This blog is all about current FDA approved drugs to treat the hepatitis C virus (HCV) with a focus on treating HCV according to genotype, using information extracted from peer-reviewed journals, liver meetings/conferences, and interactive learning activities.
Risk Of Developing Liver Cancer After HCV Treatment
Perceptions of Hep C treatment in opiate substitution treatment
The latest issue of the Journal of Viral Hepatitis investigates perceptions of clients and health professionals and hepatitis C treatment in opiate substitution treatment. Uptake of treatment for hepatitis C virus infection is very low particularly among people who have injected drugs.
Opiate substitution treatment programs, with a high prevalence of people living with hepatitis C, have been a site of growing interest in the delivery of hepatitis C treatment. There has been no exploration of OST clients’ and health professionals’ perceptions of the barriers and facilitators to uptake and delivery of Hepatitis C treatment in OST clinics from personal and organizational perspectives.
Organizational culture as barriers to Hepatitis C treatment delivery Journal of Viral Hepatitis
Dr Treloar and colleagues from Australia completed a qualitative study involving interviews with 27 opiate substitution treatment clients in New South Wales, and a focus group and interviews with 22 Australian opiate substitution treatment health professionals. Clients and health professionals viewed hepatitis C treatment in opiate substitution treatment as a ‘one-stop-shop’ model which could increase access to and uptake of treatment and build on existing relationships of trust between opiate substitution treatment client and health professional.
The research team noted elements of the organizational culture as barriers to Hepatitis C treatment delivery.
The team found that confidentiality, lack of discussion of hepatitis C treatment and that hepatitis C treatment was not perceived by clinicians as a legitimate activity of opiate substitution treatment clinics.
Opiate substitution treatment client participants also reported a number of personal barriers to engaging with Hepatitis C treatment including family responsibilities, unstable housing, comorbidities and perceptions of the unsatisfactory level of treatment efficacy. Dr Treloar's team concludes, "These findings emphasize the need for future research and delivery of services which addresses the complexity of care and treatment for people in marginalized social circumstances."
Hello Folks, today Medgadget added a video (see below) presentation on "Microsulis microwave ablation (MWA) system" which is used to destroy liver tumors by heat generated microwave energy. The device is beneficial when liver tumors can not be removed surgically. The advantages of MWA over RFA (Radiofrequency Ablation) are highlighted below
Microwave ablation (MWA) is used to treat inoperable liver tumors.
These include hepatocellular carcinoma or (primary liver cancer) that originates in the liver.
HCC (hepatocellular carcinoma) is a disease associated with cirrhosis and hepatitis B and C .
What Is Secondary Liver Cancer ?
Metastatic or secondary liver cancer results through the spread of cancer from another organ in the body, Because the liver has two blood supplies and a ready store of growth factors, it is a fertile site for liver metastases, liver tumors originating elsewhere in the body. Abdominal cancers, and especially colorectal cancer, frequently metastasize to the liver.
What Is Microwave ablation (MWA) ?
A new technology, microwave ablation (MWA), destroys liver tumors using heat generated by microwave energy. With microwave ablation, the surgeon inserts a small laparoscopic port or open incision to access the tumor. A CT scan or ultrasonic guidance is used to pinpoint the exact location of the tumor. A thin antenna, which emits microwaves, is then inserted into the tumor. The probe produces intense heat that ablates (destroys) tumor tissue, often within 10 minutes.
,What Are The Advantages Over Traditional RFA= Radiofrequency Ablation ?
"According to the American Cancer Society, more than 450,000 Americans suffer from lung and liver cancer annually. Historically treatment options for these types of cancer have included one or a combination of treatments including surgical removal of the cancer, chemotherapy, radiofrequency ablation (RFA), or radiation therapy. Ablative therapies which aim to destroy tumors in-situ are limited by the number and size of the tumors that can be targeted and so it’s not an option in many cases due to the limited performance of existing RFA and microwave systems. However the Acculis Accu2i pMTA system is the first high power 2.45 GHz system that enables larger and faster ablations to be performed. This means that ablative therapy will now be available as an option for many more patients".
Microwave ablation has a number advantages when compared to traditional RFA, which is a standard method for ablating liver tumors
These include:
Speed - Microwave ablation (MWA) is faster than RFA, destroying tumors more efficiently, and reducing the time patients remain under general anesthesia.
