If HCV Treatment Relapse Occurs, It Occurs Quickly

Archives Online publication date: 1-May-2010.

People infected with both HIV and hepatitis C virus (HCV) who successfully complete 12 months of HCV treatment can experience relapse of their infection, but if they do, it usually happens within the first 12 weeks after therapy is stopped, say the authors of a study published in the November 1 issue of Clinical Infectious Diseases.The goal of HCV treatment is to maintain an undetectable HCV viral load for at least six months after completing a year’s course of therapy, called a sustained virologic response (SVR).

A number of studies have shown that SVRs are less likely for people coinfected with both HIV and HCV, compared with people infected with only HCV. In people infected with HIV and HCV genotypes 1 or 4—the toughest to treat—the likelihood of success is even lower. What isn’t well characterized, however, are the patterns in HIV- and HCV-coinfected people who relapse after treatment.

A relapse is when someone makes it to the end of treatment with an undetectable HCV level, but then has detectable virus again sometime during the next six months.To describe how often and when relapse occurs, José Medrano, MD, from the Hospital Carlos III in Madrid and his colleagues, examined the medical records of 616 HCV-infected people who received pegylated interferon and ribavirin treatment between 2001 and 2008.

Of the 616 people, 386 were coinfected with HIV and HCV.
 About 60 percent of those infected with only HCV made it to the end of the year’s worth of treatment with an undetectable HCV viral load, called an end-of-treatment response (ETR). Only 37 percent of coinfected people had an ETR. 
Of those who had an ETR, 22 percent of those infected with only HCV experienced an HCV relapse. Conversely, 33 percent of the HIV-positive individuals with an ETR experienced a relapse. Not surprisingly, relapse was more common in all those infected with HCV genotypes 1 or 4.

HCV treatment relapses occurred almost always within the first 12 weeks after a person completed their HCV treatment regimen, regardless of whether they were coinfected or had only HCV. In the three patients who experienced HCV viral load rebounds more than 12 weeks after achieving an ETR, researchers suspect that reinfection—not a relapse of previous HCV infection—was to blame in two cases. 


The authors state that better understanding treatment relapse, particularly in people coinfected with HIV and HCV, gives both providers and patients a better sense of what to expect during—and the weeks following—HCV treatment.

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Hepatitis B PCR-based molecular diagnostic solution

Novel molecular diagnostics solutions meet demand for fast, accurate testing

The first real-time tests for tuberculosis and drug resistant tuberculosis and a way to measure the viral load or amount of hepatitis B virus in a blood sample are among the advances in molecular diagnostic technology. Sean Ottewell reports.
The emergence and spread of drug-resistant mycobacterium tuberculosis (TB) threatens global TB control efforts, and there is an urgent need for new diagnostic tests that rapidly identify drug sensitivity profiles of TB strains.

To help address these concerns, Seegene has introduced Anyplex MDR-TB screening test, which it says is the first real-time PCR molecular diagnostic capable of simultaneous detection of TB and genetic mutations leading to multi-drug resistant TB (MDR-TB) within four hours.
According to the World Health Organisation (WHO), TB strains that are resistant to all major anti-TB drugs have been documented in every country by the non-governmental organisation recent survey. A particularly dangerous form of drug-resistant TB is multi-drug resistant TB (MDR-TB), which is defined as the disease caused by TB bacilli resistant to, among others, the two most powerful anti-TB drugs, isoniazid (INH) and rifampicin (Rif).The rate for successful MDR-TB treatment is extremely low and the progress of the disease is faster than normal TB, resulting in 40-50 per cent of mortality rate. Rates of MDR-TB are troublingly high in some countries, especially in the former Soviet Union, and threaten TB infectious disease control efforts. WHO estimates that more than 440 000 people are infected with MDR-TB.
Using Anyplex MDR-TB screening test, healthcare workers will be able to quickly determine whether or not a patient is infected with a strain of TB that is resistant to INH and Rif. The Anyplex MDR-TB is a real-time detection test of M. tuberculosis that quickly and comprehensively determines the levels of targets in a patient's various sample types, and identifies mutations of drug resistant genes to better inform a diagnosis.
Because genetic mutations that lead to antibiotic resistance are minute and sit close together, so far conventional PCR or conventional real-time PCR tests are not able to discriminate these mutations accurately within the same test procedure. In contrast, the Anyplex MDR-TB test can detect the mutations of drug resistant genes to Rif (rpoB: D516V/Y, H526D/Y, S531L) and INH (katG: S315T (2 cases); inhA promoter: -15(C/T)).
According to Seegene, the unprecedented speed and accuracy of the Anyplex MDR-TB tests will enable doctors and clinicians to quickly provide an appropriate treatment to prevent the spread of MDR-TB.

Seegene's new MDR-TB test takes TB diagnostics to a new level. Current TB test methods are hindered by speed (culture typically required 2-8 weeks for results), low sensitivity (acid-fast bacilli smear microscopy produced results in 24 hours but at the cost of missing a significant portion of TB cases) and low specificity (culture and microscopy methods not being able to efficiently differentiate between M. tuberculosis and non-tuberculosis mycobacteria). Furthermore, none of these approaches are able to rapidly and efficiently identify a patient's resistance to the major drugs for treating TB - INH and Rif. Even if sequencing and line probe assay are available to test drug resistance, the procedures are quite complicated and time-consuming.

"Making a fast and accurate diagnosis of the type of TB infection a patient may have is the most important step to curing a patient. Because MDR-TB is difficult to treat, preventing its spread throughout the population is essential. The Anyplex MDR-TB test is a powerful new tool that healthcare workers can use to rapidly determine MDR-TB infections, which will both help stop it from spreading and allow health care professionals to set a course of alternative medications for infected patients," said Jong-Yoon Chun, chief executive officer of Seegene.
Molecular testing

QIAGEN has also launched a novel, automated PCR-based molecular diagnostic solution. Called QIAsymphony RGQ, the company says it sets new standards for molecular testing and incorporates all workflow steps from sample to detection. It offers many features which create exceptional flexibility, such as continuous loading, random access, open channels for user-developed tests, the broadest menu of commercial assays as well as the ability to process an almost unlimited range of sample types. This, says the company, provides laboratories with a system that transforms their work in the emerging field of molecular diagnostics (Fig. 1).
Data integration

This new solution is comprised of modules that can be used as standalone systems or combined into a fully integrated system. The QIAsymphony RGQ system comprises the physical and data integration of the modules QIAsymphony SP for sample preparation, QIAsymphony AS for assay setup, and the Rotor-Gene Q real time PCR thermocycler. QIAsymphony also provides the broadest available PCR-based assay menu, including the artus real time PCR kits for the detection of HIV, HCV, HBV, and a transplantation panel with CMV, EBV, HSV, VZV and BKV.
A large pipeline of further tests will be launched in the coming months, including therascreen EGFR, KRAS, as well as artus Influenza, CT, CT/Ng and an extended transplantation panel. Many more tests are in development as well as the ability to integrate detection options such as pyrosequencing, and multiplexing solutions.
"Our new integrated and validated QIAsymphony RGQ system has been developed to meet the testing needs of molecular diagnostic laboratories now and in the future", said Peer Schatz, QIAGEN's ceo.

