- Newly Diagnosed
- All FDA Approved Drugs To Treat Hepatitis C
- 2017-HCV Genotypes/Treatment
- Epclusa® (Sofosbuvir/Velpatasvir)
- Harvoni® (Ledipasvir/Sofosbuvir)
- VIEKIRA XR/VIEKIRA Pak
- Not FDA Approved - Sofosbuvir/Velpatasvir/Voxilaprevir
- Not FDA Approved - Glecaprevir/Pibrentasvir (G/P)
- NOT FDA Approved - MK3 (MK-3682/grazoprevir/ruzasvir1)
- Cure - Achieving sustained virologic response (SVR) in hepatitis C
- FibroScan® Understanding The Results
- Is There A Natural Way To Improve Liver Fibrosis?
- Staging Cirrhosis
Tuesday, November 30, 2010
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:
Stanford researcher's engineered molecule changes itself to detect and attack diseased cells
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.
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
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
Latinos & HCV: unequal opportunity for treatment -
Irreversible inhibition of a protease central to hepatitis C infection; New HCV Protease AVL-192: Study (full text; published pdf attached) -
New HCV Drugs at AASLD -
Assessment of Hepatitis C Virus Attitudes Towards Treatment Among Methadone Maintenance Treatment Program Staff -
Ultra-Deep Sequencing of the NS3 and NS5B Regions Detects Pre-Existing Resistant Variants to Direct Acting Antivirals (DAA) in HCV Genotype 1 Treatment-Naïve Infected Patients -
World AIDS Day 2010 Brings News of Progress in Curbing HIV Epidemic
Smoking Raises Risk of Illness and Death for People with HIV
Human Protein Tetherin Disables Production of New Infectious HIV
Gilead Submits Rilpivirine (TMC278) Single-tablet Regimen for FDA Approval
Most Gay and Bisexual Men Worldwide Lack Access to HIV Prevention Services
IAS Calls on Pope to Support All Evidence-based HIV Prevention Methods
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).
Place In Subject of your email : Send me the E-mail Updates
Vertex submits application for hepatitis C drug
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Sign up for Blue Faery's quarterly e-newsletter to receive the latest updates about our activities. Visit our e-Newsletter Archives to view previous editions. If you have any HCC-related news that you would like us to feature in our quarterly e-newsletter, please email Andrea and put "Newsletter story" in the subject line.
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MatchingDonors.com may be able to help patients and donors with transplant related expenses not covered by insurance
From Medscape Medical News > Psychiatry
Authors and Disclosures
November 30, 2010 — Findings from a prospective cohort study released today suggest tricyclic antidepressants (TCAs) are associated with a 35% increased risk for cardiovascular disease (CVD), which is not explained by existing psychiatric illness.
However, researchers found no increased cardiac risk associated with selective serotonin reuptake inhibitors (SSRIs).
"This suggests that there may be some characteristic of tricyclics that is raising the risk," Mark Hamer, PhD, of University College London, United Kingdom, said in a release. "Tricyclics are known to have a number of side effects; they are linked to increased blood pressure, weight gain, and diabetes, and these are all risk factor for CVD," he adds.
Dr. Hamer told Medscape Medical News that clinicians need to "be cautious about prescribing TCAs, especially in people with other risk factors."
In the study, published online December 1 in the European Heart Journal, Dr. Hamer and colleagues assessed the association between antidepressant medication use and future risk for CVD in 14,784 Scottish adults with no known history of CVD.
Liver tumor being treated with SIR-Spheres
This new therapy is called Selective Internal Radiation Therapy also known as SIRT.
SIR-Spheres microspheres were developed in the 1980's in Perth, Western Australia. Since then, the product and the procedure has been refined and many hundreds of patients have been treated. SIR-Spheres microspheres received PMA approval by the Food and Drug Administration (FDA) in 2002.
SIR-Spheres microspheres are administered by a specially trained interventional radiologist. Your individual treatment plan will be reviewed by other specialists experienced in the treatment of liver tumors. The procedure is usually performed as an outpatient procedure under local sedation in the radiology suite. A small incision will be made in the patient's groin and a flexible catheter will be guided into the liver under x-ray vision. The catheter is moved through the hepatic artery and positioned by the interventional radiologist to allow for targeted infusion of the SIR-Spheres microspheres to the liver tumors. SIR-Spheres microspheres take about 15 minutes to be infused and the whole procedure takes about one hour from beginning to end.
After the procedure is completed you may be sent to have a special scan to check the level of radioactivity of the SIR-Spheres microspheres in your liver. You will be monitored for a few hours after the procedure and most patients are discharged within 24 hours. There are few precautions you and your family need to keep in mind the first week after treatment, with SIR-Spheres microspheres; there should be no close physical contact with others for longer than 2 hours, the patient should sleep in bed alone, there should be no contact with pregnant family members and children and pets should not sit on the patients lap. After a week the patient will be able to resume normal contact with family members.