Simultaneous Tumor Ablation - With MWA, surgeons can ablate multiple liver tumors at the same time.
Larger Tumor Size - MWA can ablate larger tumors than are possible with RFA.
, What Is Radiofrequency Ablation (RFA) Therapy ?
How is RFA done and how does it work? In RFA, heat is generated locally by a high frequency, alternating current that flows from the electrodes. A probe is inserted into the center of the tumor and the non-insulated electrodes, which are shaped like prongs, are projected into the tumor. The local heat that is generated melts the tissue (coagulative necrosis) that is adjacent to the probe. The probe is left in place for about 10 to 15 minutes.
“Increasing numbers of clinicians around the world are adopting the radically improved performance and ease of use of the Acculis system, moving away from older radiofrequency ablation systems. The groundbreaking performance of the device reflects the extensive testing the device has undergone to the highest standards around the world.”
The Accu2i pMTA is the most powerful tumour ablation system currently available, combining extreme ease of use with the widest range of clinical applications. The device is a single high power high frequency 2.45GHz microwave needle that can address tumours over 5cm in size in just 6 minutes, and is therefore between 3 to 10 times faster than other systems. Its launch followed two years of extensive clinical use and evaluation in major centres around the world mainly treating liver and lung cancers
Microsulis Medical Limited Receives FDA 510(k) Clearance of Accu2i Percutaneous Microwave Tissue Ablation Device
*** August
High Power Microwave Tissue Ablation System Used to Destroy Liver and Lung Tumors DENMEAD, England--(BUSINESS WIRE)--Microsulis Medical Limited, the leading company in microwave technology for medical devices, today announced that the U.S. Food and Drug Administration (FDA) has provided the company 510(k) clearance to market the Acculis Accu2i percutaneous microwave tissue ablation (pMTA) system for the coagulation of soft tissue during surgical procedures. This innovative treatment allows physicians to apply precise microwave energy to ablate unwanted tissue masses. The system has already been in use in Europe treating liver and lung tumors via a small 1.8 mm needle puncture of the skin. By providing an alternative to “open surgery” patients avoid the risks associated with longer, more invasive surgical interventions.
“If the clinical performance of the system confirms the early promise of this technology, this advancement will lead to new treatment options for lung and liver cancer patients” “We are delighted to receive this clearance from the FDA and are looking forward to introducing the pMTA product to the U.S. market after seeing its success throughout Europe. Having transferred the product to the manufacturer in Europe we now have a system that we know is market-ready and tested,” said Stuart McIntyre, CEO of Microsulis Medical Limited. “Moreover this is the first high power 2.45 GHz system available and sets a new benchmark for such devices.”
According to the American Cancer Society, more than 450,000 Americans suffer from lung and liver cancer annually. Historically treatment options for these types of cancer have included one or a combination of treatments including surgical removal of the cancer, chemotherapy, radiofrequency ablation (RFA), or radiation therapy. Ablative therapies which aim to destroy tumors in-situ are limited by the number and size of the tumors that can be targeted and so it’s not an option in many cases due to the limited performance of existing RFA and microwave systems. However the Acculis Accu2i pMTA system is the first high power 2.45 GHz system that enables larger and faster ablations to be performed. This means that ablative therapy will now be available as an option for many more patients.
“If the clinical performance of the system confirms the early promise of this technology, this advancement will lead to new treatment options for lung and liver cancer patients,” said Dr. William Scott Helton, Chairman, Department of Surgery at Hospital of Saint Raphael, New Haven, Conn. “The Accu2i pMTA system allows physicians to deliver precise microwave energy to treat tumors up to 5cm in size in a very short period of time. It will add a significant additional tool into the armamentarium of oncologists, surgeons and radiologists treating patients with this illness.”
For more information about the Acculis Accu2i pMTA system, visit About Microsulis Medical Limited Founded in 1997, Microsulis Medical Ltd is a UK-based medical device company that exploits specialist intellectual property in medical microwave design to create therapeutic devices. The company was initially formed following research collaboration between Chemring and the University of Bath in 1993. The company leads the field in microwave technology for endometrial ablation, tumour ablation and venous occlusion. Part of MML, Acculis specialises in devices for oncology applications.