Micronics has announced that the US Department of Defence has awarded the company a US$2.6m applied research and technology development award under the US Army medical research and material command's polytrauma and blast injury project for advancement of its PanNAT system for point-of-care molecular diagnosis of infectious pathogens.
The armed forces are interested in innovative medical technology to develop a highly accurate, rapid assay device for detecting bloodborne pathogens. The device needed would have a higher degree of sensitivity than existing equipment, and provide instant results, while being durable and fully functional in field testing to withstand wartime conditions.
In response, the Micronics says that PanNAT technology represents a significant advance over current nucleic acid-based assay systems, which are complex, expensive and can take several hours or days. PanNAT system is a sample-to-answer device that is easy to use; the lightweight, portable instrument processes a cartridge into which all reagents are incorporated for rapid disease detection.

The award will advance the development of assays on the compact, WiFi-enabled, mains and/or battery-powered PanNAT instrument for the direct detection of multiple bloodborne pathogens in fresh blood samples. The specific pathogens to be detected are those for hepatitis B and C (HBV, HCV) as well as the human immunodeficiency virus (HIV). The assay is intended for use in the battlefield to screen out any infectious blood donated for transfusion.
Measuring viral load

Meanwhile Abbott has received approval from the US Food and Drug Administration (FDA) to market the RealTime HBV assay for measuring viral load or the amount of hepatitis B virus (HBV) in a patient's blood. It is the first and only approved test capable of automating HBV viral load testing from sample extraction to final results. The assay is intended for use as an aid in the management of patients with chronic HBV infection undergoing anti-viral therapy. It can be used to measure HBV DNA levels at baseline and during treatment to aid in assessing response to treatment. Assay results must be interpreted within the context of all relevant clinical and lab findings. Use of the assay to determine the clinical stage of HBV infection has not been established. Clinical performance characteristics have been established for individuals treated with adefovir dipivoxil. The assay is not intended as a screening test for HBV or as a diagnostic test for confirming the presence of HBV infection.

"The Abbott RealTime HBV assay, which is the first and only automated HBV viral load test approved by the FDA, is an important tool for helping physicians make and adjust treatment decisions for newly-diagnosed patients and those taking anti-viral medications," said Stafford O'Kelly, head of Abbott's molecular diagnostics business. "The test will also help improve laboratory productivity by automating the most labour intensive steps of HBV testing."
Abbott's molecular HBV assay detects and measures all known HBV genotypes (A-H) by targeting an essential, highly conserved segment of the HBV genome. The capability for detecting HBV genotypes is important for both monitoring the disease and guiding treatment decisions.

FG-2216 New Drug To Treat Anemia in dialysis patients

New Drug To Treat Anemia

(Ivanhoe Newswire) -- The name of the drug is FG-2216, and it’s designed to stimulate production of the hormone erythropoietin (EPO) in dialysis patients. In fact, it’s the world’s first oral drug for the treatment of kidney disease-related anemia; it’s a hypoxia inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stabilizes the "master switch," which normally tells the body to produce EPO in response to low oxygen levels.

Anemia, one of the more common blood disorders, is caused by low production of EPO, which has been assumed to result from damage to the kidney cells that produce EPO.

"Our study clearly shows that this may not be the case, and that the kidneys of patients on dialysis retain significant ability to produce erythropoietin," which Wanja M. Bernhardt, MD, Department of Nephrology, University hospital Erlangen, Germany, was quoted as saying. "Renal anemia seems to result from disturbed regulation rather than lost production capacity of the hormone.

Treatment with FG-2216 considerably increased EPO production in dialysis patients, in addition to healthy people with normal kidneys. The utmost increase in EPO production occurred in dialysis patients whose kidneys were still present, but no longer functioning.

FG-2216 additionally stimulated EPO production in dialysis patients with no kidneys. These are individuals whose kidneys had been removed at surgery for cancer or other diseases. The significant increase in EPO production in patients devoid of kidneys was approximately as high as in people with normally functioning kidneys. In patients with no kidneys, FG-2216 in fact stimulated production of EPO by the liver.

The study’s outcome questions the standard knowledge that dialysis-related anemia occurs for the reason that patients with advanced kidney disease can no longer make their own EPO. "Our results confirm that both the liver and the kidneys retain a significant production capacity for erythropoietin in end-stage renal disease patients," adds Bernhardt.

Presently, patients with dialysis-related anemia are given EPO replacement therapy with drugs called erythropoiesis-stimulating agents (ESAs). Regardless of nearly two decades of use, there remains a constant debate related to the safety, appropriate clinical use, and in due course high costs of ESAs. If the latest results are borne out by future studies, then use of prolyl-hydroxylase inhibitors – such as FG-2216 to help the body make its own EPO – might provide a new-fangled alternative to ESAs.

The groundwork has been set with this study, which moreover evaluated merely the response to a single dose of FG-2216. Although there were no harmful effects, the results and long-term safety of activation of HIF by prolyl-hydroxylase inhibitors remain uncertain. Additional research will furthermore be required to find out why HIF is evidently not stabilized in response to decreased oxygen concentrations in patients with kidney disease but responds to treatment with prolyl-hydroxylase inhibitors.

SOURCE: Journal of the American Society of Nephrology, November 29, 2010

Hepatitis C News: FDA Approves Merit Phase 3 clinical trial protocol to treat primary liver cancer

FDA Approves Merit Medical's HiQuality Clinical Trial Protocol for the Treatment of Primary Liver Cancer

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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.

QuadraSphere is indicated for embolization of hypervascular tumors and peripheral arteriovenous malformations. The identical product marketed in Europe as HepaSphere Microspheres(TM) has been CE-marked in the European Union since 2007 for embolization of HCC and hepatic metastases, with or without delivery of doxorubicin.
"I am extremely pleased with the efforts of our BioSphere Regulatory and Medical Affairs Department headed by Dr. Melodie R. Domurad, PhD," said Fred P. Lampropoulos, Merit's Chairman and Chief Executive Officer. "We are very excited about the initiation of this important study."

