J Hepatol. 2011 May 19. [Epub ahead of print]
Huang CF, Huang JF, Yang JF, Hsieh MY, Lin ZY, Chen SC, Wang LY, Juo SH, Chen KC, Chuang WL, Kuo HT, Dai CY, Yu ML.
Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
BACKGROUND: A substantial proportion of hepatitis C virus genotype 1 (HCV-1) patients achieved a sustained virological response (SVR, HCV RNA seronegative throughout 24 weeks of post-treatment follow-up) after 24 weeks peginterferon/ribavirin therapy. We explored the role of interleukin-28B genotype in identifying patients who responded to the regimen.
METHODS: Interleukin-28B rs8099917 genotype was determined in 226 HCV-1 patients with 24 weeks peginterferon/ribavirin.
RESULTS: Comparing to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, HCV RNA seronegative at treatment week 4, 54.0% vs. 17.9%, P<0.001) and SVR (64.7% vs. 25.6%, P<0.001) rates, and lower relapse rate (28.0% vs. 54.5%, P=0.01). Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/ 95% confidence intervals [OR/CI]: 6.24/2.34-16.63), followed by lower viral loads (OR/CI: 5.29/2.81-9.93) and age (OR/CI:0.94/0.91-9.97). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 22.23/9.22-53.58), followed by the carriage of rs8099917 TT genotype (OR/CI: 3.38/1.18-9.65), lower viral loads (OR/CI: 2.23/1.00-4.93) and ribavirin exposure dose (OR/CI: 1.17/1.06-1.30). The determinant power of rs8099917 genotype on SVR was mainly restricted to non-RVR patients, particularly those with higher baseline viral loads. Combination of the two pretreatment predictors, interleukin-28B genotype and baseline viral loads, could predict treatment efficacy with a positive predictive value of 80% and a negative predictive value of 91%.
CONCLUSIONS: Interleukin-28B genotype could help identifying patients who are or are not candidates for an abbreviated regimen before treatment.
Copyright © 2011. Published by Elsevier B.V.
Source
July 3, 2011
Oral combination therapy: Future hepatitis C virus treatment?
J Hepatol. 2011 May 19. [Epub ahead of print]
Hézode C.
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
Abstract
COMMENTARY ON:: Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): A randomised, double-blind, placebo-controlled, dose-escalation trial. Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, Elston R, Ipe D, Morcos PN, Baher L, Najera I, Chu T, Lopatin U, Berrey MM, Bradford W, Laughlin M, Shulman NS, Smith PF. Lancet 2010 Oct 30;376(9751):1467-75. Reprinted from The Lancet, Copyright (2010), with permission from Elsevier. http://www.ncbi.nlm.nih.gov/pubmed/20951424
BACKGROUND: Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs-RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor-in patients with chronic HCV infection.
METHODS: Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13days oral combination treatment with RG7128 (500 or 1000mg twice daily) and danoprevir (100 or 200mg every 8h or 600 or 900mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo. Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov., NCT00801255.
FINDINGS: Eighty-eight patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose). The median change in HCV RNA concentration from baseline to day 14 ranged from -3.7 to -5.2 log(10)IU/ml in the cohorts that received 13days of combination treatment. At the highest combination doses tested (1000mg RG7128 and 900mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was -5.1 log(10)IU/ml (IQR-5.6 to -4.7) in treatment-naive patients and -4.9 log(10)IU/ml in previous standard of care null responders (-5.2 to -4.5) compared with an increase of 0.1 log(10)IU/ml in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.
INTERPRETATION: This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV.
Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Source
Hézode C.
Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France; INSERM U955, Créteil, France.
Abstract
COMMENTARY ON:: Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): A randomised, double-blind, placebo-controlled, dose-escalation trial. Gane EJ, Roberts SK, Stedman CA, Angus PW, Ritchie B, Elston R, Ipe D, Morcos PN, Baher L, Najera I, Chu T, Lopatin U, Berrey MM, Bradford W, Laughlin M, Shulman NS, Smith PF. Lancet 2010 Oct 30;376(9751):1467-75. Reprinted from The Lancet, Copyright (2010), with permission from Elsevier. http://www.ncbi.nlm.nih.gov/pubmed/20951424
BACKGROUND: Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs-RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor-in patients with chronic HCV infection.
METHODS: Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13days oral combination treatment with RG7128 (500 or 1000mg twice daily) and danoprevir (100 or 200mg every 8h or 600 or 900mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo. Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov., NCT00801255.
FINDINGS: Eighty-eight patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose). The median change in HCV RNA concentration from baseline to day 14 ranged from -3.7 to -5.2 log(10)IU/ml in the cohorts that received 13days of combination treatment. At the highest combination doses tested (1000mg RG7128 and 900mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was -5.1 log(10)IU/ml (IQR-5.6 to -4.7) in treatment-naive patients and -4.9 log(10)IU/ml in previous standard of care null responders (-5.2 to -4.5) compared with an increase of 0.1 log(10)IU/ml in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations.
INTERPRETATION: This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV.
Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Source
Therapeutics: New drugs hit the target
Jana Schlütter
Nature 474,S5–S7(09 June 2011) doi:10.1038/474S5a Published online 08 June 2011
With two recently approved drugs and dozens more in the pipeline, hepatitis C treatment will improve over the next decade.
When Charles Gore talks about some of his colleagues, there is more than a hint of urgency in his voice. Although he cleared his hepatitis C virus (HCV) infection after receiving the standard treatment, two of his staff at the World Hepatitis Alliance, an advocacy organization, recently had liver transplants. “And they are lucky,” says Gore, who is president of the alliance. “This treatment does not help about 50% of the patients who are infected with the most common form of the virus. So their liver becomes worse, and many of them cannot get a transplant. They are facing death.”