SIR-Spheres microspheres therapy is regarded as a regional treatment; that is, the anti-cancer effect is concentrated in the liver and there is no effect on the cancer at other sites. SIR-Spheres microspheres are used to treat secondary liver cancer where the cancer originates in the bowel (colon) and then spreads to the liver. This type of cancer is called metastatic colorectal cancer. SIR-Spheres microspheres is generally not regarded as a cure, but has been shown to shrink the tumors more than chemotherapy alone. Quality of life can improve, and life expectancy may increase. For a small number of patients, treatment with SIR-Spheres microspheres can cause marked shrinkage of the liver tumor allowing for surgical removal at a later date.
The SIRFLOX study is an international research study designed to evaluate a new treatment option for patients with colorectal cancer that has undergone metastatic spread to the liver. The study is designed to evaluate whether FOLFOX chemotherapy in combination with Selective Internal Radiation Therapy is more effective than chemotherapy alone. This study represents the first time that these treatments have been assessed together as part of a randomised controlled study and as a first-line therapy (i.e. in patients who have not previously received chemotherapy for their liver metastases).
About the SIRFLOX study
The SIRFLOX study is an international research study designed to evaluate a new treatment option for patients with colorectal cancer that has undergone metastatic spread to the liver.
Click here (pdf, 1.168 kB) for additional information regarding the use of SIR-Spheres microspheres for the treatment of liver tumours. (Versions in German (pdf, 1.250 kB), French (pdf, 1.050 kB), Spanish (pdf, 1.260 kB))
What Is SIR-Spheres Microspheres ? Liver Cancer: Video Understanding SIR-Spheres microspheres - Whats Being Discussed ?
Studies Reconfirm Significant Benefits Regarding the Use of SIR-Spheres® Microspheres for the Treatment of Inoperable Liver Tumors
Sirtex Announces Latest Clinical Findings and Provides Updates on Research Initiatives
WILMINGTON, Mass.--(EON: Enhanced Online News)--Sirtex, a leading developer of targeted and innovative liver cancer therapies, provided an update on clinical initiatives regarding SIR-Spheres® microspheres.
Highlights include the results of two independent studies in Belgium and Italy published recently in the Journal of Clinical Oncology and the British Journal of Cancer, respectively. The studies reconfirmed evidence from earlier research that established “significant clinical benefits from the use of targeted radioactive SIR-Spheres microspheres as an effective option for patients with inoperable liver cancer.”
“These two independent studies provide further evidence that SIR-Spheres microspheres can improve clinical outcomes in a patient population with limited treatment options”
In addition to the two completed studies, Sirtex also released updates regarding a larger, independent global study currently enrolling patients at 40 sites including several in the United States. The SIRFLOX study, with a primary endpoint of Progression Free Survival, is a prospective randomized study looking at SIR-Spheres microspheres in combination with chemotherapy for first line treatment of patients with unresectable liver metastases from colorectal cancer.
Belgian Study Yields Positive Results for Patients with Metastatic Colon Cancer
Results of a randomized controlled 46-patient Belgian trial published in the Journal of Clinical Oncology revealed that in patients with liver metastases from colorectal cancer who had failed all available standard-of-care chemotherapy, SIR-Spheres microspheres more than doubled the time to progression in the liver (the primary endpoint of the study) from a median of 2.1 months in patients receiving chemotherapy alone to 5.5 months in patients receiving SIR-Spheres microspheres plus chemotherapy (p=0.003).1,2
SIR-Spheres microspheres also significantly extended the time to progression of disease anywhere in the body, from 2.1 months in the chemotherapy control arm to 4.5 months in patients in the combination arm (p=0.03), as well as significantly increasing disease control, from 35 percent to 85 percent, respectively (p=0.001).
For ethical reasons, the trial included a cross-over design for patients in the control arm following failure of chemotherapy alone. All patients in the control arm were reassessed for suitability for SIR-Spheres microspheres, with 43 percent of patients receiving Selective Internal Radiation Therapy (SIRT).
Median survival increased from 7.3 months in the chemotherapy control arm to 10 months in the SIR-Spheres microspheres plus chemotherapy arm.
Investigators noted that SIR-Spheres microspheres should be considered as a valid therapeutic option for patients with chemotherapy-refractory liver-limited metastatic colorectal cancer (mCRC).
Italian Multi-Center Study Produces Significant Response in Patients
At the same time, the results of a 50-patient, independent, multi-center Italian study published in the British Journal of Cancer showed SIR-Spheres microspheres produced a significant and meaningful response in patients with advanced inoperable liver tumors who had failed all available chemotherapy treatments.3,4 The study, conducted by the Italian Society of Locoregional Therapies in Oncology (SITILO), was the first single-arm, prospective clinical trial of SIR-Spheres microspheres in the salvage therapy of patients with mCRC who had been heavily pre-treated with chemotherapy.