Merit Medical is a leading manufacturer and marketer of proprietary disposable devices used primarily in cardiology, radiology and endoscopy. It has recently added the BioSphere microsphere products to its line of tumor treatment options.

The phase 3 study is a prospective, randomized, blinded and controlled investigation of HepaSphere/QuadraSphere Microspheres for delivery of doxorubicin for the treatment of hepatocellular cancer.

Known as the HiQuality Study (HepaSphere/QuadraSphere in Liver Cancer Treatment), the primary endpoint of the clinical trial is survival. Secondary endpoints include tumor response by mRECIST criteria, safety, resource utilization such as length of hospitalization, and adverse events. The study will enroll 500 patients and be conducted in approximately 20 clinical sites in the U.S., Europe, and South America.

Dr. Riccardo Lencioni, who developed the guidelines for image acquisition and interpretation for the trial stated, "This study meets the highest standards for clinical research in hepatocellular carcinoma, as recommended in Design and Endpoints of Clinical Trials in Hepatocellular Carcinoma, guidelines for clinical research in HCC by an expert panel convened by the American Association for the Study of Liver Disease, and published in the Journal of the National Cancer Institute. The design of the investigation is rigorous, and has been extensively reviewed by the FDA."

Dr. Lencioni, M.D., Associate Professor of Radiology at the University of Pisa in Italy and Director of the Division of Diagnostic Imaging and Intervention at the Department of Hepatology and Liver Transplantation at the Pisa University Hospital, will be overseeing the central imaging review and evaluation of tumor response. Professor Lencioni is Chairman of the Membership Committee and a member of the Executive Committee of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and Chairman of the Programme Committee of the European Conference on Interventional Oncology (ECIO).

He is also a member of the Steering Committee of the World Conference on Interventional Oncology (WCIO). Professor Lencioni has been one of the founders of the International Liver Cancer Association (ILCA), and is a member of the Governing Board. Professor Lencioni has received more than 40 international awards; authored 134 articles or editorials; and is the editor of seven books. Professor Lencioni has served on the editorial board of Cardiovascular and Interventional Radiology, Investigative Radiology, European Radiology, Journal of Hepatology, Journal of Interventional Oncology, and La Radiologia Medica.

Michael Soulen, M.D. from the University of Pennsylvania Medical Center and Professor of Radiology specializing in Interventional Radiology, will direct the study as principal investigator. Active in the Society of Interventional Radiology (SIR), Dr. Soulen has served on the Executive Council, chaired the 1999 Annual Scientific Meeting, and acted as Director of Research Education for the SIR Foundation. He also serves on committees of the Radiological Society of North America (RSNA) and the American College of Radiology (ACR). Dr. Soulen chairs the steering committee of the World Conference of Interventional Oncology (WCIO). He is also an editorial board member and/or reviewer for numerous publications, including the Journal of Vascular and Interventional Radiology. He has published nearly100 peer-reviewed articles and more than 50 editorials, chapters and invited manuscripts.

About Liver Cancer
Liver cancer is the third leading cause of cancer deaths worldwide. The sharp rise in hepatitis C infections, alcohol consumption and obesity are reported as key contributing factors to the increase in liver cirrhosis and liver cancer. Liver transplantation or tumor resection is considered potentially a curative treatment; however, only about 25 percent of liver cancers are diagnosed when they can be treated surgically.

Surgical removal is not possible for more than two-thirds of primary liver cancer patients and 90 percent of patients with secondary liver cancer. According to the U.S. National Cancer Institute (NCI), no standard treatment currently exists for liver cancer when tumors cannot be surgically removed and liver transplantation is not a viable option. However, both the NCI and the Society of Interventional Radiologists (SIR) report that transarterial chemoembolization (TACE) has shown promising results.

hqTACE - Merit Advances Chemoembolization
Drug-eluting embolization treats hepatocellular carcinoma through the dual action of delivering chemotherapy into the tumors while also cutting off the blood supply that supports them. QuadraSphere adds two benefits to embolization therapy. First, by ionically binding the doxorubicin throughout the microspheres and eluting it into the cancer in a sustained manner, more drug can be delivered into the tumor, with less escaping into peripheral circulation. Complementary to the targeted delivery, QuadraSphere Microspheres have a unique formulation that makes them highly compressible and conformable, so they mold to the vessel lumen, creating both excellent contact with the vessel walls for delivery of chemotherapy and very efficient occlusion of the vessels feeding the tumor. Initial clinical results have demonstrated improved safety and reduced adverse events compared to treatment by conventional chemoembolization.

About Conventional Transarterial Chemoembolization (cTACE)
Conventional transarterial chemoembolization (cTACE) is a two-stage process involving the injection of chemotherapeutic drugs, typically emulsified with iodized oil, directly into the blood vessels that feed a tumor. The drug is followed by the delivery of an embolic agent used as a plug to block the tumor's blood supply and temporarily retain the cytotoxic drugs in place. However, the occlusion is limited in area and some of the chemotherapy still escapes into circulation, which leads to adverse effects.

Continue Reading http://www.globenewswire.com/newsroom/prs/?pkgid=3282

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Apricus, FDA agree on liver cancer drug study
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.

Apricus is testing a drug candidate called PrevOnco as a treatment for advanced, inoperable liver cancer. PrevOnco has received orphan drug status from the FDA, meaning that if it is approved, the FDA will not approve any competing drugs for seven years.

Orphan drug status is given to treatments for rare diseases. It allows the FDA to promote the development of a drug and optimize its chances for approval. The FDA consults on the design and goals of clinical trials, meaning Apricus can focus trials to provide the specific data the FDA wants to see, making it more likely the agency will approve its application if the trial is successful.

The company said it will conduct a one- to two-year study on around 218 patients with advanced hepatocellular carcinoma, the most common type of liver cancer. Apricus will select patients who have been treated with the drug Nexavar but are no longer responding to it, and for whom surgery is not an option. Patients in the study will receive a combination of PrevOnco, Nexavar, and the chemotherapy drug doxorubicin, or Nexavar, doxorubicin, and a placebo.
If the study is successful, it will be the basis of Apricus' application for marketing approval.

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Today At NATAP

Irreversible inhibition of a protease central to hepatitis C infection; New HCV Protease AVL-192: Study (full text; published pdf attached) -

(11/29/10)

AASLD: New HCV Drugs at AASLD -

(11/29/10)
AASLD: Assessment of Hepatitis C Virus Attitudes Towards Treatment Among Methadone Maintenance Treatment Program Staff -

(11/29/10)
AASLD: 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 -

(11/29/10)

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From Medical News Today

First-Ever Covalent Irreversible Inhibition Of A Protease Central To Hepatitis C Infection
29 November 2010Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, has published research in Nature Chemical Biology demonstrating the first-ever selective irreversible inhibition of a viral...