Around the globe, patients who have not been cured by the current treatment, a combination of interferon-α and ribavirin, are waiting for new drugs. So far, their doctors have had nothing to offer them but another 48-week-round of the same drug combination, which had its last upgrade in 2001 when researchers attached a molecule called polyethylene glycol to interferon-α. This 'pegylation' allows interferon-α to stay in the body much longer, reducing the frequency of injections from three per week to one. But the side effects are just as harsh, including flu-like symptoms, anaemia and depression. And although the patient being treated may be too weak to work or enjoy family life, the virus often manages to survive and prosper under these conditions. At most, 20% of patients are cured by this second course of treatment. Still, there was no alternative.
This situation is about to change. Two powerful weapons against chronic HCV infection have been licensed: the protease inhibitors telaprevir, from Vertex Pharmaceuticals, based in Cambridge, Massachusetts, and boceprevir, from drug company Merck, headquartered in Whitehouse Station, New Jersey. When either drug is added to the current therapy, the cure rate increases for patients who have so far been spared the daunting year-long treatment: that is, 'treatment-naive' patients. The drugs also offer hope to those increasingly desperate patients who have not been helped by the standard treatment: instead of around a 20% chance of a cure, these 'treatment-experienced' patients now have a 30–90% chance. “We are approaching a new era of management of this disease,” says Mark Thursz, a hepatologist at Imperial College London and current secretary-general of the European Association for the Study of the Liver (EASL).
The drug manufacturers have tailored these protease inhibitors to HCV genotype 1, one of at least six forms of HCV. Genotype 1 is particularly widespread in the United States and Europe and is one of the least responsive to the standard treatment. The clinical studies coming out now, Thursz says, “show that the new drugs can tame the pit bull terriers of the hepatitis C world: the genotype 1 viruses.”
In addition to telaprevir and boceprevir, there are dozens of compounds in the pipeline, and that's only counting the ones that drug manufacturers are willing to disclose. These drugs target many aspects of the virus's life cycle — the stages it goes through in the liver cell to reproduce itself. Used in combination, the new agents might be able to target all HCV genotypes at once, while improving the cure rate and preventing drug resistance from emerging. Although most of these drug candidates are being added to the current treatment, an interferon-free regimen has recently shown promise — a possibility that could substantially reduce treatment side effects and increase adherence.
Direct hits
In the current regimen, interferon-α boosts the patient's immune system, and ribavirin is a general inhibitor of virus replication. By contrast, the new drugs target HCV directly. Telaprevir and boceprevir block HCV's NS3/4A protease. After an HCV particle attaches to and enters a liver cell, it releases its RNA, which is subsequently translated into a single polyprotein (see 'The life of HCV'). This long chain is cleaved into functional proteins by NS3/4A, which acts like a pair of molecular scissors. Without the protease, functional viral enzymes and structural proteins are not generated, so HCV cannot complete its life cycle.
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Nature 474,S5–S7(09 June 2011) doi:10.1038/474S5a Published online 08 June 2011
With two recently approved drugs and dozens more in the pipeline, hepatitis C treatment will improve over the next decade.
When Charles Gore talks about some of his colleagues, there is more than a hint of urgency in his voice. Although he cleared his hepatitis C virus (HCV) infection after receiving the standard treatment, two of his staff at the World Hepatitis Alliance, an advocacy organization, recently had liver transplants. “And they are lucky,” says Gore, who is president of the alliance. “This treatment does not help about 50% of the patients who are infected with the most common form of the virus. So their liver becomes worse, and many of them cannot get a transplant. They are facing death.”
Around the globe, patients who have not been cured by the current treatment, a combination of interferon-α and ribavirin, are waiting for new drugs. So far, their doctors have had nothing to offer them but another 48-week-round of the same drug combination, which had its last upgrade in 2001 when researchers attached a molecule called polyethylene glycol to interferon-α. This 'pegylation' allows interferon-α to stay in the body much longer, reducing the frequency of injections from three per week to one. But the side effects are just as harsh, including flu-like symptoms, anaemia and depression. And although the patient being treated may be too weak to work or enjoy family life, the virus often manages to survive and prosper under these conditions. At most, 20% of patients are cured by this second course of treatment. Still, there was no alternative.
This situation is about to change. Two powerful weapons against chronic HCV infection have been licensed: the protease inhibitors telaprevir, from Vertex Pharmaceuticals, based in Cambridge, Massachusetts, and boceprevir, from drug company Merck, headquartered in Whitehouse Station, New Jersey. When either drug is added to the current therapy, the cure rate increases for patients who have so far been spared the daunting year-long treatment: that is, 'treatment-naive' patients. The drugs also offer hope to those increasingly desperate patients who have not been helped by the standard treatment: instead of around a 20% chance of a cure, these 'treatment-experienced' patients now have a 30–90% chance. “We are approaching a new era of management of this disease,” says Mark Thursz, a hepatologist at Imperial College London and current secretary-general of the European Association for the Study of the Liver (EASL).
The drug manufacturers have tailored these protease inhibitors to HCV genotype 1, one of at least six forms of HCV. Genotype 1 is particularly widespread in the United States and Europe and is one of the least responsive to the standard treatment. The clinical studies coming out now, Thursz says, “show that the new drugs can tame the pit bull terriers of the hepatitis C world: the genotype 1 viruses.”
