Showing posts with label Drugs. Show all posts
Showing posts with label Drugs. Show all posts

Tuesday, 30 July 2013

Restless legs syndrome: Study raises hope for better drugs

Editor's Choice
Main Category: Restless Legs Syndrome
Also Included In: Neurology / Neuroscience
Article Date: 30 Jul 2013 - 8:00 PDT Current ratings for:
Restless legs syndrome: Study raises hope for better drugs
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John Hopkins researchers may have discovered why insomnia persists in patients with restless legs syndrome (RLS), despite successful treatment of the condition. 

People with restless legs syndrome, sometimes called "jimmy legs," have an uncontrollable urge to move their legs. The condition varies in severity and can be painful, distressing and interrupt daily activities as well as disturb sleep. 

In spite of effective drugs to relieve RLS, studies have shown that they do not improve sleep outcomes and only treat the restless legs. 

A research team led by Dr. Richard Allen, associate professor of neurology at John Hopkins University School of Medicine, has looked into solving the sleep anomaly, using MRI to image the brain in a group of 28 RLS patients and 20 non-RLS patients. 

Glutamate, the neurotransmitter involved in arousal, was found in abnormally high levels in the RLS group. The higher the level of glutamate recorded in the brain of those with RLS, the worse the patient's sleep. 

The research team recorded MRI images and glutamate activity in the thalamus - the part of the brain involved with the regulation of consciousness, sleep and alertness. 

RLS patients included in the study had severe symptoms: 

On six or seven nights a weekPersisting for at least six monthsWith an average of at least 20 involuntary movements a night.

The second stage of the experiment involved a two-day sleep study. RLS patients were reported to have received 5.5 hours sleep on average. The researchers identified a direct link in this group between glutamate levels in the thalamus and the number of hours of sleep. There was no such association in the non-RLS control group. 

Dr. Richard Allen is hopeful that the team may have discovered the reason why restless legs syndrome also affects sleep. He says:

"We may have solved the mystery of why getting rid of patients' urge to move their legs doesn't improve their sleep.

We may have been looking at the wrong thing all along, or we may find that both dopamine and glutamate pathways play a role in RLS."

The results of the study could lead to developments in the way RLS is treated, potentially helping to eradicate sleepless nights for people with restless legs syndrome. 

Dopamine-related drugs do work for many people with RLS, yet some lose benefit and require ever-higher doses. If the dose is too high, medication can aggravate symptoms to a state worse than that prior to treatment.

Dr. Richard Allen points out that despite drugs already being available that can reduce glutamate levels in the brain, such as the anticonvulsive drug gabapentin enacarbil (Horizant), they have not been given as a first-line treatment for RLS patients.

Dr. Allen adds that as more is understood about the neurobiology, his findings could apply to some forms of insomnia as well as restless legs syndrome.

Dr. Richard Allen says:

"It's exciting to see something totally new in the field - something that really makes sense for the biology of arousal and sleep."

Written by Sally Burr

See Sally's blog


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our restless legs syndrome section for the latest news on this subject.

Allen RP, Barker PB, Horská A and Earley CJ, Neurology, 2013 vol. 80 no. 22, pp2028-2034. Abstract/summary

The study was funded in part by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (R01 NS075184 and NS044862), the National Institute on Aging (P10-AG21190) and the National Center for Research Resources (M01RR02719).

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Technique to create better anti-cancer agents, arthritis drugs, and more

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Medical Devices / Diagnostics;  Arthritis / Rheumatology
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
Technique to create better anti-cancer agents, arthritis drugs, and more
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Many drugs such as agents for cancer or autoimmune diseases have nasty side effects because while they kill disease-causing cells, they also affect healthy cells. Now a new study has demonstrated a technique for developing more targeted drugs, by using molecular "robots" to hone in on more specific populations of cells.

"This is a proof of concept study using human cells," said Sergei Rudchenko, Ph.D., director of flow cytometry at Hospital for Special Surgery (HSS) in New York City and a senior author of the study. "The next step is to conduct tests in a mouse model of leukemia." The study, a collaboration between researchers from HSS and Columbia University, is in Advance Online Publication on the website of Nature Nanotechnology.

All cells have many receptors on their cell surface. When antibodies or drugs bind to a receptor, a cell is triggered to perform a certain function or behave in a certain manner. Drugs can target disease-causing cells by binding to a receptor, but in some cases, disease-causing cells do not have unique receptors and therefore drugs also bind to healthy cells and cause "off-target" side effects.