[read article]

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ScienceDaily

Tiny RNA Shown to Cause Multiple Types of Leukemia
(Nov. 29, 2010) — Whitehead Institute researchers have shown in mouse models that overexpression of the microRNA 125b (miR-125b) can independently cause leukemia and accelerate the disease's progression. Their results are published in this week's online edition of the Proceedings of the National Academy of Sciences (PNAS).

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Beacon NewsFlashes –

November 29, 2010

Gilead Applies For FDA Approval Of New Once-Daily Combination Antiretroviral Pill –

Gilead Sciences announced last week that it has submitted a new drug application to the U.S. Food and Drug Administration (FDA) for a new once-daily combination antiretroviral pill for the treatment of HIV. The pill will contain Truvada (emtricitabine/tenofovir), which is a combination of two antiretrovirals, plus the new antiretroviral rilpivirine (TMC278), which is made by Tibotec Pharmaceuticals. Tibotec applied for FDA approval of rilpivirine in July. Rilpivirine and the once-daily pill have also been submitted for approval in Europe. If approved, the new combination treatment would be the second once-daily combination pill that contains a complete HIV drug regimen; the first is Atripla (efavirenz/emtricitabine/tenofovir), also marketed by Gilead.

For more information, please see the Gilead Sciences press release.

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Vertex Applies For FDA Approval Of New Hepatitis C Drug –

Vertex Pharmaceuticals, a pharmaceutical company based in Cambridge, MA, announced that it has filed a new drug application with the FDA for its investigational hepatitis C antiviral drug telaprevir. Vertex requested a priority review of its application, which shortens the review period from 10 months to 6 months. The application is based on clinical trial data showing that 75 percent of study participants who took telaprevir in combination with Pegasys (pegylated-interferon alfa-2a) and Copegus (ribavirin) were cured of hepatitis C, versus 44 percent who received only Pegasys and Copegus. A majority of study participants were also able to cut their treatment time in half, to 24 weeks. Hepatitis C coinfection is common in people with HIV and is usually more serious than in people who do not have HIV, with disease progression and liver damage occurring more rapidly. For more information, please see the Vertex Pharmaceuticals press release.

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Indian Embassies And Consulates To Drop HIV Test Requirement For Visa Entry –

India’s Ministry for External Affairs has sent a notice to its embassies and consulates worldwide that HIV test requirements should be dropped from visa applications for visiting foreigners. Prior to the announcement, many embassies and consulates required proof of a negative HIV test before granting a visa. The health ministry had recommended the requirement be dropped in 2002, but many embassies and consulates had not enforced the recommendation. The new policy officially states that there are no travel or residency restrictions on people with HIV who wish to travel to India. The move follows similar lifts on travel restrictions for people with HIV in the U.S. and China earlier this year. For more information, please see the article in the Times of India.

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Health News

Being Too Clean Hazardous to Health
1 hour ago Trying to be too clean may backfire for young people's health, according to a study that suggests chemicals from antibacterial soaps and plastics depress the immune system and cause allergies.

Hepatitis C: Interferon-associated retinopathy

Interferon-associated retinopathy:

Interferons are a group of naturally occurring proteins and glycoproteins which have antiviral, antineoplastic, and immune-regulation properties.

They are administered subcutaneously or intramuscularly 1 to 3 times per week. Ribavirin PO is used in conjunction to increase effectiveness. Interferon alpha is used to treat Hepatitis B and C and cancer; interferon beta is used to treat MS. The most common systemic side effects are flu-like symptoms.

Interferon may cause retinal complications as well--and more often than other systemic medication (e.g., hydroxychloroquine or phenothiazines). It may cause vision loss. Some reports state up to 57% of patients taking interferon experience retinopathy (first reported in US in 1993).

The two most common signs with interferon-related retinopathy are cotton wool spots and retinal hemorrhages. They are usually found at the posterior pole around the optic nerve head. Unilateral or bilateral.

They typically occur within 1 to 3 months of treatment which makes it important to see patient for a baseline exam at the beginning of interferon treatment. Cotton wool spots and retinal hemorrhages normally spontaneously resolve during or after treatment. Supposedly there is no difference in incidence with alpha or beta, but there are many more reports with alpha.

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Rarer eye findings

Impaired vision
Retinal artery/vein occlusions
Bilateral oculomotor nerve paralysis
Mydriasis
Anterior ischemic optic neuropathy
Microaneurysms
Subconjunctival hemorrhages
Vascular tortuosity and congestion
Early onset of cataracts
Vitreous hemorrhage
CME
Photophobia

Ocular side effects are more likely if patient . . .
Also has diabetes mellitus, hypertension, or anemia
Is older, female, or has arterial sclerosis
Is on higher dose of interferon
Is also taking antidepressant medication paroxetine (a serotonin-reuptake inhibitor)

Why is this damage occurring?

The exact mechanism is unknown. Possibilities include the occlusion of retinal vessels due to deposition of immune complexes related to activation of complement. Direct damage of the vessel walls may be caused by the medication itself or by Hepatitis C virus. Damage may be due to increased viscosity of the blood.

So, what should be our standard of care?

At baseline, a full fundoscopic exam with photos is helpful to monitor the patient both pre- and post-treatment.

Patient should receive baseline fundus exam before starting interferon treatment.

Inform the MD. Let physicians know that patients need to be monitored closely.
Patient should be followed every 3 months.
Take fundus photos to monitor for progression.
Give patient Amsler grid for home monitoring.
Instruct patient to return ASAP if notes any changes in vision.
If sight is threatened, contact patient's MD to weigh the risks/benefits of discontinuing the medication.

At baseline, a full fundoscopic exam with photos is helpful to monitor the patient both pre- and post-treatment.

Volume 81, Issue 11, Pages 580-586

(November 2010)

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Retinopathy associated with pegylated interferon and ribavirin treatment for chronic hepatitis C

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Shelly Adams, O.D., Mark Ostermeier, O.D.
published online 26 July 2010.

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Abstract
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Background

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Retinopathy is associated with the use of interferon and ribavirin for the treatment of chronic hepatitis C. Common ocular complications include cotton wool spots, retinal hemorrhages, and macular edema.
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Case Report
A 53-year-old black man with a history of drug and alcohol abuse was admitted to the Department of Veterans Affairs clinic for substance abuse treatment. Results of a liver biopsy showed chronic hepatitis C, and treatment with interferon and ribavirin was initiated. A comprehensive eye examination was performed just before the initiation of treatment, and the patient was then periodically monitored for the presence of retinopathy.