The results revealed an overall response rate of 24 percent, which met the trial’s pre-determined criteria for significance, plus stable disease reported in a further 24 percent of patients.
In two patients, the tumors shrank sufficiently to permit surgeons to plan potentially curative surgery. The median overall survival for the trial was 12.6 months. Patients that responded to SIR-Spheres microspheres, or who had stable disease, experienced a significantly longer median survival compared to non-responders (16 months versus 8 months; p=0.0006), with 40 percent of the responders remaining alive at two years compared to none of the non-responders.
The investigators concluded that patients with liver-only or liver-dominant colorectal cancer metastases who had failed chemotherapy and who remained fit should be considered for radioembolization, which highlights the potential for SIR-Spheres microspheres to be used to provide meaningful clinical benefits in a greater number of patients than at present.
SIRFLOX Study Currently Enrolling
SIRFLOX is the first prospective randomized study looking at SIR-Spheres microspheres in combination with standard therapy for first line treatment, FOLFOX6 with or without bevacizumab, in patients with unresectable liver metastases from colorectal cancer. The primary endpoint of the study is Progression Free Survival.
The SIRFLOX study is open and enrolling at more than 40 sites worldwide. To date, 180 patients have enrolled with enrollment of 450 patients anticipated complete by the end of 2011. An independent data safety monitoring committee (IDSMC) recently finalized a safety analysis on the first 80 patients and found the study has no major safety issues that would preclude continuing as scheduled.
The aim of SIRFLOX is to determine if SIR-Spheres microspheres in combination with FOLFOX6 with or without bevacizumab can be considered a valid first line option for patients with liver-limited metastatic colorectal cancer.
A sister study, FOXFIRE, is underway in the United Kingdom. The study is identical in design except that the primary endpoint is Overall Survival. It is anticipated that data on over 800 patients from the two trials can be combined to determine an Overall Survival endpoint across both studies.
“These two independent studies provide further evidence that SIR-Spheres microspheres can improve clinical outcomes in a patient population with limited treatment options,” said Michael Mangano, President, Sirtex Medical Inc. “We are excited that the SIRFLOX trial is well underway in the United States. We believe that this study, along with FOXFIRE, will confirm that SIR-Spheres microspheres should be added to modern first-line chemotherapy for patients with metastatic colorectal cancer, to extend survival, in line with the clinical benefits seen in the two European studies in patients who have failed all available treatment options.”
SIR-Spheres microspheres therapy is available to patients throughout the United States and a full list of treating sites can be found at www.sirflox.com/home.
About Selective Internal Radiation Therapy (SIRT)
About Selective Internal Radiation Therapy (SIRT) using SIR-Spheres microspheres Selective Internal Radiation Therapy (SIRT), also known as radioembolization, is a novel treatment for inoperable liver cancer that delivers high doses of radiation directly to the site of tumors. In a minimally-invasive treatment, millions of radioactive SIR-Spheres microspheres are infused via a catheter into the liver where they selectively target liver tumors with a dose of internal radiation up to 40 times higher than conventional radiotherapy, while sparing healthy tissue.
Clinical trials have confirmed that liver cancer patients treated with SIR-Spheres microspheres have response rates higher than with other forms of treatment, resulting in increased life expectancy, greater periods without tumor activity, and improved quality of life. SIRT has been found to shrink liver tumors more than chemotherapy alone.
SIR-Spheres microspheres are approved for use in Australia, the United States of America (FDA approval), and the European Union (CE Mark) and additionally supplied in countries such as Hong Kong, Malaysia, Singapore, Thailand, Taiwan, India, Israel and Turkey with approximately 13,500 treatments worldwide.
Manufactured by Sirtex, SIR-Spheres microspheres are the only FDA-approved microsphere radiation therapy for the treatment of colorectal liver metastases. Sirtex Medical Inc.’s SIR-Spheres microspheres are indicated for the treatment of non-resectable metastatic colorectal cancer in combination with intra-arterial FUDR chemotherapy. Information regarding other disease states or agents in combination with this device, that is presented in peer-reviewed literature or medical meetings may differ from the approved USA indications as per the labeling for the product.
1. Hendlisz A, Van den Eynde M, Peeters M et al. Phase III trial comparing protracted intravenous fluorouracil infusion alone or with yttrium-90 resin microspheres radioembolization for liver-limited metastatic colorectal cancer refractory to standard chemotherapy. Journal of Clinical Oncology 2010; 28: 3687–3694.
2. The clinical trial was conducted at the following university hospitals:
Institut Jules Bordet, Brussels, Belgium
Universitair Ziekenhuis Gent, Gent, Belgium
University Hospital Gasthuisberg, Leuven, Belgium
3. Cosimelli M, Golfieri R, Cagol PP et al. Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases. British Journal of Cancer 2010; 103: 324–331.