In addition to telaprevir and boceprevir, there are dozens of compounds in the pipeline, and that's only counting the ones that drug manufacturers are willing to disclose. These drugs target many aspects of the virus's life cycle — the stages it goes through in the liver cell to reproduce itself. Used in combination, the new agents might be able to target all HCV genotypes at once, while improving the cure rate and preventing drug resistance from emerging. Although most of these drug candidates are being added to the current treatment, an interferon-free regimen has recently shown promise — a possibility that could substantially reduce treatment side effects and increase adherence.
Direct hits
In the current regimen, interferon-α boosts the patient's immune system, and ribavirin is a general inhibitor of virus replication. By contrast, the new drugs target HCV directly. Telaprevir and boceprevir block HCV's NS3/4A protease. After an HCV particle attaches to and enters a liver cell, it releases its RNA, which is subsequently translated into a single polyprotein (see 'The life of HCV'). This long chain is cleaved into functional proteins by NS3/4A, which acts like a pair of molecular scissors. Without the protease, functional viral enzymes and structural proteins are not generated, so HCV cannot complete its life cycle.
SOURCE: CIESEK, S. & MANNS, M. P. NAT. REV. GASTROENTEROL. HEPATOL. 8, 69–71 (2011).
This March, the drug companies reported results of phase III clinical trials of telaprevir and boceprevir, each coupled with the current therapy, at EASL's International Liver Congress in Berlin. Two-thirds to three-quarters of treatment-naive patients with HCV genotype 1 are likely to clear the virus permanently. And treatment time is expected to be halved for patients in this group who have undetectable levels of virus after four weeks of treatment.
More hotly anticipated were the data for the treatment-experienced patients, including relapsers, whose virus had become undetectable but rebounded after their previous treatment ended; partial responders, whose viral load decreased by at least 99% but never became undetectable; and null responders, who previously had little success in fighting the virus. Telaprevir was tested in the Realize trial, which involved 662 patients from Europe and the United States. Adding telaprevir for 12 weeks to a 48-week-treatment course increased the cure rates from 24% to as high as 88% in relapsers, from 15% to 59% in partial responders, and from 5% to 33% in null responders. Boceprevir was tested in 403 patients in centres across the United States and Europe in the Respond-2 trial. Adding boceprevir for 32–44 weeks caused the cure rate to climb from 29% to 69-75% in relapsers and from 7% to 40-52% in partial responders. (Null-responders did not participate in this trial.)
“To have direct-acting antivirals against hepatitis C and to see such increases in cure rates is a huge step forward,” says Stefan Zeuzem, a hepatologist at the Goethe University Medical Center in Frankfurt, Germany, who was involved in both the Realize and Respond-2 trials. But these drugs are not cheap. “Cost will be a major issue,” he says. “However, we are preventing liver cancer and other end-stage liver diseases, which makes it worthwhile. We are aiming for a cure, not just a few more weeks to live.”
Both of these drugs also have side effects. More than half of the patients treated with telaprevir developed a rash, with 3–6% having a rash severe enough to halt treatment. Boceprevir is associated with anaemia (similarly to telaprevir) and can cause a metallic taste in the mouth, both of which affect nearly half of all patients. These problems are in addition to those caused by interferon-α and ribavirin, meaning that nearly every patient in the clinical trials suffered from at least one side effect. “It's still a tough treatment,” says Gore. “For patients, it's very important that clinicians manage these side effects well.”
If side effects cause patients to abandon treatment on the new regimen, this could lead to HCV developing resistance to the new drugs. The new protease inhibitors cannot be given alone and must be given with interferon-α and ribavirin to prevent protease-inhibitor resistance emerging. Thursz adds that as boceprevir and telaprevir are similar compounds, resistance to one will probably translate into resistance to the other (so-called cross-resistance), restricting future treatment options.
HCV is a highly mutation-prone virus, with many genetic variants present in any one host. Before treatment starts, variants that are resistant to a particular drug make up a minority of the viral population. Under selective pressure of the antivirals, however, these variants could become the dominant strains. “We understand resistance and have to manage it,” says Jean-Michel Pawlotsky, a hepatitis specialist at the University of East Paris in Créteil, France, and director of the French National Reference Center for Viral Hepatitis B, C and delta. He recommends that these new drugs should be administered at expert centres that can monitor resistance issues: “It is better to be well-treated than just treated,” he says.
Despite the high cure rates, not every HCV-infected patient will benefit from the new drugs. Possible drug–drug interactions are not yet fully understood. And there are no data for the many patients who are co-infected with HIV or for patients with end-stage renal disease, decompensated (or extremely advanced) liver cirrhosis or a recent liver transplant. Furthermore, telaprevir and boceprevir have been licensed by the US Food and Drug Administration only for treating HCV genotype 1 infection. As Pawlotsky says, “What we are seeing now is just the first step into the era of direct-acting antivirals. It will cause a real shift, but it's not a full revolution.”
Covering every angle
More than 50 other drugs are, however, in the research and development pipeline (see 'Drug candidates for treating HCV infection 2011'). Many of these are in new classes — that is, they target different mechanisms — and can be combined to create antiviral cocktails, limiting the emergence of drug resistance. With so many new agents snapping at their heels, boceprevir and telaprevir might have a very limited time as the dominant new drugs, says Zeuzem.