No retinopathy was found at the initial visit or at his 1-month or 2-month follow-up examinations. His 4-month retinal evaluation found cotton wool spots in both eyes and retinal hemorrhages in the left eye. The retinopathy persisted for several months but resolved in both eyes before his treatment was discontinued. Throughout his treatment period there were no visual complaints or visual acuity changes.

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Conclusions
Although this patient was visually asymptomatic, and his retinopathy resolved during treatment, we chose to monitor the patient monthly during treatment because of the risk of serious (although rare) ocular complications.

Indian J Ophthalmol.

2010 Mar–Apr;

58(2): 147–148.
doi: 10.4103/0301-4738.60088.
PMCID: PMC2854447
Copyright © Indian Journal of Ophthalmology

Cystoid macular edema and visual loss as sequelae to interferon alpha treatment of systemic hepatitis C

Abstract
Hepatitis C virus infection and interferon treatment may be associated with retinopathy but visual function is generally unaffected. This paper reports the rare occurrence of unilateral macular edema with visual loss. We present an interventional case report with fundus photograph and optical coherence tomography (OCT).

A 48-year-old white male with hepatitis C, treated with a six-month course of pegylated interferon alpha and ribavirin, complained of gradual reduction in the vision of his left eye. Visual acuities were 20/16 right and 20/400 left with clinical examination and OCT confirming cystoid macular edema.

This report shows that cystoid macular edema may rarely occur in association with hepatitis C infection and/or interferon therapy. Physicians and ophthalmologists should be alert to this potential but infrequent association as the resultant visual loss is a significant potential complication that should be discussed when obtaining informed consent for interferon treatment.
Keywords: Hepatitis C, interferon alpha, cystoid macular edema, visual loss

Hepatitis C, virus (HCV) may be associated with an ischemic retinopathy thought to be secondary to HCV-induced vasculitis.[1] Contemporary treatment for chronic systemic HCV infection comprises interferon alpha in combination with ribavirin. The side-effects of interferon include a flu-like illness, fever, fatigue, nausea, hair loss and depression. Interferon treatment has been associated with a retinopathy, characterized by cotton wool spots and retinal hemorrhages, in several prospective case series and has also been reported to cause Vogt-Koyanagi-Harada disease.[2–6] Despite this, patients rarely report subjective visual problems and visual function is generally maintained.

Here we present optical coherence tomography (OCT) evidence of cystoid macular edema (CME) probably due to pegylated interferon alpha treatment for hepatitis C in an otherwise healthy individual with none of the common risk factors for CME. To our knowledge, only two similar cases of this rare and emerging phenomenon have previously been reported worldwide

Case Report
A 48-year-old white male was referred to the ophthalmic accident and emergency by his general practitioner. He gave a six-month history of gradual, painless loss of central vision in his left eye. Visual acuities were 20/16 in the right eye unaided and 20/400 best corrected in the left eye. Both eyes were white with no intraocular inflammation and left eye CME was confirmed on slit-lamp biomicroscopy. Furthermore, OCT showed three symmetric cystic spaces in the external plexiform layer, increased free space between the neurosensory epithelium and retinal pigmented epithelium and disorganization of internal retinal architecture at the macula [Fig. 1]-consistent with the clinical diagnosis of CME.

Figure 1
Fundus photographs and optical coherence tomography scans at first presentation showing cystoid macular edema of the left eye

He was known to be a chronic carrier of HCV (diagnosed in 2004 and attributed to an episode of tattooing) and had undergone a standardized six-month treatment regimen of pegylated interferon-alpha-2a (Pegasys 18 mcg) subcutaneous injections and oral ribavirin 600 mg twice daily under the gastroenterology service of a neighboring hospital. The visual loss had started some weeks into his course, with no subjective improvement on completing the full six-month course, although his viremia was successfully cleared. He had no previous ophthalmic history such as trauma or operations and the left eye was not amblyopic. He was on no other medication and there was no other medical history, including diabetes or hypertension. He was a non-smoker.

Topical treatment was commenced in the form of ketorolac 0.5% eye drops four times daily and dexamethasone 0.1% eye drops four times daily to the left eye. At the three-month follow-up he reported no subjective improvement in vision and acuity remained poor at 20/200 despite a repeat OCT scan showing resolution of edema. Fundus fluorescein angiogram and fundus autofluorescence confirmed macular retinal pigment epithelial atrophy. Active management and further follow-up were declined by the patient.

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Discussion
The incidence of retinopathy associated with interferon treatment varies in literature from 18-86%.[1] The most common lesions seen are cotton wool spots and retinal hemorrhages and actual subjective visual complaints or documented visual loss is infrequent. Our case is highly unusual in both the pathology and also in terms of the level of visual loss. Such ocular side-effects or associations are extremely rare and whilst routine ophthalmic screening at baseline and through the course of peg-IFN-alpha and ribavirin therapy may not be indicated, this case demonstrates that early ophthalmic assessment and treatment in the event of subjective decrease in vision may improve the final visual prognosis.

There are only two similar reports published.[7,8]

The first case was of a 24-year-old male who developed bilateral CME associated with florid retinopathy, the second was a 37-year-old male who developed macular edema with hemorrhages and cotton wool spots. Concurrent hypoalbuminemia and thrombocytopenia was reported in both these patients and cessation of interferon therapy was associated with improvement of vision and normalization of blood parameters. Our patient differs in that the pathology was confined to the peri-foveal area and the visual deterioration was monocular and persistent.

Hypertension and diabetes mellitus have been shown to be risk factors in the development or progression of interferon-associated retinopathy in HCV-infected individuals. However, neither was identified in our patient.

In summary, we present a rare case of CME with attendant visual loss which may be causally related to interferon alpha treatment of hepatitis C. Ophthalmologists and physicians should be aware of the possible ocular side-effects of interferon and whilst treatment of the systemic disease must take priority, we suggest that the potential for transient or longer-term visual loss be discussed when obtaining informed consent for interferon therapy.