Rituximab (Rituxan, Genentech), for example, is used to treat rheumatoid arthritis, non-Hodgkin's lymphoma and chronic lymphocytic leukemia by docking on CD20 receptors of aberrant cells that are causing the diseases. However, certain immune cells also have CD20 receptors and thus the drug can interfere with a person's ability to mount a fight against infection.

In the new study, scientists have designed molecular robots that can identify multiple receptors on cell surfaces, thereby effectively labeling more specific subpopulations of cells. The molecular robots, called molecular automata, are composed of a mixture of antibodies and short strands of DNA. These short DNA strands, otherwise called oligonucleotides, can be manufactured by researchers in a laboratory with any user-specified sequence.

The researchers conducted their experiments using white blood cells. All white blood cells have CD45 receptors, but only subsets have other receptors such as CD20, CD3, and CD8. In one experiment, HSS researchers created three different molecular robots. Each one had an antibody component of either CD45, CD3 or CD8 and a DNA component. The DNA components of the robots were created to have a high affinity to the DNA components of another robot. DNA can be thought of as a double stranded helix that contains two strands of coded letters, and certain strands have a higher affinity to particular strands than others.

The researchers mixed human blood from healthy donors with their molecular robots. When a molecular robot carrying a CD45 antibody latched on to a CD45 receptor of a cell and a molecular robot carrying a CD3 antibody latched on to a different welcoming receptor of the same cell, the close proximity of the DNA strands from the two robots triggered a cascade reaction, where certain strands were ripped apart and more complementary strands joined together. The result was a unique, single strand of DNA that was displayed only on a cell that had these two receptors.

The addition of a molecular robot carrying a CD8 antibody docking on a cell that expressed CD45, CD3 and CD8 caused this strand to grow. The researchers also showed that the strand could be programmed to fluoresce when exposed to a solution. The robots can essentially label a subpopulation of cells allowing for more targeted therapy. The researchers say the use of increasing numbers of molecular robots will allow researchers to zero in on more and more specific subsets of cell populations. In computer programming language, the molecular robots are performing what is known as an "if yes, then proceed to X function."

"The automata trigger the growth of more strongly complementary oligonucleotides. The reactions occur fast. In about 15 minutes, we can label cells," said Maria Rudchenko, M.S., the first author of the paper and a research associate at Hospital for Special Surgery. In terms of clinical applications, researchers could either label cells that they want to target or cells they want to avoid.

"This is a proof of concept study that it works in human whole blood," said Dr. Rudchenko. "The next step is to test it in animals."

If molecular robots work in studies with mice and eventually human clinical trials, the researches say there are a wide range of possible clinical applications. For example, cancer patients could benefit from more targeted chemotherapeutics. Drugs for autoimmune diseases could be more specifically tailored to impact disease-causing autoimmune cells and not the immune cells that people need to fight infection.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our lymphoma / leukemia / myeloma section for the latest news on this subject.

The study was funded, in part, by the National Institutes of Health, National Science Foundation, and the Lymphoma and Leukemia Foundation.

Other researchers involved with the study are Alesia Dechkovskaia from Hospital for Special Surgery, and Steven Taylor, Ph.D., Payal Pallavi, B.A., Safana Khan, Vincent Butler, M.D., and Milan Stojanovic, Ph.D., from Columbia University. Dr. Stojanovich is also a senior author.

Hospital for Special Surgery

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Sunday, 28 July 2013

Discovery of new target for breast cancer drugs

Main Category: Breast Cancer
Article Date: 24 Jul 2013 - 0:00 PDT
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Scientists have identified higher levels of a receptor protein found on the surface of human breast tumour cells that may serve as a new drug target for the treatment of breast cancer. The results, which are published in EMBO Molecular Medicine, show that elevated levels of the protein Ret, which is short for "Rearranged during transfection", are associated with a lower likelihood of survival for breast cancer patients in the years following surgery to remove tumours and cancerous tissue.

"Our findings suggest that Ret kinase might be an attractive and novel alternative therapeutic target in selected groups of breast cancer patients," remarked Nancy Hynes, Professor at the Friedrich Miescher Institute for Biomedical Re-search and the University of Basel, Switzerland. "Initial experiments in mice that serve as model organisms for the study of breast cancer have revealed that specific inhibitors significantly block the spread of cancer and decrease the number of metastatic tumours found in the lungs."