4. The SITILO clinical trial was conducted at the following hospitals:
Regina Elena Cancer Institute, Rome, Italy
University of Bologna, Bologna, Italy
University of Udine, Udine, Italy
Fondazione Pascale Cancer Institute, Naples, Italy
® SIR-Spheres is a Registered Trademark of Sirtex SIR-Spheres Pty Ltd
of Fleishman-Hillard on Behalf of SirtexAndrea Moody, 919-457-0743
Additional News /Liver Cancer and Treatment
Nov 30 th
Dr. Banker previously performed the procedure when he worked at the University of Mississippi. He's excited to bring the technology to Toledo. "The procedure requires getting into the hepatic artery in the liver and injecting small particles with high levels of radiation directly into the tumors and destroying the tumors from the inside out," he explained....
Jim Belushi Chicago Abc Yes Liver Cancer Symposium
November News Liver Cancer and Treatments
Apricus Biosciences Inc. said Monday it reached an agreement with the Food and Drug Administration on the design of a trial for a potential liver cancer drug, making approval more likely if the study is successful.
SOUTH JORDAN, Utah, Nov. 29, 2010 (GLOBE NEWSWIRE) --
The Food and Drug Administration (FDA) has approved Merit Medical Systems, phase 3 clinical trial protocol to treat primary liver cancer with QuadraSphere(TM) Microspheres (hqTACE) for delivery of doxorubicin. The clinical trial will involve U.S. and international interventional radiologists who treat patients with localized, unresectable hepatocellular carcinoma (HCC), the most common form of liver cancer. The FDA action will result in the first phase 3 study in the U.S. comparing drug-eluting microspheres to conventional chemoembolization (cTACE) in the treatment of hepatocellular carcinoma. Currently in the U.S. there is no FDA-approved embolic for the treatment of liver cancer.
Hundreds of dialysis patients are being given extra screening for hepatitis C after two people contracted it following treatment in the same unit in Spain.
The patients, one from the NHS Greater Glasgow and Clyde board area and one from the NHS Forth Valley board area, were found to be infected with hepatitis C on return from their holiday.
They had both received dialysis in the same unit in Spain, which has now been closed as a precaution.
Health Protection Scotland (HPS) said that the risk of the pair passing the infection on to any other dialysis patients in the health board areas is "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 as a precaution.
Professor David Goldberg, consultant epidemiologist at Health Protection Scotland, said: "We are undertaking this additional testing purely as a precaution.
Such patients can be at risk because dialysis is an invasive procedure.
An international investigation is under way to pinpoint the source of the infections.
Caleco Pharma Corp. Files Amendment To EU Patent Office Application
2010, 9:00 am EST
LONG VALLEY, NEW JERSEY--(Marketwire - 11/30/10) - Caleco Pharma Corp. ("Caleco") (OTC.BB:CAEH - News)(Frankfurt:T3R - News)(WKN: A0N9Y0) (www.calecopharmacorp.com), a diversified healthcare company with biopharmaceutical and consumer health product development programs that develop products derived from natural sources such as plant extracts, today reports that it has amended its intellectual property (IP) filing with the European Patent Office in The Hague to further secure and strengthen Caleco's anti-viral pipeline.
In response to the EU Patent Office's Examination Report, Caleco reports that the company's European Patent Application number 08725530.3 is amended with regard to compositions comprising derivatives and derivative combinations of Lamiridosin and Iridoid for treatment of Hepatitis C.
The molecular specifications required in these amendments resulted in the exclusion of certain derivative claims. However, these claims will not be abandoned, but instead, these claims will be pursued through one or more divisional applications.
John Boschert, Caleco's CEO, said, "By amending our filing we are seeking to solidify our intellectual property position in the billion dollar Hepatitis C and anti-viral marketplace. We plan to continue to pursue a broader pipeline of semi-synthetic derivatives that will be prepared for further testing in 2011. The Hepatitis C patient population remains greatly underserved by existing treatment options and we are eager to move these compounds into the next stage of development."
About Caleco Pharma Corp.
Caleco is focused on the ongoing research and development of its pipeline of over-the-counter and prescription medications including its proprietary antiviral and "Liver Health" OTC formulations. In addition Caleco is developing Dermatological Products based on the active ingredients found in its proprietary formulation. Caleco's intellectual property covering the Liver Health formulations and derivatives consists of patent applications in the United States, Europe and Canada and four European Drug Master File applications.
Caleco's shares are traded in the United States on the OTC Bulletin Board (OTC.BB:CAEH - News) and in Germany on the Frankfurt Stock Exchange (Frankfurt:T3R - News)(WKN: A0N9Y0).