Two other first-generation protease inhibitors are in phase III trials: TMC435, from Tibotec Pharmaceuticals, in Beerse, Belgium, and pharmaceutical company Medivir in Huddinge, Sweden; and BI201335, from pharmaceutical company Boehringer Ingelheim, headquartered in Ingelheim am Rhein, Germany. Both are taken once daily instead of three times, seem to cause fewer side effects and might even be more potent than boceprevir and telaprevir.
The second generation of protease inhibitors is expected to be led by Merck's MK-5172, a compound that does not seem to have cross-resistance issues with other drugs of this class and might be effective across multiple genotypes. “We want to see if the resistance profile is robust enough that we can treat people who are failures from earlier generations of protease inhibitors,” says Keith Gottesdiener, vice president for hepatitis C clinical development at Merck. “That would be exciting if it was proven in the clinic.”
The pharmaceutical company F. Hoffmann-La Roche, headquartered in Basel, is about to start phase III trials of mericitabine, which blocks the activity of HCV's polymerase enzyme, NS5B. By mimicking the building blocks of RNA, mericitabine is incorporated into newly formed viral RNA but prematurely terminates it, halting the life cycle.
Another protein generating immense interest as a drug target is NS5A. Its precise function is mysterious, but it seems to be involved in the replication, assembly and release of HCV. BMS-790052, from biopharmaceutical company Bristol-Myers Squibb, headquartered in New York, was the first inhibitor in this class and is now in phase II trials. The pipeline is rapidly filling with others.
Cyclophilin A inhibitors block a host protein that is essential for viral replication. Candidates include alisporivir (DEB025), from drug company Novartis, headquartered in Basel, Switzerland, which is in phase III trials. In theory, targeting a human protein that HCV needs will render the virus' genotype or mutation status irrelevant and make it much less likely that resistant strains of HCV will emerge.
Free from interferon
There is also hope for patients who are not responsive to — or cannot tolerate — the backbone of triple therapy: interferon. This April at the International Liver Congress, Anna Lok, a hepatologist at the University of Michigan in Ann Arbor, presented data from a small phase IIa study of an interferon-free regimen in null responders. The study comprised patients on double therapy consisting of two classes of direct-acting antiviral: Bristol-Myers Squibb's BMS-650032 (a protease inhibitor) and BMS-790052 (an NS5A inhibitor). These patients were compared with a cohort taking quadruple therapy, consisting of these two antivirals plus interferon-α and ribavirin. The quadruple therapy suppressed HCV in 10 out of 10 patients for at least 12 weeks after treatment, whereas the interferon-free double therapy suppressed HCV in 4 out of 11 patients, with 6 being null or partial responders.
The numbers might not seem great, but they are a start. “The potential for an interferon-free regimen is some of the most exciting news this year,” says Thursz. Without interferon-α and ribavirin, the virus was expected to rebound after treatment, but this occurred in only one case. “There is still a lot of work to be done. But this was a group of very difficult-to-treat patients with excellent outcomes. Although the numbers are small, I think this is the direction we can expect to go in the future.”
Indeed, this possibility has energized hepatitis C researchers. “People would have laughed at you if you suggested something like this five years ago,” says Zeuzem. “Now, we know that such a therapy might be available in another five to ten years.”
Many of the other drugs in the pipeline, such as the NS5B inhibitors, could also be candidates for an interferon-free regimen, says Paul Pockros, co-director of clinical research at the Scripps Translational Science Institute in La Jolla, California, who is involved in phase II studies of mericitabine. Although mericitabine is slightly less effective than the protease inhibitors, it seems to be a safe drug with a high barrier to resistance. “This one would be a good partner for a protease inhibitor,” says Pockros.
With all the excitement about new drugs, one would be forgiven for thinking that interferon has had its day. But there is also development on this front. Bristol-Myers Squibb has developed a variant called pegylated interferon-λ, which is designed to be more potent and safer than interferon-α. Interferon-λ docks with different receptors that are less common than the receptors for interferon-α. This interferon circumvents the bone marrow and therefore avoids anaemia and flu-like symptoms, so it might be a good partner for direct-acting antivirals. “This would help a lot of people who cannot tolerate the current interferon,” says Zeuzem, who is involved in clinical trials of this drug.
With interferon-free regimens on the horizon, the question is whether a new interferon will be needed. But there are many potential pitfalls on the way to the clinic, and HCV is a very difficult virus to target. Researchers need as many options at their disposal as possible, says Zeuzem, “just in case.”
Needle-Exchange Programs Limit Spread of Hepatitis C
By Amy Norton
NEW YORK (Reuters Health) Jun 29 - Programs that give drug users clean needles or safer drug substitutes can cut the spread of hepatitis C, a new study suggests.
In the U.S., most of the roughly 18,000 new infections each year occur when drug users share tainted needles or syringes. Studies have found that clean-needle programs reduce needle-sharing and seem to protect against infection with HIV. The same appears true of programs that get addicts into treatment with methadone.
There has been little evidence that these programs help cut the spread of hepatitis C. But the new findings, published online May 25th in Addiction, suggest that needle and opiate-substitution programs can make a difference in hepatitis C risk, according to senior researcher Matthew Hickman at the University of Bristol in the UK.
Combining the results from six previous studies of UK programs, Hickman's team found that drug users with the highest "coverage" from clean-needle programs were about half as likely to acquire HCV infection as other users.
Among users who said they got enough clean needles to cover all of their injections, just under 4% became HCV-positive. That compared with 7% of drug users who didn't get clean needles for all their injections.
Similarly, the rate of new hepatitis C infection was 3% among drug users who were currently taking an opiate substitute (usually oral methadone), versus 7% among those not on treatment.