The scientists examined tumour tissue microarrays of more than 100 breast cancer patients who had undergone surgery to remove their tumours. Antibodies were used to detect the levels of Ret in the samples. In other experiments, four different cancer cell lines were used and injected into mice to study the effects of Ret inhibitors on the progress and spread of the cancer.

"Our findings demonstrate that blocking Ret kinase not only decreases the growth of tumours but also impacts the potential of the cancer to spread throughout the body," Hynes said.

Targeting receptor tyrosine kinase enzymes with antibodies or small molecular inhibitors is a clinically validated approach for cancer therapy. However, only a subset of patients are eligible for these types of treatments which makes it essential to discover additional inhibitors that could be useful in breast cancer therapy.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our breast cancer section for the latest news on this subject.

Dr. Albana Gattelli was supported by grant KG101234 from Susan G. Komen for the Cure®

"Ret inhibition decreases growth and metastatic potential of estrogen receptor positive breast cancer cells", Albana Gattelli, Ivan Nalvarte, Anne Boulay, Tim C. Roloff, Martin Schreiber, Neil Carragher, Kenneth K. Macleod, Michaela Schlederer, Susanne Lienhard, Lukas Kenner, Maria I. Torres-Arzayus and Nancy E. Hynes, doi: 10.1002/emmm.201302625

European Molecular Biology Organization

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Treating people who use drugs is the first step towards eliminating hepatitis C - international guidelines for treatment released today

Main Category: Liver Disease / Hepatitis
Also Included In: Alcohol / Addiction / Illegal Drugs
Article Date: 25 Jul 2013 - 1:00 PDT Current ratings for:
Treating people who use drugs is the first step towards eliminating hepatitis C - international guidelines for treatment released today
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The burden of liver disease could be dramatically reduced by increasing treatment for hepatitis C infection among people who inject drugs, suggest new recommendations developed by researchers from the Kirby Institute at UNSW, in collaboration with colleagues from the International Network on Hepatitis Care in Substance Users (INHSU).

In Australia, 226,000 people are living with chronic hepatitis C and over 10,000 new cases are reported every year. Hepatitis C can lead to serious liver complications such as liver failure or cancer, which are associated with considerable costs to the health care system. Although almost 80 per cent of all infections occur among people who inject drugs, only one per cent of these people currently receive treatment.

"Treatment for hepatitis C infection among people who inject drugs remains unacceptably low," said Dr Jason Grebely, Senior Lecturer at the Kirby Institute, UNSW, and co-lead author of the recommendations. "Clinicians have been hesitant to recommend treatment in this population because of a lack of understanding about how lifestyle factors may impede successful treatment."

But research supporting the first set of international recommendations ever released for treating hepatitis C in people who inject drugs has shown that treatment can be very successful when barriers are addressed within a supportive environment.

"Reducing the significant burden of liver disease related to hepatitis C in Australia and internationally will require improved assessment and treatment of the population most affected: people who currently inject drugs and those who have injected drugs in the past," says Philip Bruggmann, President of INHSU. "By providing appropriate care to this group, we can reduce the burden of hepatitis C-related liver disease in this vulnerable population and slow the spread of this world-wide epidemic. These new recommendations serve as a first step towards elimination of hepatitis C."

The global recommendations are published online today in the journal Clinical Infectious Diseases ahead of World Hepatitis Day on July 28. They are part of a supplement entitled "Prevention and Management of Hepatitis C Virus Infection Among People Who Inject Drugs: Moving the Agenda Forward", developed in collaboration with INHSU.

Additional Stakeholder Comments:

"These are exceptionally positive and welcome findings. Following the listing of new hep C treatments for subsidy by the Australian Government in April, almost all people in Australia living with hepatitis C in Australia can enjoy cure rates of around 75 to 80 per cent. This new evidence shows us that people who have been least able to access treatment in the past, can and should be able to benefit from these new treatment advances."

Stuart Loveday
CEO of Hepatitis NSW

"This report is most welcomed. It finally provides the much needed endorsement that peer support requires to validate it as an efficacious treatment modality. That combined with the recognition that people who continue to inject or use drugs can access treatment will mean that more people will be able to access treatment. For too long those most affected by hepatitis C have been on the periphery, this report puts them where they belong - front and centre."