This press release may contain, in addition to historic information, forward-looking statements. These statements may involve known and unknown risks and uncertainties and other factors that may cause the actual results to be materially different from the results implied herein. In particular, there are no assurances that: (i) the United States Patents and Trademarks Office and the European Union Patent office will grant Caleco a patent in connection with its current patent applications; (ii) Caleco will be able to manufacture and produce its products or that its products will be effective; (iii) Caleco Pharma Europe will be able to successfully distribute Lamiridosin in Europe; (iv) Caleco will be able to carry out any pre-clinical or clinical trials of its products; (v) Caleco will be able to obtain additional financing in order to meet the costs of the clinical studies of the "Liver Health" formulation; and (vi) Caleco will be able to control the costs of the clinical studies of the "Liver Health" formulation. Readers are cautioned not to place undue reliance on the forward-looking statements made in this press release.
Contacts:BlueWater Advisory Group - Investor RelationsBryan CraneManaging Director805-426-5090
Pharmasset Initiates Dosing in a Combination Study of PSI-7977 and PSI-938 for Chronic Hepatitis C
- Phase 1 combination study of a pyrimidine (PSI-7977) and purine (PSI-938) nucleotide analog in patients with chronic hepatitis C- Interim data expected in first quarter of 2011
PRINCETON, N.J., Nov. 30, 2010 /PRNewswire-FirstCall/ -- Pharmasset, Inc. (Nasdaq: VRUS) announced today that dosing has begun in Part 2 of a Phase 1 study. This is the first clinical study combining a purine (PSI-938) and a pyrimidine (PSI-7977) nucleotide analog for HCV, and is designed to evaluate once daily doses of PSI-7977 and PSI-938 in patients with HCV who have not been treated previously.
"We are excited to be initiating this combination study with two proprietary nucleotide analogs for HCV," stated Michelle Berrey, MD, MPH, Pharmasset's Chief Medical Officer. "Based on our in vitro data, we believe the combination of two nucleotide analogs could provide potent antiviral activity across multiple HCV genotypes and could also have a higher barrier to resistance compared to other DAA combinations. We believe nucleotide analogs have a number of key attributes that may make them ideal partners for other DAA combinations, in addition to a 'nuc-nuc' combination."
About the Phase 1 Trial
In Part 1 of the Phase 1 multiple ascending dose study of PSI-938, suppression of HCV RNA below the limit of detection (LOD, less then 15 IU/mL) was observed in over half of the patients who received PSI-938 at daily doses of 200 mg or 300 mg for seven days. Part 2 of the study is designed to evaluate the combination of PSI-938 and PSI-7977. The primary objective is to assess the safety, tolerability and pharmacokinetics of PSI-938 administered alone for 14 days, and in combination with PSI-7977 for 7 to 14 days. The secondary objective is to evaluate viral kinetics of HCV RNA during monotherapy and combination nucleotide dosing.
We expect to report preliminary results from Part 2 of this Phase 1 study during the first quarter of calendar year 2011. We also expect to initiate a Phase 2 study of PSI-938 in combination with PSI-7977 during mid-2011. This Phase 2 study proposes to explore durations of PSI-938 and PSI-7977 in interferon-free combinations with an SVR endpoint.
Pharmasset is a clinical-stage pharmaceutical company committed to discovering, developing, and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis C virus (HCV). Our research and development efforts focus on nucleoside/tide analogs, a class of compounds which act as alternative substrates for the viral polymerase, thus inhibiting viral replication. We currently have four clinical-stage product candidates. RG7128, a cytosine nucleoside analog for chronic HCV infection, is in two Phase 2b clinical studies in combination with Pegasys(R) plus Copegus(R) and is also in the INFORM studies, the first series of studies designed to assess the potential of combinations of small molecules without Pegasys(R) and Copegus(R) to treat chronic HCV. These clinical studies are being conducted through a strategic collaboration with Roche. Our other clinical stage HCV candidates include PSI-7977, an unpartnered uracil nucleotide analog that has recently initiated dosing in a Phase 2b study in patients with HCV genotypes 1, 2, or 3, and PSI-938, an unpartnered guanosine nucleotide analog which recently completed a 7-day monotherapy study. We also have in our pipeline an additional purine nucleotide analog, PSI-661, in advanced preclinical development.
Richard E. T. Smith, Ph.D.
VP, Investor Relations and Corporate Communications
Office +1 (609) 613-4181
Pharmasset "Safe Harbor" Statement under the Private Securities Litigation Reform Act of 1995: Statements in this press release that are not historical facts are "forward-looking statements," that involve risks, uncertainties, and other important factors, including, without limitation, the risk of cessation or delay of any of the ongoing or planned clinical trials and/or our development of our product candidates, the risk that the results of previously conducted studies involving our product candidates will not be repeated or observed in ongoing or future studies involving our product candidates, the risk that our collaboration with Roche will not continue or will not be successful, and the risk that any one or more of our product candidates will not be successfully developed and commercialized. For a discussion of risks, uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in our Annual Report on Form 10-K for the fiscal year ended September 30, 2010 filed with the Securities and Exchange Commission and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the Securities and Exchange Commission.
Embryonic stem cells - Embryonic stem cells include those found within the embryo, the fetus or the umbilical cord blood. Depending upon when they are harvested, embryonic stem cells can give rise to just about any cell in the human body.