Drug users participating in both types of programs fared best of all, with a new infection rate of 2%.
"The implication is that hepatitis C transmission can be reduced by opiate substitution therapy and needle and syringe programs, especially their combination," Hickman told Reuters Health in an email.
While the study looked only at UK programs, it's likely the results would be similar in other countries, he said.
The study has its limits. Its findings are based on observational studies and small numbers. The researchers had usable information on 919 program participants across the six study sites, and there were 40 cases of new hepatitis C infection.
Still, Hickman said the study starts to fill a gap in the knowledge of how well injection drug use programs are working.
SOURCE: http://bit.ly/lMvRUW
Addiction 2011.
Source
Also See: Programs may curb hepatitis C in drug users
NEW YORK (Reuters Health) Jun 29 - Programs that give drug users clean needles or safer drug substitutes can cut the spread of hepatitis C, a new study suggests.
In the U.S., most of the roughly 18,000 new infections each year occur when drug users share tainted needles or syringes. Studies have found that clean-needle programs reduce needle-sharing and seem to protect against infection with HIV. The same appears true of programs that get addicts into treatment with methadone.
There has been little evidence that these programs help cut the spread of hepatitis C. But the new findings, published online May 25th in Addiction, suggest that needle and opiate-substitution programs can make a difference in hepatitis C risk, according to senior researcher Matthew Hickman at the University of Bristol in the UK.
Combining the results from six previous studies of UK programs, Hickman's team found that drug users with the highest "coverage" from clean-needle programs were about half as likely to acquire HCV infection as other users.
Among users who said they got enough clean needles to cover all of their injections, just under 4% became HCV-positive. That compared with 7% of drug users who didn't get clean needles for all their injections.
Similarly, the rate of new hepatitis C infection was 3% among drug users who were currently taking an opiate substitute (usually oral methadone), versus 7% among those not on treatment.
Drug users participating in both types of programs fared best of all, with a new infection rate of 2%.
"The implication is that hepatitis C transmission can be reduced by opiate substitution therapy and needle and syringe programs, especially their combination," Hickman told Reuters Health in an email.
While the study looked only at UK programs, it's likely the results would be similar in other countries, he said.
The study has its limits. Its findings are based on observational studies and small numbers. The researchers had usable information on 919 program participants across the six study sites, and there were 40 cases of new hepatitis C infection.
Still, Hickman said the study starts to fill a gap in the knowledge of how well injection drug use programs are working.
SOURCE: http://bit.ly/lMvRUW
Addiction 2011.
Source
Also See: Programs may curb hepatitis C in drug users
Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report
Published on: 2011-07-03
Introduction: Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.Case presentationA 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2).
She had received anti-viral therapy with interferon -2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA.
Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT.
A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation.
Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later.
Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection.
Conclusions: A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient.
A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.
Author: Masaaki HidakaMitsuhisa TakatsukiAkihiko SoyamaHisamitsu MiyaakiTatsuki IchikawaKazuhiko NakaoTakashi KanematsuSusumu Eguchi
Credits/Source: Journal of Medical Case Reports 2011, 5:276
Source
Introduction: Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.Case presentationA 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2).
She had received anti-viral therapy with interferon -2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA.
Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT.
A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation.
Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later.
Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no de novo malignancy. Neither of the siblings has developed an HCV infection.
Conclusions: A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient.
A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.
Author: Masaaki HidakaMitsuhisa TakatsukiAkihiko SoyamaHisamitsu MiyaakiTatsuki IchikawaKazuhiko NakaoTakashi KanematsuSusumu Eguchi
Credits/Source: Journal of Medical Case Reports 2011, 5:276
Source
Genetic Variant Linked to Development of Liver Cancer in Hepatitis C Virus Carriers
Tokyo, July 4, 2011 - (JCN Newswire) - A genome-wide study by researchers at the RIKEN Center for Genomic Medicine, Hiroshima University Hospital and Sapporo-Kosei General Hospital has identified a genetic variant associated with the development of liver cancer in chronic hepatitis C virus carriers. The findings are based on a study of 3,312 Japanese individuals and appear in the journal Nature Genetics.
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide. The hepatitis C virus (HVC) is the main risk factor for HCC in many western countries and in Japan, where of the more than 30,000 deaths each year from HCC, 70% involve HVC.
To identify risk factors connecting HVC and HCC, the research group conducted a genome-wide study on a group of 3,312 Japanese individuals carrying the hepatitis C virus. Analyzing a total of 467,538 genetic markers (called single nucleotide polymorphisms or SNPs) in a group of 212 HCV carriers with HCC and 765 HCV carriers without HCC, the group uncovered one SNP associated with HCC risk, located on a gene called DEPDC5. The association was confirmed in an independent replication study on a population of 2335 HVC carriers, 710 with HCC and 1625 without HCC.
The significance of the findings was further highlighted when the researchers adjusted their results for gender, age and platelet count, revealing that among Japanese individuals with chronic HVC infection, the DEPDC5 SNP roughly doubles the odds of developing HCC.
While deepening our understanding of the mechanisms triggering HCC, the discovery of the DEPDC5 SNP locus also provides a valuable target for new therapy techniques, promising progress in the ongoing battle to overcome one of the world's most deadly cancers.
Reference:
Daiki Miki, Hidenori Ochi, C Nelson Hayes, Hiromi Abe, Tadahiko Yoshima, Hiroshi Aikata, Kenji Ikeda, Hiromitsu Kumada, Joji Toyota, Takashi Morizono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani & Kazuaki Chayama. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nature Genetics, doi:10.1038/ng.876.