Investigators Evaluating Novel Monoclonal Antibody Bavituximab in Combination With Sorafenib "Our research has demonstrated that sorafenib increases the exposure of the highly immunosuppressive molecule phosphatidylserine (PS) on tumor vasculature, providing more of a specific target for bavituximab," said Adam C. Yopp, M.D., lead investigator of this trial and assistant professor of surgery at the University of Texas Southwestern Medical Center. "We are eager to determine if combining the growth-blocking mechanisms of sorafenib with the vascular-targeting and immune-reactivation mechanisms of bavituximab offers additive anti-tumor effects for patients with HCC." Currently, Peregrine's bavituximab is being evaluated in combination with chemotherapy in multiple Phase II trials in non-small cell lung cancer and advanced breast cancer, as well as a Phase Ib trial for hepatitis C virus (HCV) and HIV coinfection. Continue Reading........
The course of virologist Charlie Rices career changed with one phone call in 1989. Then at Washington University in St. Louis, Rice was the country's leading yellow fever expert. The voice on the other end of the line belonged to Stephen Feinstone, an FDA scientist asking about a vaccine for the disease that had just won agency approval. Yellow fever virus is a flavivirus. Feinstone wanted to know if Rice could help develop a vaccine to protect against another flavivirus: hepatitis C. “I can get interested in pretty much anything, I guess,” says Rice. Today, more than 20 years after Rice took that call, hepatitis C virus (HCV) infects about 170 million people worldwide, but those statistics may soon take a downward turn. Two protease inhibitors that recently completed late-stage clinical trials—telaprevir and boceprevir—are curing significant numbers of patients who may otherwise have suffered a lifetime of liver problems. Published studies reported profound responses to treatment with either of these drugs when used in combination with pegylated interferon (PegIFN) and ribavirin—the current standard, but often ineffective, therapy (J.G. McHutchison et al., NEJM, 360:1827-38, 2009 and P.Y. Kwo et al., Lancet, 376:705-16, 2010). Continue reading............
Hepatitis C GI-5005 Vaccine Elicits Immune Response in Some Patients In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
Sticking Fast To Foil Hepatitis C Biochemistry: Aiming beyond the active site of a virus's key protease yields selective blockers Carmen Drahl By targeting a noncatalytic cysteine, researchers have designed selective irreversible blockers of a protease enzyme essential for hepatitis C virus replication (Nat. Chem. Biol., DOI: 10.1038/nchembio.492). The work is the first demonstration that steering clear of the active site is a viable design strategy for drugs that react to form a covalent bond to proteases, a broad class of proteins that includes many drug targets. This strategy has already proven useful for blocking other proteins such as kinases. Continue reading...........
Hepatitis fears for hundreds of Scots after Spanish outbreak Matthew Holehouse 1 Dec 2010 Hundreds of dialysis patients in Scotland are being called in for screening amid fears they could have contracted the hepatitus C virus from two Scottish holidaymakers who became infected while undergoing treatment at a clinic in Spain. The male Scottish victims, one from the NHS Greater Glasgow and Clyde board area and one from the NHS Forth Valley board area, are understood to have received dialysis in September at the Centro Hemodiálisis Nefdial on Majorca. They returned to Britain unknowingly carrying the blood-borne disease – which can cause liver failure – and continued their treatment in Scotland. Health experts say they could have passed it to other dialysis patients in Scottish hospitals. Health Protection Scotland said the threat was “extremely low” because of the robust infection control measures in place in Scotland. However, 245 people who may have been treated in the same units as the two people in Scotland are being offered extra screening for hepatitis C. Continue Reading........
Ikaria® Begins Enrollment Of Pivotal Trial For LUCASSIN® 01 December 2010Ikaria, Inc. announced that it has enrolled the first patients in its pivotal Phase III trial for LUCASSIN® (terlipressin). The multi-center, randomized, placebo-controlled, double-blind trial is known as the REVERSE Trial... [read article]
Merck's Frazier Stresses Science, Innovation For Future By Thomas Gryta Published December 01, 2010 Dow Jones Newswires On Wednesday, Frazier highlighted anti-clotting drug vorapaxar that will have late-stage data in mid-2011 and "could have a significant impact on cardiovascular health." "We believe this could be a very important contributor," he said. He also talked about hepatitis C drug boceprevir, which has shown success in late-stage trials and may hit the market next year, as being an important new product. He noted that 170 million people world-wide have the liver disease and current treatments are toxic and less effective than boceprevir. But in order to get new products to the market, Merck will have to work with the Food and Drug Administration. Frazier praised the agency, noting that it needs more resources in the form of staffing and funding, but he also hinted that the drug review process is becoming a bit too cautious. Continue reading................
