overuse of antibiotics in sinusitis, but could also be used to identify other types of pathogenic respiratory bacteria

"Das says the research also helps explain why viral infections appear to promote bacterial infections--a primary reason physicians will often"preemptively"prescribe antibiotics."

"Eighty to ninety percent of the time these symptoms will subside without any antibiotic needed,


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Kilmer and co-author Jesse Sussell examined one-year rearrest rates among those arrested for eligible offenses--such as theft, vandalism, drug offenses, assault and disorderly conduct--inside and outside the catchment area both before and after the Community Justice Center opened.


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which we now plan to use to screen the impact of drugs and antibodies that can shut it down,


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Dry powder inhaler formulation Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia remains a leading cause of morbidity and mortality, even in highly developed countries.

ciprofloxacin hydrochloride (CIP), an antibiotic commonly used to eliminate pathogenic bacteria, and beclomethasone dipropionate (BP), a corticosteroid commonly used to inhibit inflammatory responses.

The novelty of this formulation lies in the combination of the two drugs. Previous clinical trials have evaluated the efficacy, safety and tolerability of CIP on human patients.

and excellent antimicrobial activities,"explains Heng.""Our follow-up microbial assays show that a concentration as low as one microgram per milliliter is enough to inhibit three of the bacteria known to cause this type of pneumonia.""

Dry powder inhalers exhibit several advantages over traditional drug delivery methods, including improved formulation stability, enhanced delivery efficiency, excellent portability and ease of use.


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And many drugs work by targeting specific membrane proteins.""Currently, scientists only know the structure of a small handful of membrane proteins.

Our research paves the way to understand the structure of the thousands of different types of membrane proteins to allow the development of many new drugs


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#Universal Ebola drug target identified by researchers University of Utah biochemists have reported a new drug discovery tool against the Ebola virus.

This new tool can be used as a drug target in the discovery of anti-Ebola agents that are effective against all known strains and likely future strains.

and is currently screening for drugs against the target.)The Utah scientists designed peptide mimics of a highly conserved region in the Ebola protein that controls entry of the virus into the human host cell,

Importantly, the researchers were able to demonstrate this peptide target is suitable for use in high-throughput drug screens.

These kinds of screens allow rapid identification of potential new drugs from billions of possible candidates.

Current experimental drugs generally target only one of Ebola's five species."The current growing epidemic demonstrates the need for effective broad-range Ebola virus therapies,

Therefore, our target will enable the discovery of drugs with the potential to treat any future epidemic,

but a number of promising experimental drugs are being advanced aggressively to clinical trials to address the current crisis. Dr. Eckert notes,"

which are promising drug candidates. Unlike natural peptides, they are digested not by enzymes in the blood.


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and may be key to developing new drugs and therapies. Specifically principal investigator Albert R. La Spada MD Phd professor of cellular and molecular medicine chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic


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because not only have shown we this particular part of the protein is essential for necroptosis we also have a starting point in a drug discovery program.

Dr Murphy said institute scientists would now embark on a collaborative project with Catalyst Therapeutics to develop a potent new drug based on the small molecule identified in the study.


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The optimal drug therapies we have today often aren't enough to manage this disease for some patients

Drug and device therapies that are currently available for heart failure improve that same quality of life score by only five or 10 points.

and antibiotic therapy could reduce that risk in future studies. There were no hospitalizations among the participants for stroke thrombosis sepsis or bleeding


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"Hijacking the hijacker"A tempting premise is to use this same machinery to introduce drugs or genes into the nervous system,"Dr. Perlson added.


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and limit the spread of the virus. A drug of this type affects the physical properties of the virus's DNA

which means that the drug can resist the virus's mutations said Alex Evilevitch. The second study that Evilevitch and his colleagues have published recently is about bacteriophages


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and demonstrated how the MFICS can size droplets precisely a useful function for drug delivery or studying microreactor chambers.


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If you want to use your boat sooner clean all surfaces with hot (over 104 degrees F.)water a high-pressure hose or a disinfectant like a household bleach solution.


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and only one therapy has been approved by the Food and Drug Administration. While most of these vaccines are created with dendritic cells,


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In 2014, Cowan identified two drugs with the potential to convert stem cells that make white fat into those that would make brown. his latest study gives us new tools and targets to use in the battle against obesity


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-or right-handed form may have a multitude of practical applications, potentially leading to new and improved drugs, diagnosis methods, and pesticides.

The breakthrough could be important in developing effective molecules for use in a wide range of industries everything from the development of safer new drugs and disease diagnosis to less toxic pesticides.

for instance with chiral drugs. Presently, more than 50 per cent of all drugs produced are active in only one of their two handed forms.

The chemistry of life Dr Ivan Powis, Professor of Chemical Physics in the University School of Chemistry, who led the research,

for instance the well-known malformation of the limbs of infants of pregnant women taking the Thalidomide drug to relieve morning sickness that occurred around 1960.

In addition to the development of effective new drugs and diagnosis methods for diseases including cancer, it could potentially lead to new reenpesticides using pheromones tailored specifically to attract pollinators


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or even stop their current HIV drug regimen and clear the virus from the body altogether,

Certain drugs help suppress the virus, but since the human immune system can clear the virus from the body,

people with HIV have the virus for life. espite increased scientific understanding of HIV and better prevention and treatment with available drugs, a majority of the 35 million people living with HIV,


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#Yale Researchers Successfully Treat Eczema with Rheumatoid arthritis Drug A team of scientists at Yale university used a rheumatoid arthritis drug to successfully treated patients with moderate to severe eczema.