Adult stem cells - Adult stem cells can be found in infants, children and adults. They reside in already developed tissues such as those of the heart, brain and kidney. They usually give rise to cells within their resident organs.
Induced pluripotent stem cells (IPSC)- These stem cells are adult, differentiated cells that have been experimentally "reprogrammed" into a stem cell-like state.
So how do all these types of stem cells work? And what are their potential uses? Let's find out -- starting with embryonic stem cells.
Once an egg cell is fertilized by a sperm, it will divide and become an embryo. In the embryo, there are stem cells that are capable of becoming all of the various cell types of the human body. For research, scientists get embryos in two ways. Many couples conceive by the process of in vitro fertilization. In this process, a couple's sperm and eggs are fertilized in a culture dish. The eggs develop into embryos, which are then implanted in the female. However, more embryos are made than can be implanted. So, these embryos are usually frozen. Many couples donate their unused embryos for stem cell research
The second way in which scientists get embryos is therapeutic cloning. This technique merges a cell (from the patient who needs the stem cell therapy) with a donor egg. The nucleus is removed from the egg and replaced with the nucleus of the patient's cell. (For a detailed look at the process, see How Cloning Works) This egg is stimulated to divide either chemically or with electricity, and the resulting embryo carries the patient's genetic material, which significantly reduces the risk that his or her body will reject the stem cells once they are implanted.
Both methods -- using existing fertilized embryos and creating new embryos specifically for research purposes -- are controversial. But before we get into the controversy, let's find out how scientists get stem cells to replicate in a laboratory setting in order to study them.
When an embryo contains about eight cells, the stem cells are totipotent - they can develop into all cell types. At three to five days, the embryo develops into a ball of cells called a blastocyst. A blastocyst contains about 100 cells total and the stem cells are inside. At this stage, the stem cells are pluripotent - they can develop into almost any cell type.
To grow the stem cells, scientists remove them from the blastocyst and culture them (grow them in a nutrient-rich solution) in a Petri dish in the laboratory. The stem cells divide several times and scientists divide the population into other dishes. After several months, there are millions of stem cells. If the cells continue to grow without differentiating, then the scientists have a stem cell line. Cell lines can be frozen and shared between laboratories. As we will see later, stem cell lines are necessary for developing therapies
Today, many expectant mothers are asked about umbilical cord banking -- the process of storing umbilical cord blood after giving birth. Why would someone want to do that? Once a mother gives birth, the umbilical cord and remaining blood are often discarded. However, this blood also contains stem cells from the fetus. Umbilical cord blood can be harvested and the embryonic stem cells grown in culture. Unlike embryonic stem cells from earlier in development, fetal stem cells from umbilical cord blood are multipotent - they can develop into a limited number of cell types.
Now that you have a better understanding of embryonic stem cells, let's look at adult stem cells.
You can think of adult stem cells as our built-in repair kits, regenerating cells damaged by disease, injury and everyday wear and tear. These undifferentiated cells reside among other differentiated cells in a tissue or organ; they divide and become specialized to repair or replace the surrounding differentiated cells. A common example of adult stem cells is hemopoietic stem cells, which are found in red bone marrow. These stem cells differentiate into various blood cells (red blood cells, lymphocytes, platelets-- see How Blood Works for more information). For example, red blood cells are not capable of reproducing and survive for about 28 days. To replace worn-out red blood cells, hemopoietic stem cells in the bone marrow divide and differentiate into new red blood cells
Bone marrow also contains a second type of adult stem cell known as a stromal or mesenchymal stem cell. Stromal stem cells become bone, cartilage, fat and connective tissues found in bone. Adult stem cells have also been found in many other tissues such as the brain, skeletal muscle, blood vessels, skin, liver, teeth and the heart. Regardless of the source, adult stem cells are multipotent - they can develop into a limited number of cell types.
Although adult stem cells exist in many tissues, their numbers are small, perhaps one adult stem cell for every 100,000 surrounding cells. These stem cells look like the surrounding cells, so it's difficult to tell them apart. But researchers have developed an interesting way to identify them by "lighting them up." All cells have unique proteins on their surface called receptors. Receptors bind chemical messages from other cells as part of cell-to-cell communication. Researchers use these receptors -- or markers -- to identify and isolate adult stem cells by "tagging" the chemical messages that bind to those specific receptors on the stem cell with fluorescent molecules. Once the fluorescent chemical message binds to the receptor on the surface of the stem cell, the stem cell will "light up" under fluorescent light. The "lighted" stem cell can then be identified and isolated.
Like embryonic stem cells, adult stem cells can be grown in culture to establish stem cell lines.