Ex-model loses Hep C payout action (UKPA) – 5 hours ago A former model who was infected with hepatitis C after being given a blood transfusion more than 20 years ago has lost her High Court bid to challenge the legality of a Government compensation scheme. A QC for Sharon Moore said at a recent hearing in London that it appeared the Department of Health was "looking for ways of not making payments" to a whole category of people accidentally given contaminated blood in the mid-1980s during "the worst treatment disaster in the history of the NHS". Continue reading...........
Researchers Report Surprising AIDS-Treatment Benefits, Prevention Strategy in Epidemic Regions of Africa Two teams of researchers at UC San Diego and other U.S. and African universities and the World Bank have documented significant spillover benefits of a drug therapy to combat AIDS symptoms and a novel prevention strategy that focuses on girls in Sub-Saharan Africa, an area with two-thirds of the world’s HIV infections.
Anti-Microbials Are a Common Cause of Drug-Induced Liver Injury and Failure, Study Suggests ScienceDaily (Nov. 30, 2010) — New research shows that anti-microbial medications are a common cause of drug-induced liver injury (DILI) leading to acute liver failure (ALF), with women and minorities disproportionately affected. While ALF evolves slowly, once it does occur a spontaneous recovery is unlikely; however liver transplantation offers an excellent survival rate. Full findings of this ten-year prospective study are published in the December issue of Hepatology, a journal of the American Association for the Study of Liver Diseases.
Health Forum Sees Sacrifices for Doctors, Insurers - December 01, 2010 (The New York Times News Service) -- Health care costs can't continue to rise rapidly without crippling the state's economy and public services. But efforts to rein them in will require new team-based health care payment and delivery approaches, which would demand sacrifices from hospitals, doctors, and insurers.
Foods May Help Ward Off Cold, Flu - December 01, 2010 (The Atlanta Journal-Constitution) -- The holiday season is upon us, and along with the festive lights and music, we often encounter the not-so-welcome sounds of coughing and sneezing.
Calcium, Vitamin D Changes Suggested - November 30, 2010 (The New York Times News Service) -- A long-awaited report from a panel of independent scientists recommends tripling the amount of vitamin D most Americans should take and small increases in calcium levels for children to build and maintain strong bones, but some specialists warned that the recommendations were flawed.
Public Release: 1-Dec-2010 Journal of Virology BUSM researchers show an oncolytic virus switches off cancer cell surival signal Researchers from Boston University School of Medicine have identified a mechanism by which specific viruses acting as oncolytic agents can enter and kill cancer cells. This finding, which is currently featured in an online edition of the Journal of Virology, could help lead to the development of more targeted treatments against many types of cancer. National Institutes of Health
Public Release: 1-Dec-2010 American Journal of Human GeneticsResearchers identify gene tied to extremely rare disorder that causes inflammation and loss of fatUT Southwestern Medical Center researchers have identified a gene responsible for a rare disease that results in severe joint stiffness, muscle loss, anemia and panniculitis-induced lipodystrophy, or JMP syndrome. National Institutes of Health
Public Release: 1-Dec-2010 Physics World Physicists use graphene to decode DNA Genome sequencing will have a profound effect on our understanding of genetic biology and could usher in a day when doctor and patient are able to review individual genome sequences to fully personalize medical treatment.
Vaccination Nation: One And Done BETHESDA, MD (Ivanhoe Newswire) -- This is something no one wants to hear. This month kicks off flu season! Sadly, you’re most at risk for the flu between the months of November and March. Full News Report »
BOSTON – A therapeutic vaccine against the hepatitis C virus was associated with a significantly higher sustained virologic response rate when added to standard-of-care treatment, and the findings justify further development of the vaccine, Dr. Paul Pockros reported at the annual meeting of the American Association for the Study of Liver Diseases. Dr. Paul J. Pockros
In the proof-of-concept trial, 133 patients infected with hepatitis C virus (HCV) genotype 1 were randomized to either triple therapy comprising the experimental GI-5005 vaccine, which is designed to elicit a T-cell response specific to HCV, along with pegylated interferon alfa-2b plus ribavirin (P/R), or the standard P/R therapy alone.