About RIKEN Institute
RIKEN, one of Japan's leading research institutes, conducts basic and applied experimental research in a wide range of science and technology fields including physics, chemistry, medical science, biology and engineering. Initially established as a private research foundation in Tokyo in 1917, RIKEN became an independent administrative institution in 2003. For more information, visit www.riken.jp/engn/index.html.
Contact:
Kazuaki Chayama
Laboratory for Digestive Diseases
RIKEN Center for Genomic Medicine (CGM),
Tel: +81-82-257-5955
Fax: +81-82-257-1559
Ms. Tomoko Ikawa (PI officer)
Global Relations Office
RIKEN
Tel: +81-48-462-1225
Fax: +81-48-463-3687
Email: koho@riken.jp
Source
Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the third leading cancer-related cause of death and the seventh most common form of cancer worldwide. The hepatitis C virus (HVC) is the main risk factor for HCC in many western countries and in Japan, where of the more than 30,000 deaths each year from HCC, 70% involve HVC.
To identify risk factors connecting HVC and HCC, the research group conducted a genome-wide study on a group of 3,312 Japanese individuals carrying the hepatitis C virus. Analyzing a total of 467,538 genetic markers (called single nucleotide polymorphisms or SNPs) in a group of 212 HCV carriers with HCC and 765 HCV carriers without HCC, the group uncovered one SNP associated with HCC risk, located on a gene called DEPDC5. The association was confirmed in an independent replication study on a population of 2335 HVC carriers, 710 with HCC and 1625 without HCC.
The significance of the findings was further highlighted when the researchers adjusted their results for gender, age and platelet count, revealing that among Japanese individuals with chronic HVC infection, the DEPDC5 SNP roughly doubles the odds of developing HCC.
While deepening our understanding of the mechanisms triggering HCC, the discovery of the DEPDC5 SNP locus also provides a valuable target for new therapy techniques, promising progress in the ongoing battle to overcome one of the world's most deadly cancers.
Reference:
Daiki Miki, Hidenori Ochi, C Nelson Hayes, Hiromi Abe, Tadahiko Yoshima, Hiroshi Aikata, Kenji Ikeda, Hiromitsu Kumada, Joji Toyota, Takashi Morizono, Tatsuhiko Tsunoda, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani & Kazuaki Chayama. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nature Genetics, doi:10.1038/ng.876.
About RIKEN Institute
RIKEN, one of Japan's leading research institutes, conducts basic and applied experimental research in a wide range of science and technology fields including physics, chemistry, medical science, biology and engineering. Initially established as a private research foundation in Tokyo in 1917, RIKEN became an independent administrative institution in 2003. For more information, visit www.riken.jp/engn/index.html.
Contact:
Kazuaki Chayama
Laboratory for Digestive Diseases
RIKEN Center for Genomic Medicine (CGM),
Tel: +81-82-257-5955
Fax: +81-82-257-1559
Ms. Tomoko Ikawa (PI officer)
Global Relations Office
RIKEN
Tel: +81-48-462-1225
Fax: +81-48-463-3687
Email: koho@riken.jp
Source
Telaprevir Markedly Improves HCV Genotype 1 Cure Rates
Summary and Comment
Final results of phase III trials show that telaprevir plus standard therapy with peginterferon alfa-2a and ribavirin was more effective than standard therapy alone.
Recently, telaprevir-based triple therapy (i.e., in combination with peginterferon alfa-2a and ribavirin) was approved for the treatment of chronic hepatitis C virus (HCV) infection. The final results of the international phase III trials for both treatment-naive and treatment-experienced patients with HCV genotype 1 infection are now available.
In the first of two industry-sponsored, double-blind, placebo-controlled trials, 1095 treatment-naive patients were randomized to receive either triple therapy for 12 weeks followed by peginterferon plus ribavirin for 12 weeks — or 36 weeks if HCV RNA was detectable at weeks 4 or 12 — (T12PR group); triple therapy for 8 weeks followed by peginterferon plus ribavirin for either 16 or 36 weeks (T8PR group); or peginterferon plus ribavirin for 48 weeks (PR group).
In the second trial, 663 treatment-experienced patients were randomized 2:2:1 to receive either triple therapy for the first 12 weeks followed by 36 weeks of peginterferon plus ribavirin (T12PR48 group), a 4-week lead-in of peginterferon plus ribavirin followed by 12 weeks of triple therapy and then 32 weeks of peginterferon plus ribavirin (lead-in T12PR48 group), or peginterferon plus ribavirin for 48 weeks (PR48 group). In both trials, doses were 750 mg every 8 hours for telaprevir, 180 µg weekly for peginterferon alfa-2a, and 1000–1200 mg daily for ribavirin. The primary endpoint was sustained virologic response (SVR).
For treatment-naive patients, SVR rates were higher in the T12PR and T8PR groups than in the PR group — 75% and 69% versus 44%; P<0.001. Although the numbers of patients who were black or had advanced fibrosis were small in the study cohort (7% and 20%, respectively), in both subgroups, SVR rates were higher in the telaprevir groups than the peginterferon plus ribavirin group.
Among treatment-experienced patients, SVR rates for arms T12PR48, lead-in T12PR48, and PR48, respectively, were 83%, 88%, and 24% for previous relapse; 59%, 54%, and 15% for previous partial response; and 29%, 33%, and 5% for previous null response (P<0.001 for all comparisons). In general, virologic failure in the telaprevir groups was attributable primarily to the development of drug resistance. In both studies, the telaprevir groups had higher rates of anemia, rashes, pruritus, and gastrointestinal problems than the peginterferon plus ribavirin group. Discontinuation of medications for any reason ranged from 10% to 15% for the telaprevir regimens and from 7% to 10% for the peginterferon plus ribavirin regimen.