Adult stem cells were once believed to be more limited than embryonic stem cells, only giving rise to the same type of tissue from which they originated. But new research suggests that adult stem cells may have the potential to generate other types of cells, as well. For example, liver cells may be coaxed to produce insulin, which is normally made by the pancreas. This capability is known as plasticity or transdifferentiation
It used to be believed that there were only two types of stem cells -- embryonic and adult -- but there's another kid on the stem cell block. Keep reading to learn about this "new" type: the induced pluripotent stem cell
Induced Pluripotent Stem Cells (IPSCs)
Whether from embryos or adult tissues, stem cells are few. But many are needed for cell therapies. There have been ethical and political problems with using embryonic stem cells -- so if there were a way to get more stem cells from adults, it might be less controversial. Enter the IPSC.
Every cell in the body has the same genetic instructions. So what makes a heart cell different from a liver cell? The two cells express different sets of genes. Likewise, a stem cell turns on specific sets of genes to differentiate into another cell. So, is it possible to reprogram a differentiated cell so that it reverts back to a stem cell? In 2006, scientists did just that. They used a virus to deliver four stem cell factors into skin cells. The factors caused the differentiated stem cells to go into an embryonic-stem-cell-like state. The resulting cells, called induced pluripotent stem cells (IPSCs), shared many characteristics with human embryonic stem cells. The structures of IPSCs were similar, they expressed the same markers and genes, and they grew the same. And the researchers were able to grow the IPSCs into cell lines.
There are many more differentiated cells in the human body than stem cells, embryonic or adult. So, vast amounts of stem cells could be made from a patient's own differentiated cells, like skin cells. Making IPSCs does not involve embryos, so this would circumvent the ethical and political issues involved in stem cell research. However, making ISPSCs is a recent development, so scientists need to do more research before they can be used for therapies. First, we need to understand the "reprogramming" process better. And then we need to investigate whether IPSCs are just similar enough or are actually identical to embryonic stem cells. Current research is focused on these questions, but reprogramming cells to make IPSCs has great potential.
Now that you have a good idea of what stems cells are and how they work, let's see how they can be used to treat diseases
Save Those Teeth
Dentists usually discard wisdom teeth after they've been extracted -- but maybe they should start saving them; they just might be useful in make stem cells. Recently, a group of Japanese scientists made induced pluripotent stem cells (IPSCs) from the tooth pulp of extracted wisdom teeth. They used viruses to deliver stem cell factors to mesenchymal stromal cells isolated from the pulp of third molars. The resulting IPSCs were similar to embryonic stem cells.
In 2003, an NIH researcher, Sangtao Shi, extracted stem cells from his daughter's baby teeth. The stem cells grew in culture and could form bone when implanted into mice. Potentially, you could bank stem cells from your teeth for future use, but it would be an expensive process.
Maybe that's what the tooth fairy does with all those teeth?
Using Stem Cells to Treat Disease
Stem-cell-based therapies are not new. The first stem-cell-based therapy was a bone marrow transplant used to treat leukemia. In this procedure, the patient's existing bone marrow is destroyed by radiation and/or chemotherapy. Donor bone marrow is injected into the patient and the bone marrow stem cells establish themselves in the patient's bones. The donor bone marrow cells differentiate into blood cells that the patient needs. Often, the patient must take drugs to prevent his or her immune system from rejecting the new bone marrow. But this procedure uses existing hemopoietic stem cells. How would you use stem cell lines? Let's look at how stem cells might be used to treat heart failure.
Ideally, to treat a failing heart, scientists could stimulate stem cells to differentiate into heart cells and inject them into the patient's damaged heart. There, the new heart cells could grow and repair the damaged tissue. Although scientists cannot yet direct stem cells to differentiate into heart cells, they have tested this idea in mice. They have injected stem cells (adult, embryonic) into mice with damaged hearts. The cells grew in the damaged heart cells and the mice showed improved heart function and blood flow.
In these experiments, exactly how the stem cells improved heart function remains controversial. They may have directly regenerated new muscle cells. Alternatively, they may have stimulated the formation of new blood vessels into the damaged areas. And the new blood flow may have stimulated existing heart stem cells to differentiate into new heart muscle cells. These experiments are currently being evaluated.
One major obstacle in stem cell use is the problem of rejection. If a patient is injected with stem cells taken from a donated embryo, his or her immune system may see the cells as foreign invaders and launch an attack against them. Using adult stem cells or IPSCs could overcome this problem somewhat, since stem cells taken from the patient would not be rejected by his or her immune system. But adult stem cells are less flexible than embryonic stem cells and are harder to manipulate in the lab. And IPSC technology is too new for transplantation work.
Finally, by studying how stem cells differentiate into specialized cells, the information gained can be used to understand how birth defects occur and possibly, how to treat them.
So, if there's so much potential in stem cell research, why all the controversy?
Let's investigate the current ethical and political issues.