Nicky Bath
CEO of the NSW Users and AIDS Association

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Saturday, 27 July 2013

Common blood pressure drugs may slow dementia decline

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Academic Journal
Main Category: Alzheimer's / Dementia
Also Included In: Cardiovascular / Cardiology
Article Date: 26 Jul 2013 - 8:00 PDT Current ratings for:
Common blood pressure drugs may slow dementia decline
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A class of drug used to lower blood pressure could potentially slow the rate of cognitive decline in dementia and even boost brain power, according to a study published by BMJ Open.

Researchers from Ireland analyzed the cognitive decline and brain power of 361 patients with an average age of 77. All had been diagnosed with either Alzheimer's disease, vascular dementia, or a mixture of both.

Of these patients, 85 were already using the blood pressure-lowering (antihypertensive) drugs known as ACE inhibitors (angiotensin-converting enzyme inhibitors). This is a commonly used class of antihypertensive drug. Thirty of the patients who were newly prescribed ACE inhibitors during the first six months of treatment were also analyzed for their brain power activity.

Between the years 1999 and 2010, the researchers used the Standardized Mini Mental State Examination (SMMSE) or the Quick Mild Cognitive Impairment (Qmci) to test the cognitive decline of each patient. This was done on two separate occasions, six months apart.

The patients who were taking ACE inhibitors had slower rates of cognitive decline in the study compared with patients who were not taking the drugs.

The study also revealed that in patients who had been newly prescribed the ACE inhibitors over the six-month period, their brain power improved in comparison with both those already taking them and those not taking them at all.

However, the study authors add that this could be due to the newly prescribed patients having better control over their medication regimen, or due to better blood pressure control or improved blood flow to the brain.

The researchers say:

"This [study] supports the growing body of evidence for the use of ACE inhibitors and other [blood pressure-lowering] agents in the management of dementia.

Although the differences were small and of uncertain clinical significance, if sustained over years, the compounding effects may well have significant clinical benefits."

The researchers warn, however, that previous research has indicated that ACE inhibitors may be harmful in some cases, so if future benefit of the drugs in dementia is proven, it may be limited to certain groups of patient.

The study authors call for further research and a controlled trial to confirm their findings. They say:

"If these data can be reproduced in a randomized trial of sufficient length, incorporating appropriate outcome measures, such as an amyloid positron emission tomography (PET), then these agents are likely to have significant benefits in delaying or even preventing dementia."

Written by Honor Whiteman


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our alzheimer's / dementia section for the latest news on this subject. "Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia," BMJ Open, 22 July 2013: e002881. DOI: 10.1136/bmjopen-2013-002881 Please use one of the following formats to cite this article in your essay, paper or report:

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Thursday, 25 July 2013

Potential for drugs to 'switch off' high blood pressure

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Main Category: Hypertension
Also Included In: Cardiovascular / Cardiology
Article Date: 24 Jul 2013 - 2:00 PDT Current ratings for:
Potential for drugs to 'switch off' high blood pressure
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US researchers have designed new molecules that could be used as a starting point for developing drugs that "switch off" high blood pressure in the body.

The scientists first studied natural molecules that the body uses to control blood pressure, identified the parts that are actively involved in switching off the signaling that leads to hypertension, and then designed "analogs" of the natural compounds to do the same.

The work, which focuses on one natural compound in particular, is reported in the July 17th online issue of Bioorganic & Medicinal Chemistry.

Senior author Daniel O'Connor, a professor at the University of California San Diego (UCSD) School of Medicine, says in a statement:

"Our results suggest that analogs can be designed to match the action of catestatin, which the body uses to regulate blood pressure.

Those designer analogs could ultimately be used for treatment of hypertension or autonomic dysfunction."

Catestatin is a natural hormone that acts as the gatekeeper for the secretion of catecholamines - hormones that are released into the bloodstream during times of physical or emotional stress.

A drug that mimics this action would thus help control the hormones that regulate blood pressure.

In the US, around a third of adults - over 70 million people - have high blood pressure, and according to a 2012 report from the Centers for Disease Control and Prevention (CDC), over half do not have their hypertension under control.

If not treated, high blood pressure damages blood vessels and raises the risk of kidney failure, heart attack and stroke.

Yet despite it being a common and sometimes deadly condition, current treatments for high blood pressure only partially control it, and most have serious side effects.