Comment: These companion studies demonstrate that telaprevir-based regimens are significantly more effective in HCV genotype 1–infected patients than peginterferon plus ribavirin alone — for both treatment-naive and treatment-experienced patients. Although more adverse events occurred in the telaprevir-treated groups, discontinuation rates were still relatively low. Overall, the best SVRs were seen in treatment-naive and prior-relapse patients (75%), followed by previous partial responders, treatment-naive blacks, and patients with advanced fibrosis (50%–60%), and last, previous null responders (30%). Therefore, caution should be exercised in treating null responders, especially since the majority of virologic failure leads to drug resistance.
— Atif Zaman, MD, MPH
Published in Journal Watch Gastroenterology July 1, 2011
Citation(s):
Jacobson IM et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011 Jun 23; 364:2405.
Medline abstract (Free)
Zeuzem S et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011 Jun 23; 364:2417.
Medline abstract (Free)
Final results of phase III trials show that telaprevir plus standard therapy with peginterferon alfa-2a and ribavirin was more effective than standard therapy alone.
Recently, telaprevir-based triple therapy (i.e., in combination with peginterferon alfa-2a and ribavirin) was approved for the treatment of chronic hepatitis C virus (HCV) infection. The final results of the international phase III trials for both treatment-naive and treatment-experienced patients with HCV genotype 1 infection are now available.
In the first of two industry-sponsored, double-blind, placebo-controlled trials, 1095 treatment-naive patients were randomized to receive either triple therapy for 12 weeks followed by peginterferon plus ribavirin for 12 weeks — or 36 weeks if HCV RNA was detectable at weeks 4 or 12 — (T12PR group); triple therapy for 8 weeks followed by peginterferon plus ribavirin for either 16 or 36 weeks (T8PR group); or peginterferon plus ribavirin for 48 weeks (PR group).
In the second trial, 663 treatment-experienced patients were randomized 2:2:1 to receive either triple therapy for the first 12 weeks followed by 36 weeks of peginterferon plus ribavirin (T12PR48 group), a 4-week lead-in of peginterferon plus ribavirin followed by 12 weeks of triple therapy and then 32 weeks of peginterferon plus ribavirin (lead-in T12PR48 group), or peginterferon plus ribavirin for 48 weeks (PR48 group). In both trials, doses were 750 mg every 8 hours for telaprevir, 180 µg weekly for peginterferon alfa-2a, and 1000–1200 mg daily for ribavirin. The primary endpoint was sustained virologic response (SVR).
For treatment-naive patients, SVR rates were higher in the T12PR and T8PR groups than in the PR group — 75% and 69% versus 44%; P<0.001. Although the numbers of patients who were black or had advanced fibrosis were small in the study cohort (7% and 20%, respectively), in both subgroups, SVR rates were higher in the telaprevir groups than the peginterferon plus ribavirin group.
Among treatment-experienced patients, SVR rates for arms T12PR48, lead-in T12PR48, and PR48, respectively, were 83%, 88%, and 24% for previous relapse; 59%, 54%, and 15% for previous partial response; and 29%, 33%, and 5% for previous null response (P<0.001 for all comparisons). In general, virologic failure in the telaprevir groups was attributable primarily to the development of drug resistance. In both studies, the telaprevir groups had higher rates of anemia, rashes, pruritus, and gastrointestinal problems than the peginterferon plus ribavirin group. Discontinuation of medications for any reason ranged from 10% to 15% for the telaprevir regimens and from 7% to 10% for the peginterferon plus ribavirin regimen.
Comment: These companion studies demonstrate that telaprevir-based regimens are significantly more effective in HCV genotype 1–infected patients than peginterferon plus ribavirin alone — for both treatment-naive and treatment-experienced patients. Although more adverse events occurred in the telaprevir-treated groups, discontinuation rates were still relatively low. Overall, the best SVRs were seen in treatment-naive and prior-relapse patients (75%), followed by previous partial responders, treatment-naive blacks, and patients with advanced fibrosis (50%–60%), and last, previous null responders (30%). Therefore, caution should be exercised in treating null responders, especially since the majority of virologic failure leads to drug resistance.
— Atif Zaman, MD, MPH
Published in Journal Watch Gastroenterology July 1, 2011
Citation(s):
Jacobson IM et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 2011 Jun 23; 364:2405.
Medline abstract (Free)
Zeuzem S et al. Telaprevir for retreatment of HCV infection. N Engl J Med 2011 Jun 23; 364:2417.
Medline abstract (Free)
Innovative vaccines with nanotechnology
Public release date: 1-Jul-2011
Contact: Dr. Bastian Dornbach
bastian.dornbach@helmholtz-hzi.de
49-531-618-11407
Helmholtz Association of German Research Centres
European Research Consortium wants to develop novel vaccination against hepatitis C
HCVAX is a European joint project that reaches out to develop a vaccine against hepatitis C based on nanotechnology. The German Helmholtz Centre for Infection Research (Helmholtz-Zentrum für Infektionsforschung, HZI) in Braunschweig and its department "Vaccinology and Applied Microbiology" is now a part of the transnational consortium with researchers from Germany, France and Switzerland.