The primary outcome measure was sustained virologic response (SVR), defined as undetectable HCV RNA at 6 months after treatment, said Dr. Pockros of the Scripps Clinic in La Jolla, Calif. The 68 patients in the experimental group initially received monotherapy with the vaccine, consisting of five weekly injections followed by two monthly injections for a 12-week lead-in period, before progressing to the standard-of-care P/R treatment and once-monthly injections. The 65 patients in the control group received standard-of-care P/R treatment alone.
In both groups, the treatment duration was 48 weeks for treatment-naive patients and 72 weeks for those who had a poor or partial response to prior P/R treatment, said Dr. Pockros. Patients in whom prior P/R therapy induced no notable decrease in HCV viral load, as well as those in whom prior treatment initially resulted in undetectable HCV RNA followed by a viral rebound, were excluded from the analysis.
Among the study’s treatment-naive patients, 58% of those who received the vaccine achieved SVR, compared with 48% of those who received P/R alone. Among the prior poor and partial responders, the respective SVR rates in the vaccine and control groups were 17% and 5%, Dr. Pockros reported.
"There was a slight benefit in the treatment-naive and nonresponders, [but] this was numerical only and was not statistically significant," he said. However, the overall benefit in the vaccine vs. control groups was statistically significant, with respective SVR rates of 47% and 35%, he noted. The vaccine strategy appears to be safe. "The most common associated adverse events were mild, transient injection-site reactions," said Dr. Pockros. Additionally, he stated, "the discontinuation rates due to adverse events were comparable [13%] in both the triple-therapy and standard-of-care arms."
Of particular interest, Dr. Pockros noted, was the T-cell response in a subgroup of difficult-to-treat patients receiving the vaccine. Previous studies have suggested that patients carrying the T allele of the IL28 gene are at high risk of treatment failure with the standard interferon-based therapy. The T-cell response in vaccine-treated patients, as measured by interferon-gamma enzyme-linked ImmunoSpot assay, "mimicked what we saw with a virologic response," he said. "Four of five T/T allele patients had a T-cell response – one did not actually get treated – but none of the patients who received standard of care had a T-cell response."
This finding is consistent with the hypothesis that the GI-5005 vaccine corrects a fundamental deficit in cellular immunity in IL28B T/T genotype patients, he said. Although the findings need to be confirmed in additional studies with larger patient populations, the vaccine will likely be genotype specific, he noted.
Because the immune response is similar to that observed in HCV-infected patients who are able to clear the virus without treatment, future studies will evaluate the efficacy of monotherapy with the vaccine in genotype-specific patients, Dr. Pockros said. The proof-of-concept study was funded by GlobeImmune, manufacturer of the vaccine. Dr. Pockros disclosed financial relationships with GlobeImmune, Genentech, Vertex, Merck, Gilead, Abbott, Pfizer, Phenomix, Tibotec, Pharmasset, 3RT, Novartis, Johnson & Johnson, Achillon, Regulus, Debio, Zymogenetics, and Human Genome Sciences.
Recently, Merit Medical Systems (MMSI) received approval from the US Food and Drug Administration (FDA) for the phase III clinical trial protocol to treat primary liver cancer with QuadraSphere microsphere for delivery of doxorubicin.
The approval is significant since the late-stage study in the US will be the first to compare drug-eluting microspheres to conventional chemoembolization (cTACE) in the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer. At present, according to Merit Medical, there is no FDA-approved embolic for the treatment of liver cancer in the US. QuadraSphere is indicated for embolization of hypervascular tumors and peripheral arteriovenous malformations. While QuadraSphere has a long way to go before receiving the US approval, a similar product, HepaSphere is marketed in Europe since 2007 for embolization of HCC and hepatic metastases.
The phase III study is aimed at investigating HepaSphere/QuadraSphere microspheres for delivery of doxorubicin to treat HCC. While survival is the primary end-point of the study, secondary end-points include tumor response by mRECIST criteria, safety, resource utilization and adverse events. Approximately 500 patients are expected to be enrolled for the study at clinical sites across the US, Europe and South America.