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References
1. Zegans ME, Anninger W, Chapman C, Gordon SR. Ocular manifestations of hepatitis C virus infection. Curr Opin Ophthalmol. 2002;13:423–7. [PubMed]
2. McHutchinson JG, Poynard T. Combination therapy with interferon plus ribavirin for the initial treatment of chronic hepatitis C. Semin Liver Dis. 1999;19:57–65. [PubMed]
3. Kawano T, Shigehira, Uto H, Nakama T, Kato J, Hayashi K, et al. Retinal complications during interferon therapy for chronic hepatitis C. Am J Gastroenterol. 1996;91:309–13. [PubMed]
4. Schulman JA, Liang C, Kooragayala LM, King J. Posterior segment complications in patients with hepatitis C treated with interferon and ribavirin. Ophthalmology. 2003;110:437–42. [PubMed]
5. Hayasaka S, Nagasaki Y, Matsumoto M, Sato S. Interferon associated retinopathy. Br J Ophthalmol. 1998;82:323–5. [PMC free article] [PubMed]
6. Kasahara A, Hiraide A, Tomita N, Iwahashi H, Imagawa A, Ohguro N, et al. Vogt-Koyanagi-Harada disease occurring during interferon alpha therapy for chronic hepatitis C. J Gastroenterol. 2004;39:1106–9. [PubMed]
7. Tokai R, Ikeda T, Miyaura T, Sato K. Interferon-associated retinopathy and cystoid macular oedema. Arch Ophthalmol. 2001;119:1077–9. [PubMed]
8. Shimura M, Saito T, Yasuda K, Tamai M. Clinical course of macular oedema in two cases of interferon-associated retinopathy observed by optical coherence tomography. Jpn J Ophthalmol. 2005;49:231–4. [PubMed]


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Journal of Pediatric Gastroenterology & Nutrition:
August 2010 -

Volume 51 - Issue 2 - p 183–186
doi: 10.1097/MPG.0b013e3181b99cf0
Original Articles: Hepatology and Nutrition

Ophthalmologic Complications in Children With Chronic Hepatitis C Treated With Pegylated Interferon
Narkewicz, Michael R

Abstract
Objectives: Interferon treatment for chronic viral hepatitis C (HCV) has been associated with the development of retinopathy in 19% to 29% of adults. Our purpose is to describe the ophthalmologic complications of pegylated interferon-α2a with either placebo or ribavirin in children with chronic HCV (the PEDS-C trial).

Materials and Methods: Prospective, comprehensive ophthalmologic examinations including slit lamp at enrollment and after 24 and 48 weeks of treatment of 114 children participating in a randomized clinical trial.

Results:

One hundred and twenty-eight children were screened for entry, of whom 123 had an eye examination and no child had existing retinal disease. One hundred fourteen children were eligible and were treated. One hundred ten children had an eye examination at 24 weeks and 103 children at 48 weeks. Three of 114 subjects (2.6%) developed documented (n = 2) or possible (1) serious eye complications. One subject developed evidence of ischemic retinopathy (cotton-wool spots) by week 24, 1 developed uveitis by week 48, and 1 reported at week 48 transient (less then 4>

Conclusions: Ophthalmologic complications are infrequent in children who are treated with pegylated interferon-α2a for HCV (2%–3%). Because of the potential severity of ischemic retinopathy and uveitis, prospective ocular assessment should remain part of the monitoring strategy for children who are treated with interferon for HCV

Interferon-Associated Retinopathy: Communicating with Internal Medicine

Ari Wes; Esther S. Hong, MD; and Thomas A. Oetting, MS, MD

July 26, 2010

History of Present Illness:

A 60-year-old gentleman with a history of hepatitis C virus (HCV) infection presents with new floaters in both eyes. He started treatment for HCV with peginterferon and ribavirin 6 weeks prior to this visit.

Four weeks prior to this visit, the patient was seen in our eye clinic at the University of Iowa for a history of floaters and a few episodes of “prisms of light” in both eyes lasting for 5 to 10 seconds. His examination at that time, which included a detailed funduscopic examination, was unremarkable.

The patient was instructed to return to clinic in 2 weeks for a reevaluation, but returned in 4 weeks instead. At this follow up visit he reported that the floaters had resolved.

Past Ocular History:

Presbyopia, no previous ocular surgeries, no trauma
Past Medical History: Hepatitis C virus, tobacco use
Medications: Erythropoetin, peginterferon, ribavirin
Allergies: No known drug allergies
Family and Social History: Non-contributory
Slit Lamp Examination:

Visual acuity, without correction:
OD: 20/20-2
OS: 20/40, with pinhole 20/20
IOP: 12mmHg OD, 11mmHg OS
Pupils: 3 mm -> 2 mm, brisk, equal with no relative afferent pupillary defect
Confrontation visual field: Full OU
Extraocular movements: Full OU
External exam: Normal OU
Slit lamp exam:
Lids/lashes: Normal OU
Conjunctiva: Normal OU
Sclera: Normal OU
Cornea: Clear OU
Anterior chamber (AC): Deep and quiet OU
Iris: Normal OU
Lens: 1+ nuclear sclerosis OU
Vitreous: Clear OU, no Shafer’s sign OU
Dilated Fundus
Disc: pink, sharp borders, multiple cotton wool spots (CWS) surrounding the nerve, small areas of retinal hemorrhages around the nerve OU
Cup to disc ratio: 0.3 OU
Macula: flat OU, few CWS encroaching upon the macula OU
Vessels: normal OU
Periphery: normal OU

Figure 1: Dilated Fundus

Right Eye

Left Eye

Discussion:
The differential diagnosis for diffuse CWS surrounding the optic nerves in both eyes (Figure 1) includes: interferon-associated retinopathy, hypertensive retinopathy, retinopathy associated with leukemia/lymphoma, ocular ischemia, Purtcher's retinopathy (insert link to our Eyerounds case) and HIV retinopathy.

Given that the patient had recently started interferon therapy, was HIV negative, had a normal blood pressure and blood cell count and had no risk factors for ocular ischemia or Purtcher’s retinopathy, the most likely diagnosis was interferon-associated retinopathy.

Many reports have discussed the ocular complications associated with interferon use as an antiviral or antiangiogenic agent. Ikebe first reported this condition in a 39-year-old gentleman who developed retinopathy after administration of intravenous interferon (Ikebe et. al. 1990). Other complications associated with interferon include ischemic optic neuropathy, subconjunctival hemorrhage, retinal hemorrhage, combined choroidal and retinal perfusion deficits and cystoid macular edema (Guyer et. al. 1993, Schulman et. al. 2001, Tokai et. al. 2001). Interferon associated retinopathy occurs in 19% to 69% of adults on interferon therapy (Narkewicz et. al. 2010, Schulman et. al. 2001).

Interferon-associated retinopathy often presents with cotton wool spots, retinal hemorrhages and other retinal microvascular irregularities (Esmaeli et. al. 2001).

These changes occur most notably around the optic nerve head and in the posterior pole (Schulman et. al. 2001). The retinopathy typically presents 3 to 5 months after treatment begins; however, as in our case, it can present as early as 2 to 6 weeks into the treatment (Kadayifcilar et. al. 1999, Okuse et. al. 2006).