More than 170 million people are infected with the hepatitis C virus (HCV) worldwide. Also in Europe this form of hepatitis is a big problem with three per cent of the population affected. The virus is transmitted in operations such as transplantations or by the re-use of syringes for drug usage. Anti-viral treatments are very expensive, have serious side effects and are only effective for some patients. Most of the patients carry the infection for the rest of their lives, with the threat of later developing liver cirrhosis and cancer. Certainly, the most effective way to combat hepatitis C would be a vaccine against the virus – but to date no efficacious vaccine exists.
"We will pursue a completely new approach to develop a HCV vaccine," says Prof. Carlos A. Guzmán, head of the Vaccinology Department at the HZI. With the help of innovative, biocompatible nanogels part of the genetic information of the virus is brought into the body by so-called "RNA replicons". The synthetic nanogels have a diameter of only a few nanometres and are composed of a biopolymer matrix. Immune cells will take up the nanogels with the genetic information and will produce harmless components of HCV. The immune cell then responds to those foreign structures and will generate memory cells: with this, the vaccination would be successful and from then on one would be protected against an infection with pathogen HCV.
By using novel drug amplifiers, so-called adjuvants, the immune response shall be more efficient and targeted. "The HZI has a long-standing expertise in this field. We will incorporate this knowledge into the project to develop more effective vaccines," says Guzmán. "We want to identify those adjuvants that are most eligible for a use in the nanogel composition. The targeted transport to certain defence cells shall guarantee an optimal immune response."
To exclude side effects, potential vaccine candidates have to be tested in several systems. Promising structures will then be selected for further clinical development.
The consortium consists of two companies, three academic institutions and one clinic. They combine their expertise on the field of nanotechnology, biochemistry, immunology, vaccine development and clinical research. "Beyond that we expect that these novel vaccination strategies can be expanded onto the clinical management of other diseases," says Guzmán.
Funding is granted for the next three years from the "EuroNanoMed Joint Transnational Initiative" of the European Union. The German Ministry for Research and Education is funding the project in Germany.
The Partners:
Federal Department of Economic Affairs (Eidgenössisches Volkswirtschaftsdepartement), Mittelhäusern, Switzerland (coordinator)
Medipol SA, Lausanne, Switzerland
Institut Pasteur, Paris, France
Helmholtz Centre for Infection Research (Helmholtz-Zentrum für Infektionsforschung GmbH), Braunschweig, Germany
EDI GmbH, Reutlingen, Germany
Hôpital Cochin, Paris, France
Source
Contact: Dr. Bastian Dornbach
bastian.dornbach@helmholtz-hzi.de
49-531-618-11407
Helmholtz Association of German Research Centres
European Research Consortium wants to develop novel vaccination against hepatitis C
HCVAX is a European joint project that reaches out to develop a vaccine against hepatitis C based on nanotechnology. The German Helmholtz Centre for Infection Research (Helmholtz-Zentrum für Infektionsforschung, HZI) in Braunschweig and its department "Vaccinology and Applied Microbiology" is now a part of the transnational consortium with researchers from Germany, France and Switzerland.
More than 170 million people are infected with the hepatitis C virus (HCV) worldwide. Also in Europe this form of hepatitis is a big problem with three per cent of the population affected. The virus is transmitted in operations such as transplantations or by the re-use of syringes for drug usage. Anti-viral treatments are very expensive, have serious side effects and are only effective for some patients. Most of the patients carry the infection for the rest of their lives, with the threat of later developing liver cirrhosis and cancer. Certainly, the most effective way to combat hepatitis C would be a vaccine against the virus – but to date no efficacious vaccine exists.
"We will pursue a completely new approach to develop a HCV vaccine," says Prof. Carlos A. Guzmán, head of the Vaccinology Department at the HZI. With the help of innovative, biocompatible nanogels part of the genetic information of the virus is brought into the body by so-called "RNA replicons". The synthetic nanogels have a diameter of only a few nanometres and are composed of a biopolymer matrix. Immune cells will take up the nanogels with the genetic information and will produce harmless components of HCV. The immune cell then responds to those foreign structures and will generate memory cells: with this, the vaccination would be successful and from then on one would be protected against an infection with pathogen HCV.
By using novel drug amplifiers, so-called adjuvants, the immune response shall be more efficient and targeted. "The HZI has a long-standing expertise in this field. We will incorporate this knowledge into the project to develop more effective vaccines," says Guzmán. "We want to identify those adjuvants that are most eligible for a use in the nanogel composition. The targeted transport to certain defence cells shall guarantee an optimal immune response."
To exclude side effects, potential vaccine candidates have to be tested in several systems. Promising structures will then be selected for further clinical development.
The consortium consists of two companies, three academic institutions and one clinic. They combine their expertise on the field of nanotechnology, biochemistry, immunology, vaccine development and clinical research. "Beyond that we expect that these novel vaccination strategies can be expanded onto the clinical management of other diseases," says Guzmán.
Funding is granted for the next three years from the "EuroNanoMed Joint Transnational Initiative" of the European Union. The German Ministry for Research and Education is funding the project in Germany.
The Partners:
Federal Department of Economic Affairs (Eidgenössisches Volkswirtschaftsdepartement), Mittelhäusern, Switzerland (coordinator)
Medipol SA, Lausanne, Switzerland
Institut Pasteur, Paris, France
Helmholtz Centre for Infection Research (Helmholtz-Zentrum für Infektionsforschung GmbH), Braunschweig, Germany
EDI GmbH, Reutlingen, Germany
Hôpital Cochin, Paris, France
Source
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