To regulate blood pressure, catestatin binds to nicotinic acetylcholine receptors found in the nervous system.

In earlier studies, Daniel O'Connor and colleagues had already figured out which parts of catestatin bind to the receptor, rather like mapping how the various ridges on a key help open a lock.

In this latest study they studied these "ridges" and developed a three-dimensional chemical model of the most important binding centers.

They then used this 3D model to search a library of 250,000 compound structures for molecules with a similar "fingerprint," tested them on live cells and uncovered some that successfully lowered hypertension.

In further experiments using live mice with high blood pressure, they found that one compound in particular, TKO-10-18, had the same antihypertensive effect as catestatin.

Lead author Igor Tsigelny, a research scientist with the UCSD's San Diego Supercomputer Center (SDSC), says:

"This approach demonstrates the effectiveness of rational design of novel drug candidates."

The team says with further refinement, the model should lead to a new class of drugs to treat high blood pressure.

Written by Catharine Paddock PhD


Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today Visit our hypertension section for the latest news on this subject. "Development of a pharmacophore model for the catecholamine release-inhibitory peptide catestatin: Virtual screening and functional testing identify novel small molecule therapeutics of hypertension"; Igor F. Tsigelny, Valentina L. Kouznetsova, Nilima Biswas, Sushil K. Mahata, Daniel T. O'Connor; Bioorganic & Medicinal Chemistry Available online 17 July 2013; DOI:10.1016/j.bmc.2013.07.008; Link to Abstract. Additional source: UCSD News. Please use one of the following formats to cite this article in your essay, paper or report:

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Sunday, 14 July 2013

Health Minister reveals 110 drugs deaths in Ulster

News Letter Sunday 14th July, 2013

Around 110 people died in Northern Ireland last year as a consequence of drugs misuse, the Health Minister has warned. Edwin Poots reiterated the dangers as police continued to investigate a recent spate of eight sudden deaths in the region linked to illegal substances.Two of the deaths have been linked to a lethal batch of fake ecstasy tablets, so-called "Green Rolexes".The type of pills, which are embossed with a crown, have also been linked to seven deaths of young people in Scotland in recent months.The other six sudden deaths being investigated by police in Northern Ireland potentially i...

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Friday, 12 July 2013

Novel Nanoparticle Developed To Deliver Powerful RNA Interference Drugs

Main Category: Genetics
Article Date: 11 Jul 2013 - 1:00 PDT Current ratings for:
Novel Nanoparticle Developed To Deliver Powerful RNA Interference Drugs
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Silencing genes that have malfunctioned is an important approach for treating diseases such as cancer and heart disease. One effective approach is to deliver drugs made from small molecules of ribonucleic acid, or RNA, which are used to inhibit gene expression. The drugs, in essence, mimic a natural process called RNA interference.

In a new paper appearing online in the journal, ACS Medicinal Chemistry Letters, researchers at Sanford-Burnham Medical Research Institute have developed nanoparticles that appear to solve a big challenge in delivering the RNA molecules, called small interfering RNA, or siRNA, to the cells where they are needed. By synthesizing a nanoparticle that releases its siRNA cargo only after it enters targeted cells, Dr. Tariq M. Rana and colleagues showed in mice that they could deliver drugs that silenced the genes they wanted.

"Our study describes a strategy to reduce toxic effects of nanoparticles, and deliver a cargo to its target," said Dr. Rana, whose paper, "In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)," also included contributions from researchers at the University of Massachusetts Medical School and the University of California at San Diego. "We've found a way to release the siRNA compounds, so it can be more effective where it's needed," Dr. Rana said.

In their experiment, the team synthesized what they call interfering nanoparticles, or iNOPs, made from repetitively branched molecules of a small natural polymer called poly-L-lysine. The iNOPs were specially designed with positively charged residues connected by disulfide bonds and these iNOPS assemble into a complex with negatively charged siRNA molecules. It's the bonds that ensure that the siRNA molecules remain with the nanoparticle, named iNOP-7DS. However, once inside targeted cells, a naturally occurring and abundant antioxidant called glutathione breaks the bond, releasing the siRNA molecules. In their experiment, Dr. Rana and colleagues showed in the lab that iNOP-7DS is reducible - that is, the disulfide bonds holding the siRNA molecules can be broken.