Frequent monitoring of patients on interferon is important. Patients with normal exams should be followed every 4 to 6 months while those with retinopathy should be followed more frequently while on treatment.

Fortunately, the ocular findings of interferon-associated retinopathy appear to reverse with cessation of treatment, including CME in one case (Tokai et. al. 2001). When the cotton wool spots encroach upon the macula or when CME is present, it is important for the ophthalmologist to work with the internal medicine team and consider terminating interferon treatment (Meltzer et. al. 2008).

Communicating with Internal Medicine

Our patient’s HCV disease was advanced, and the hepatologist felt that the patient had a guarded prognosis despite interferon treatment. The patient’s initial hepatitis C viral load was very high (>1 million IU/mL).

However, after only 6 weeks of treatment (around the same time that the retinopathy was noted), his viral load became undetectable. We were concerned about visual prognosis as the CWS were close to the macula, but the hepatology service, understandably, had hoped to continue treatment given its success.

Extensive discussions took place between the patient, his family and the hepatology and ophthalmology services. An attempt was made to weigh the potential risk to the eye against the significant benefit of decreased viral load and activity of HCV while on peginterferon. After careful deliberation, the patient decided to continue with the HCV treatment for now, considering his great response thus far and the likelihood that he would not need to be on the treatment for an extended period of time. The ophthalmology service agreed to closely monitor the patient for CME and other signs of worsening interferon-associated retinopathy.

Fortunately on examination 2 weeks later (8 weeks into interferon therapy) the interferon retinopathy was stable if not a bit better (Figure 2).

Figure 2:

Left Eye

Right Eye

Our ophthalmology service will continue to monitor the retinal exam every 4 to 8 weeks and communicate closely with the internal medicine service.
Diagnosis: Interferon-associated Retinopathy

Epidemiology:
No age/gender predilection
Pre-existing arteriosclerosis that affects microcirculation may promote development of retinopathy

Signs:
Cotton wool spots especially around the optic nerve
Retinal hemorrhages
Cystoid macular edema

Symptoms:
Decreased visual acuity
Floaters
Most patients are asymptomatic

Treatment:
Cessation of interferon treatment
May require retinal consultation if complications arise

Differential diagnosis:
Interferon-associated retinopathy
Hypertensive retinopathy
Retinopathy from leukemia/lymphoma
Ocular ischemia

Purtcher’s retinopathy
HIV retinopathy

References
Esmaeli, B., Koller, C., Papadopoulos, N., Romaguera, J. Interferon-induced Retinopathy in Asymptomatic Cancer Patients. Ophthalmology 2001;108:858-860.
Guyer, DR., Tiedeman, J., Yannuzzi, L., Slakter, J., Parke, D., Kelley, J., Tang, R., Marmor, M., Abrams, G., Miller, J., Gragoudas, E. Interferon-Associated Retinopathy. Arch of Ophthalmol 1993;111:350-356.
Ikebe, T., Nakatsuka, K., Goto, M. A Case of Retinopathy Induced by Intravenous Administration of Interferon. Folia Ophthalmol 1990;41:2291-2296.
Kadayifcilar, S., Boyacioglu, S., Kart, H., Gursoy, M., Aydin, P. Ocular Complications with High Dose Interferon-alfa in Chronic Active Hepatitis. Eye 1999;13:241-246.
Meltzer, D. Interferon Retinopathy: A Side Effect from the Treatment of Hepatitis C. Optometry 2008;79 320-321.
Narkewicz, MR., Rosenthal, P., Schwarz, KB., Drack, A., Margolis, T., Repka, MX. Ophthalmologic Complications in Children with Chronic Hepatitis C Treated with Pegylated Interferon. Journal of Pediatric Gastroenterology and Nutrition 2010; Published ahead of print. (PMID: 20512062)
Okuse, C., Yotsuyanagi, H., Nagase, Y., Kobayashi, Y., Yasuda, K., Koike, K., Iino, S., Suzuki, M., Itoh, F. Risk Factors for Retinopathy Associated with Interferon alpha-2b and Ribavirin Combination Therapy in Patients with Chronic Hepatitis C. World J Gastroenterol 2006;12:3756-3759.
Schulman, JA., Liang, C., Kooragayala, LM., King J. Posterior Segment Complications in Patients with Hepatitis C Treated with Interferon and Ribavirin. Ophthalmology 2003;110:437-41.
Tokai, R., Ikeda, T., Miyaura, T., Sato, K. Interferon-Associated Retinopathy and Cystoid Macular Edema. Arch Ophthalmol 2001;119:1077-1079.
suggested citation format:

Wes A, Hong ES, Oetting TA. Interferon-Associated Retinopathy: Communicating with Internal Medicine. EyeRounds.org. July 26, 2010; Available from: http://www.EyeRounds.org/cases/116-Interferon-Retinopathy.htm.
The University of Iowa Department of Ophthalmology & Visual Sciences, 200 Hawkins Dr., Iowa City, IA 52242-1091.

Last updated: 07-26-2010

Merck halts study: HIV integrase inhibitor raltegravir once-daily dosing

Merck halts study of once-daily raltegravir
New and experimental treatments
Keith Alcorn

Published: 29 November 2010

Merck & Co announced today that it has halted a phase III study comparing once-daily dosing of the company’s HIV integrase inhibitor raltegravir to the standard twice daily dose, on the recommendation of the trial's independent Data Safety Monitoring committee.
Although once-daily raltegravir (Isentress) did not prove statistically inferior to twice-daily raltegravir, fewer patients in the once-daily arm had a viral load suppressed below 50 copies/ml after 48 weeks of treatment.


This difference was chiefly driven by poorer viral suppression among people with high baseline viral loads (above 100,000 copies/ml), the company said in a press release.
The study randomised participants new to HIV treatment to receive 800mg of raltegravir once daily or 400mg of raltegravir twice daily, in combination with Truvada (tenofovir/FTC).
Among all participants (n=770), 83.2% of the once-daily group had viral load below 50 copies/ml at week 48, compared to 88.9% of the once-daily group. This difference (-5.7%) was within the pre-defined 95% confidence intervals (-10.7% - -0.83%).
However, among participants with baseline viral load above 100,000 copies/ml (n=304), the difference was greater. While 84.2% of the twice-daily raltegravir group had a viral load below 50 copies/ml within this viral load stratum by week 48, the proportion with fully suppressed viral load in the once-daily group was 74.3%.