The same rheumatoid arthritis drug (tofacitinib citrate) has shown recently to reverse two other disfiguring skin conditions, vitiligo and alopecia areata.

Based on current scientific models of eczema biology, assistant professor of dermatology Dr. Brett King. hypothesized that a drug approved for rheumatoid arthritis,

In the new study, King and his colleagues report that treatment with the drug led to dramatic improvement in six patients with moderate to severe eczema who had tried previously conventional therapies without success. During treatment all six


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They initially sought to develop nanoparticles that could be used to deliver drugs to cancer cells. Brandl had synthesized previously polymers that could be cleaved apart by exposure to UV LIGHT.

But he and Bertrand came to question their suitability for drug delivery, since UV LIGHT can be damaging to tissue and cells,

and approved by the Food and Drug Administration as a food additive, and polylactic acid, a biodegradable plastic used in compostable cups and glassware.

The study also suggests the broader potential for adapting nanoscale drug-delivery techniques developed for use in environmental remediation. hat we can apply some of the highly sophisticated,


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and other disciplines also tested the response of tumor cells with specific mutations to anticancer drugs.

in addition to loss of NF1, multiple factors need to be tested to predict the response to the drugs. t opens the door to more research,


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Clinics have to track their drugs, generate tedious reports to get new supplies and deliver those reports to central facilities.

the clinic wouldn get the drugs it needed to treat its patients. The 3g technology has allowed clinics to computerize much of their administrative work,


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their treatment options are limited to antibiotics, blood transfusions, and fluid supplements to deal with the symptoms of the disease.

All of these drugs are being developed under the FDA nimal rule, which requires extensive efficacy data in animal models,

Since many of these drugs have passed already human safety testing they could be on the market before the next nuclear catastrophe strikes p


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Doctors prescribe antidepressants in the Beehive state at nearly twice the average rate in the U s. Speculation as to


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its Scanaflow device is an at home urine-testing apparatus that can test for drugs or even a possible pregnancy. lot more healthcare is going to happen in the home in the future,


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a first that could allow researchers to test drugs on working muscle without damaging a live host.

and responds to drugs just like regular human muscle as replacements for lost musculature, which suggests the samples are still too small to be useful.

and it looks like it will be a real boon for researchers trying to figure out the effects of various diseases and drugs on the body.


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Not sure if that pill youe taking is Aspirin or Ibuprofen? Worried that your local pharmacy is slipping you some sort of generic drug instead of the real thing?

Well a new handheld scanning device called SCIO could ensure that the stuff youe putting in your body is actually stuff you want to ingest.

but powerful scanner that can be pointed at a thing like a pill or a liquid or even a piece of fruit and tell you exactly what it made of.

and drugs they eat. Using near infrared spectroscopy the device connects with a mobile app


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The Regulatory Pathwaythe U s. Food & Drug Administration (FDA) has created three categories of MMAS: Of more than 43000 health-related apps available by 2013 only 103 were regulated FDA Tighe says.


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The Regulatory Pathwaythe U s. Food & Drug Administration (FDA) has created three categories of MMAS: Of more than 43000 health-related apps available by 2013 only 103 were regulated FDA Tighe says.


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That because just a month earlier, in November 2013, the Food and Drug Administration had cracked down on 23andme.

or take a drug overdose. Critics of the decision said it had more to do with questions about

or lower, their risk for drug reactions, common diseases, or personality traits such as a lack of empathy.

and avoid drugs like Novocain. think that how people should be using thiss a conversation-starter with medical professionals,


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Ello on the other hand positions itself as an antidote to that: it doesn t include any ads and one of several manifestos posted on the site says that those behind Ello dislike ads more than almost anyone else out there.


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#Gene-Silencing Drugs Finally Show Promise The disease starts with a feeling of increased clumsiness.

because it suggested a way to shut down the production of any protein in the body including those connected with diseases that couldn't be touched with ordinary drugs.

Never mind that no one knew how to make a drug that could trigger RNAI. In fact that challenge would bedevil the researchers for the better part of a decade.

But now Alnylam is testing a drug to treat FAP in advanced human trials. It s the last hurdle before the company will seek regulatory approval to put the drug on the market.

Although it s too early to tell how well the drug will alleviate symptoms it s doing

what the researchers hoped it would: it can decrease the production of the protein that causes FAP by more than 80 percent.

Alnylam has more than 11 drugs including ones for hemophilia Hepatitis b and even high cholesterol in its development pipeline and has three in human trials progress that led the pharmaceutical company Sanofi to make a $700 million investment in the company last winter.

All told there are about 15 RNAI-based drugs in clinical trials from several research groups and companies.

The early mechanisms were too toxic at the doses required to be used as drugs. As a result delivering RNA through the bloodstream like a conventional drug seemed a far-off prospect.

The company tried a shortcut of injecting chemically modified RNA directly into diseased tissue for example into the retina to treat eye diseases.

because it didn t perform as well as up-and-coming drugs from other companies. By 2010 some of the major drug companies that were working with and investing in Alnylam lost patience.

Better nanoparticles improved the potency of a drug a hundredfold and its safety by about five times clearing the way for clinical trials for FAP a crucial event that kept the company alive.

This approach allows for the drug to be administered with a simple injection that patients could give themselves at home.

In addition to being easier to administer the new sugar-based drugs are potentially cheaper to make.

For all of their benefits the drug delivery mechanisms Alnylam uses have one flaw they re effective only for delivering drugs to liver cells.

but if it maintains its momentum the drugs currently in clinical trials could represent just a small portion of the benefits of the discovery of RNAI i


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