Merit Medical had included microsphere products to its line of tumor treatment options with the acquisition of BioSphere Medical which was completed in September 2010. Through this acquisition, the company gained access to BioSphere's embolotherapy technology platform. This technology finds applications in treating uterine fibroids and primary liver cancer, representing a global market potential of $650 million and $380 million, respectively.
Viewing the untapped potential in the liver cancer market, it is expected that successful commercialization of microspheres in the US will be beneficial to Merit Medical over the long term. While liver cancer is the third leading cause of cancer deaths globally, its occurrence has increased with rise in hepatitis C infections, alcohol consumption and obesity. Although liver transplantation or tumor resection is considered a curative treatment; only 25% of liver cancers are diagnosed when they can be treated surgically. It has been witnessed that in cases where surgery is not a viable option, TACE has shown promising results.
Researchers engineer biological "devices" to program cells
Stanford bioengineer Christina Smolke, PhD, and colleagues have built biological "devices" capable of sensing disease states in cultured human cells and fine-tuning their own functions in response to the cell's internal signals, according to research recently published in Science. An article published today in the Stanford Report further describes the design and functionality of the new tools, which are called "sensor-actuator" devices:
Assistant Professor of Bioengineering Christina Smolke has engineered biological molecules that regulate a cell's behavior by adjusting their own forms and functions in response to the internal conditions of the cell. These tools can be used to facilitate medical research and biotechnology today and could one day be used as diagnostic and therapeutic aides. L.A. Cicero Christina Smolke
BY SUSAN YOUNG Imagine if your doctor could look for cancer in your body just by checking for green glowing cells, alerting her to the presence of the disease. Imagine further that she could convince any cancerous cells in your body to commit suicide, while leaving your healthy cells unaffected. In Friday's issue of Science, a Stanford researcher reported engineered biological "devices" that could one day offer these kinds of diagnostic and treatment options. The devices built by Assistant Professor of Bioengineering Christina Smolke, along with a graduate student and a postdoctoral researcher, can sense disease states in cultured human cells and fine-tune their own functions in response to a cell's internal signals.
These autonomous biological tools are called "sensor-actuator" devices because they sense what's happening in a cell and act upon what they detect.
The researchers built these devices by combining different pieces of DNA into one long stretch. The DNA is then put into cells that convert it to RNA, a slightly different version of genetic material that is frequently made by cells. The RNA molecule can then be read like a recipe by the cell's protein-making molecular machinery.
The sensor-actuator devices are built with efficient redesign in mind. Each piece of the device, whether the sensor or the protein-recipe actuator, can be swapped out for another version. This way, researchers can conveniently build a device to fit their particular needs. "You can fan out with lots of different outputs and you have lots of different inputs you could potentially link into," said Smolke. The input could be any number of protein signals inside a cell and the output could be instructions for the cell to create a molecule that's easily detected by a researcher – as in the case of the green-glowing cancer cells. Or the output could cause a diseased cell to kill itself.
The sensor part of the RNA molecule can detect whether a certain protein is present simply by binding to it. The proteins these devices detect are chemical messengers, communicating information gathered inside and outside of the cell into the nucleus, which acts like the cell's control center.
Smolke and her team used the molecular devices to sense disease-like states, such as inflammation and cancer, in cultured human cells. "We have a lot of these different signaling pathways in our cells and many diseases are associated with mistaken signaling through these pathways," said Smolke. The RNA sensor-actuator devices can "listen in" on the messages communicated by the cell and act accordingly. Depending on whether or not the device binds to the input protein, the RNA molecule could keep its original structure, or cut out a piece of itself and thus change the genetic information it contains.
When the RNA is read by the cell's protein-making machinery, the final product will depend on the RNA's information content. Powerful tool for cells The process by which the RNA device can remove part of itself is called "alternative splicing." Alternative splicing is an everyday process for many cells and is a powerful way to generate a diverse array of proteins inside a cell.
In the sensor-actuator devices described in the study, the optional piece of the RNA that could be cut out contained a "stop" message that instructed cells to stop making a protein before it was complete. When this "stop"-containing piece was removed, the device produced instructions for a whole and functional protein, one that, for instance, could glow green. In this way, the device could alter its output based upon the state of the cell.