Following an initial analysis of the data the trial’s Independent Data Monitoring Committee recommended that all patients in the once-daily arm should be switched to twice-daily raltegravir, and Merck & Co decided to halt the study.


Raltegravir is the first of a new class of antiretroviral drug, called integrase inhibitors, which block the integration of HIV’s genetic material into immune system cells. Raltegravir is currently licensed for twice-daily dosing in the United States and European Union, and is one of the recommended options for first-line antiretroviral therapy in US treatment guidelines.
A number of other companies are developing once-daily integrase inhibitors.
Gilead is currently testing elvitegravir, a once-daily integrase inhibitor that will be boosted with ritonavir or with Gilead’s own proprietary boosting agent, cobicistat.

A phase III clinical trial of a pill combining elvitegravir, cobicistat, tenofovir and FTC is currently underway.
Another once-daily integrase inhibitor is being developed by Viiv Healthcare and Shionogi Pharmaceuticals, and has just entered phase III trials.

Laparascopic finding predicts hepatocellular carcinoma in Hepatitis B virus

Laparascopic finding predicts hepatocellular carcinoma in Hep B virus-related liver disease

Laparoscopic findings of reddish markings predict hepatocellular carcinoma in patients with hepatitis B virus-related liver disease, reports the latest issue of the Journal of Gastroenterology.

For patients with chronic hepatitis due to hepatitis B virus (HBV), factors predicting hepatocellular carcinoma other than high levels of Hepatitis B virus-DNA and alanine aminotransferase (ALT) are needed to prevent hepatocellular development, as many patients with chronic Hepatitis B virus infection fulfill these conditions.
Dr Bon Shoji and colleagues clarified factors predictive of hepatocellular carcinoma development for those patients.

The researchers performed a systematic cohort analysis of 303 consecutive patients with hepatitis B e-antigen, receiving laparoscopic examination for assessment of liver disease.
Laparoscopic, histological, and clinical characteristics were investigated as related to hepatocellular carcinoma development.

Hepatocellular carcinoma occurred in 27 patients during a mean follow-up of 8 years, at the age of 37 years.

Significant associations with hepatocellular carcinoma development were shown for liver cirrhosis, histological activity grade, reddish markings, and older age.
Multivariate analysis revealed that hepatocellular carcinoma development was strongly associated with older age and male gender.

The researchers found that hepatcellular carcinoma occurred more frequently in patients of age 30 years or more even with early stage than in patients of age under 30 years.
Severe reddish markings, a laparoscopic finding of widespread parenchymal destruction, were highly associated with hepatocellular carcinoma development in patients of age 30 years or older at diagnosis, while histological activity grade and ALT level were not. Dr Shoji'a team concludes, "Hepatocellular carcinoma development is associated with older age, male gender, and liver cirrhosis."

"Reddish markings, rather than histological activity or ALT level, can be useful to predict hepatocellular carcinoma for Hepatitis B patients of age 30 years or more."

J Gastroenterol 2010: 45(11): 1172-8229 November 2010

Premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes

In Nature News Today

Dramatic rejuvenation of prematurely aged mice hints at potential therapy.

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Premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes, a study in mice suggests.
Mice engineered to lack the enzyme, called telomerase, become prematurely decrepit. But they bounced back to health when the enzyme was replaced. The finding, published online today in Nature1, hints that some disorders characterized by early ageing could be treated by boosting telomerase activity.

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Continue Reading..........

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Age-Reversing Drugs on the Horizon? Not So Fast

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Researchers have identified targets that could help produce old-age-defying drugs and a fountain of youth for the baby boomer population… but haven’t we heard this all before?
The study, published in Nature this week, used the enzyme telomerase to stop and actually reverse the aging process in prematurely-aged mice.

Telomerase keeps chromosomes structurally sound by beefing up telomeres, the repetitive segments of junk DNA at the ends of chromosomes. Telomeres act as protective buffers for the chromosome’s working genes during cell division, when the chromosome is shortened and genetic material at the tips is lost.

For the new study, researchers created special mice whose telomerase activity could be switched on and off. When telomerase was turned off, the mice aged prematurely.
These animals age much faster than normal mice–they are barely fertile and suffer from age-related conditions such as osteoporosis, diabetes and neurodegeneration. They also die young. “If you look at all those data together, you walk away with the idea that the loss of telomerase could be a very important instigator of the ageing process,” says [lead author Ronald] DePinho.

The mice were grown to adulthood without activating the telomerase gene. Then, the researchers turned telomerase on for a month to see what happened to the mice. By giving the mice back telomerase activity, they were able to not just stop but undo the premature aging.
“What really caught us by surprise was the dramatic reversal of the effects we saw in these animals,” says DePinho. He describes the outcome as “a near ‘Ponce de Leon’ effect” — a reference to the Spanish explorer Juan Ponce de Leon, who went in search of the mythical Fountain of Youth. Shrivelled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver and intestines, recuperated from their degenerated state.

The researchers say drugs that increase telomerase activity could be used to treat premature aging diseases in humans, and could possibly even reverse or delay normal aging. But DePinto and his colleagues stress that the study was just a ”proof-of-concept” experiment to show that changes to telomerase can affect aging.

Before these results can benefit humans who fear the bodily effects of time, many concerns must be answered. Some critics note that the researchers used prematurely-aged mice completely lacking telomerase activity instead of normal mice. Since some normal human cells express telomerase, but not all of them do, there is no telling what the effect of ramping up its activity would be. And even if telomerase-activating drugs do end up working in humans, they could be useful for diseases of premature aging, but wouldn’t necessarily combat normal aging. Says aging researcher David Harrison:
“They are not studying normal ageing, but ageing in mice made grossly abnormal.” [Nature News]

Though mice are often used to develop and test pharmaceuticals, many of those are revealed to be ineffective or unsafe in human trials. This is especially worrisome when mucking with telomerase, whose over-expression has been linked to cancer. The researchers didn’t observe any cancers in these test mice, but telomerase was only activated for one month.
The downside is that telomerase is often mutated in human cancers, and seems to help existing tumours grow faster. But DePinho argues that telomerase should prevent healthy cells from becoming cancerous in the first place by preventing DNA damage.

Researcher Tom Kirkwood told The Guardian that there are a host of other factors involved in aging that have been overlooked in this telomerase-based study.
“The key question is what might this mean for human therapies against age-related diseases? While there is some evidence that telomere erosion contributes to age-associated human pathology, it is surely not the only, or even dominant, cause, as it appears to be in mice engineered to lack telomerase.” [The Guardian]

It looks like anyone hoping for the fountain of youth will have to hang around a little longer while researchers work out the answers to all these questions.