Stem Cell Research Controversy
Stem Cell Research Advocates
Since 1991, when he was diagnosed with Parkinson's disease (a degenerative brain disorder that affects movement), actor Michael J. Fox has been a vocal proponent for stem cell research. His foundation has donated more than $205 million to help fund Parkinson's research [source: Michael J. Fox Foundation]. Fox and his foundation are hoping that scientists will one day be able to coax stem cells into producing dopamine, a chemical in the body that is deficient in patients with Parkinson's disease. Former first lady Nancy Reagan also became an advocate for stem cell research when her husband, former President Ronald Reagan, was stricken with Alzheimer's, another degenerative brain disease. He died of Alzheimer's in the summer of 2004.
Stem cell research has become one of the biggest issues dividing the scientific and religious communities around the world. At the core of the issue is one central question: When does life begin? At this time, to get stem cells that are reliable, scientists either have to use an embryo that has already been conceived or else clone an embryo using a cell from a patient's body and a donated egg. Either way, to harvest an embryo's stem cells, scientists must destroy it. Although that embryo may only contain four or five cells, some religious leaders say that destroying it is the equivalent of taking a human life. Inevitably, this issue entered the political arena.
In 1996, Congress passed a rider to the federal appropriations bill called the Dickey-Wicker amendment. Representatives Jay Dickey and Roger Wicker proposed banning the use of federal monies for any research in which a human embryo is created or destroyed. Federal monies are a primary source of funding for stem cell research. The amendment has been renewed every year since that time.
In 2001, President George W. Bush further restricted federal stem cell research. In an executive order, Bush stated that federal funds could only be used for research on human embryonic stem cell lines that had already been established (only 22 cell lines). This prevented researchers from creating more embryonic stem cell lines for research.
In 2009, President Barack Obama issued an executive order to expand embryonic stem cell research. Obama's administration allowed federal funding of embryonic stem cell research if the following conditions applied:
The cell line was one of the 22 in existence during the Bush administration or was created from embryos that had been discarded after in vitro fertilization procedures.
The donors of the embryos were not paid in any way.
The donors clearly knew that the embryos would be used for research purposes prior to giving consent.
According to the administration, the new policy did not violate the Dickey-Wicker amendment because the money did not finance the creation of new embryos (they had already been created by private means) and did not finance the destruction of them.
In 2009, two researchers from Boston, Dr. James Sherley of the Boston Biomedical Research Institute and Dr. Theresa Deisher of the Ava Maria Biotechnology Company, and other agencies filed a lawsuit against the government. Initially, the lawsuit was dismissed because the judge ruled that the plaintiffs had no legal standing (i.e. they were not affected materially by the new rules). However, a court of appeals overturned the initial ruling. The two scientists remained plaintiffs. The scientists claimed that, because they used adult stem cells exclusively in their research, the new rules would increase competition for federal research dollars, thereby affecting their ability to obtain funding. Federal Judge Royce Lamberth upheld the appeals court ruling. He placed an injunction preventing the new rules from going into place. He claimed that the rules violated the Dickey-Wicker amendment because embryos must be destroyed in the process of creating embryonic stem cell lines.
In September 2010, The New York Times reported that the U.S. Court of Appeals ruled that federal funding of embryonic stem cell research could continue under the new rules while the court considers Judge Lamberth's ruling [source: New York Times]. This ruling allows researchers to continue feeding embryonic stem cell cultures, experimenting with mice, and other research activities until this court rules, the U.S. Supreme Court weighs in, or Congress passes legislation that clarifies the issues. In the meantime, stem cell research and the careers of stem cell researchers hang on a legal roller coaster. Although stem cells have great potential for treating diseases, much work on the science, ethical and legal fronts remains.
For more on stem cells, investigate the links below
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Fox 31 KDVR.com - 3 days ago
President Barack Obama has allowed government-funded research on embryonic stem cells but a federal appeals court is considering whether that violates a ...
Los Angeles Times - Nov 21, 2010
But California's stem cell agency quickly found itself mired in another form of politics: legislators and government watchdogs criticized the program for ...
Centers for Disease Control, Heart Failure Fact Sheet, (accessed 10/25/2010), http://www.cdc.gov/dhdsp/library/fs_heart_failure.htm
Dunn, Kyla, NOVA: The Politics of Stem Cell Research (accessed 10/29/2010) http://www.pbs.org/wgbh/nova/body/stem-cells-politics.html
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Michael J. Fox Foundation. October 6, 2010 Press Release "Michael J. Fox Foundation Announces over $10 Million in Fund http://www.michaeljfox.org/newsEvents_mjffInTheNews_pressReleases_article.cfm ?ID=446
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Parkinson's Disease Foundation, Statistics on Parkinson's (accessed 10/26/2010) http://www.pdf.org/en/parkinson_statistics .
Wright, Laura, 2003, Potent Stem Cells Found in Baby Teeth, Scientific American online (accessed 10/28/2010) http://www.scientificamerican.com/article.cfm?id=potent-stem-cells-found-i
Also See : Nov 2010 Salk scientists discovered how stem cells respond to nutrient availability