They next showed that iNOP-7DS can be delivered effectively inside cultured murine liver cells, where the siRNA molecules silenced a gene called ApoB. This gene has been notoriously difficult to regulate in liver cells with small molecule drugs; high levels of the protein that ApoB encodes can lead to plaques that cause vascular disease.

Dr. Rana's lab further showed in tests that their nanoparticle remained stable in serum, suggesting that it is not degraded in the bloodstream. Finally, the researchers showed in tests with mice that their nanoparticle iNOP-7DS can be delivered effectively to the liver, spleen, and lung; and it suppressed the level of messenger RNA involved in the expression of the ApoB gene. In their in vivo experiment, they found that extremely small doses of siRNA were effective.

The next step, Dr. Rana said, is to increase the efficacy of iNOP-7DS in other in vivo experiments. "We would like to target not only ApoB, but cancer causing genes as well and in other tissues. That is the next goal." By marshaling the naturally occurring phenomenon of RNA interference, scientists are developing new ways to silence errant gene expression involved in illnesses. The nanoparticles developed by Dr. Rana and colleagues offer a potential new strategy for delivering this powerful therapeutic approach.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Thursday, 11 July 2013

Novel Nanoparticle Developed To Deliver Powerful RNA Interference Drugs

Main Category: Genetics
Article Date: 11 Jul 2013 - 1:00 PDT Current ratings for:
Novel Nanoparticle Developed To Deliver Powerful RNA Interference Drugs
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Silencing genes that have malfunctioned is an important approach for treating diseases such as cancer and heart disease. One effective approach is to deliver drugs made from small molecules of ribonucleic acid, or RNA, which are used to inhibit gene expression. The drugs, in essence, mimic a natural process called RNA interference.

In a new paper appearing online in the journal, ACS Medicinal Chemistry Letters, researchers at Sanford-Burnham Medical Research Institute have developed nanoparticles that appear to solve a big challenge in delivering the RNA molecules, called small interfering RNA, or siRNA, to the cells where they are needed. By synthesizing a nanoparticle that releases its siRNA cargo only after it enters targeted cells, Dr. Tariq M. Rana and colleagues showed in mice that they could deliver drugs that silenced the genes they wanted.

"Our study describes a strategy to reduce toxic effects of nanoparticles, and deliver a cargo to its target," said Dr. Rana, whose paper, "In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)," also included contributions from researchers at the University of Massachusetts Medical School and the University of California at San Diego. "We've found a way to release the siRNA compounds, so it can be more effective where it's needed," Dr. Rana said.

In their experiment, the team synthesized what they call interfering nanoparticles, or iNOPs, made from repetitively branched molecules of a small natural polymer called poly-L-lysine. The iNOPs were specially designed with positively charged residues connected by disulfide bonds and these iNOPS assemble into a complex with negatively charged siRNA molecules. It's the bonds that ensure that the siRNA molecules remain with the nanoparticle, named iNOP-7DS. However, once inside targeted cells, a naturally occurring and abundant antioxidant called glutathione breaks the bond, releasing the siRNA molecules. In their experiment, Dr. Rana and colleagues showed in the lab that iNOP-7DS is reducible - that is, the disulfide bonds holding the siRNA molecules can be broken.

They next showed that iNOP-7DS can be delivered effectively inside cultured murine liver cells, where the siRNA molecules silenced a gene called ApoB. This gene has been notoriously difficult to regulate in liver cells with small molecule drugs; high levels of the protein that ApoB encodes can lead to plaques that cause vascular disease.

Dr. Rana's lab further showed in tests that their nanoparticle remained stable in serum, suggesting that it is not degraded in the bloodstream. Finally, the researchers showed in tests with mice that their nanoparticle iNOP-7DS can be delivered effectively to the liver, spleen, and lung; and it suppressed the level of messenger RNA involved in the expression of the ApoB gene. In their in vivo experiment, they found that extremely small doses of siRNA were effective.

The next step, Dr. Rana said, is to increase the efficacy of iNOP-7DS in other in vivo experiments. "We would like to target not only ApoB, but cancer causing genes as well and in other tissues. That is the next goal." By marshaling the naturally occurring phenomenon of RNA interference, scientists are developing new ways to silence errant gene expression involved in illnesses. The nanoparticles developed by Dr. Rana and colleagues offer a potential new strategy for delivering this powerful therapeutic approach.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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