"This is the first time a sensor-actuation device has been developed to respond to protein inputs and control an alternative splicing event linked to gene expression," said Smolke. "With the application of this device, you encode a certain level of intelligence that allows it to go into the cell and first assess whether the cell is diseased or not based upon disease markers. If yes, then it can then specifically activate therapeutic effects in that cell." One such therapeutic effect is the ability to specifically kill diseased cells. The researchers engineered an actuator module with an output that converted an inactive drug into an active form that causes cells to die. The sensor-actuator device only made the drug-activating output protein when the cell was diseased. Otherwise, the "stop" signal was left in the device and acted like a safety trigger preventing the death of healthy cells.
But the power of alternative splicing is not limited to just functional and non-functional outputs. "Instead of just yes/no, alternative splicing could modulate function," said Smolke. Proteins could be modified to have slightly different functions in response to different cell states. "There's a lot of richness in alternative splicing that could be used to develop more complex genetic circuits, beyond the demonstrated examples, that we might begin to implement in human cells," she said.
Smolke began the study at Caltech, where she was an assistant professor of chemical engineering. She moved to Stanford mid-project in 2009, where she completed much of the data analysis. Caltech student Stephanie Culler and postdoctoral researcher Kevin Hoff also contributed to the report.
The study was funded by the Caltech Joseph Jacobs Institute for Molecular Engineering for Medicine, the National Institutes of Health, the U.S. Department of Defense, the Alfred P. Sloan Foundation and the Bill and Melinda Gates Foundation. Susan Young is a science-writing intern at the Stanford News Service
Universal access, human rights theme of 22nd World AIDS Day
Today, on the 22nd World AIDS Day, people will gather to remember those they have lost, to support those living with HIV and to continue to fight for a cure.
County clinic stresses access Asbury group to honor dead By BONNIE DELANEY • STAFF WRITER • November 30, 2010
The theme of this year's day is "Universal Access and Human Rights" to stress the importance of access to HIV/AIDS prevention, treatment and care services. More than 33 million people are living with HIV/AIDS worldwide, said the Rev. Robert Kaeding, founder and director of The Center in Asbury Park, which provides housing for 25 adults with HIV/AIDS, along with an array of support services for those in the community. "So many people are living with the virus, yet AIDS is off the front page of the news," he added. "The best kind of prevention is talking about it and education. We need to remind people that there still is not a cure and that AIDS is still out there," Kaeding said. At 6:30 p.m., a candlelight walk will proceed from the Center in Asbury Park to Trinity Church to remember those who have lost their lives to the disease and those who are living with it. Leslie Terjesen, a spokeswoman for the Ocean County Health Department, said World AIDS Day is a great opportunity to raise awareness of the disease.
"We're home to the Ocean County AIDS Clinic and it is free to anyone who has HIV or AIDS," said Terjesen, adding that in addition to the rapid test, the clinic offers counseling, respite for caregivers, and support groups run by residents who lost their children to AIDS in the early 1990s Continue reading............
. SUMMARY: Vertex Pharmaceuticals announced last week that it has completed its submission of data to the U.S. Food and Drug Administration (FDA) in support of its New Drug Application for the oral hepatitis C virus (HCV) protease inhibitor telaprevir. Data from Phase 3 trials showed that the drug significantly improves sustained virological response rates when combined with pegyalted interferon plus ribavirin.
. SUMMARY: Medivir last week announced interim data from the Phase 2b ASPIRE trial, demonstrating that its investigational once-daily HCV protease inhibitor TMC435 (being developed jointly with Tibotec), when combined with pegyalted interferon plus ribavirin, increased the likelihood that treatment-experienced chronic hepatitis C patients would achieve undetectable HCV viral load at 4, 12, and 24 weeks, compared with standard therapy alone. Rates of undetectable HCV RNA at week 24 ranged from 78% for prior null responders to 94% for prior relapsers. Added to recently presented data from treatment-naive participants in the PILLAR trial, these findings indicate that TMC435 appears to work well for patients with or without prior treatment failure. Further follow-up is underway to see if viral suppression will be sustained 6 months after completion of therapy (sustained virological response, or SVR).
