SPC3649 HCV Drug reset the immune system in non-responders

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SPC3649 HCV Drug reset the immune system in non-responders

From : hepc.bull -January 2010

DANES SWING A MIGHTY SWORD AGAINST HCVby Laird

A recent article published in Science Expressadded another drug as a candidate fortreatment against hepatitis C Virus (HCV)that has shown very exciting possibilities.

Clinical trials demonstrate that it is indeedwell tolerated, which may slightly differentiateit from protease and polymerase inhibitorscurrently in the pipeline as the next additionto the success of treatment.

Telaprevir and Boceprevir, when combined with standardtherapy, increase the SVR rates in formernon-responders with genotype 1 currentlyare producing increased rates of sustainedviral response (SVR) in former nonresponderswith genotype 1, raising SVR(and chances of a cure) from 15% to around70%.

There are some issues of drug resistancethat develop when some of these proteaseand polymerase inhibitors are used..

Some side effects presently end the treatmentfor about 14% of participants. Early reportingsuggests that this may not be so with thisrecently announced drug.

The compound in question is calledSPC3649.

The only side effect noted so far isa cholesterol lowering effect. It has produceda 350-fold reduction in HCV levels lastingfor two months following 12 weeks of treatment.

There was an additional advantagediscovered, as the drug appears to reset theimmune system in non-responders. Sincethere is a genetic disposition involved, somepeople have their immune system shut downrather than fight off the virus when they startinterferon. It appears that this new drug“actually reset a number of interferon respondinggenes… that were deregulated atthe onset of treatment,†according to SantarisPharma scientist Henrik Orum. “These genesare normalized… suggesting that the gene innon responders could be reset… [to responderlevels].â€

These studies show no evidence of viralescape, indicating that there will be fewercases of relapse and non-responders. Viral“escape†or rebound refers to HCV geneticmutation, since the virus has a knack oftransforming itself to escape treatment.

Incidentally, this response could be followedby a jump of ALT during treatment,which might indicate viral breakthrough.This happens with interferon treatment andstill happens with the use of the new complementarydrugs nearing development in10 to 15% of cases. This is a good reason tocheck your ALT regularly during treatment.They may be able to alter approaches atthis point or consider treatment termination.The target of the SPC3649, microRNA122,that is required for HCV replication.

All of the six genotypes and over fiftysubtypes of HCV are ‘addicted’ to microRNA122.The compound likely binds to itmaking it unavailable to HCV. Since microRNA122is universal in many livingorganisms it is possible that the drug willwork for everyone. “This paper adds to thegrowing body of evidence,†says Orum,“that the inhibitor platform has the potentialto transform the field of RNA targetedtherapeutics making specific silencing ofRNA targets involved in disease a reality inhuman medicine in the longer run.â€

Other recent developments with this technologymay have significant impacts on treatmentsfor HIV, inflammatory disease and even cancer.

It demonstrates a real potential forHCV treatment in a cocktail with the otherinhibitors without the need for interferon.In the writer’s view announcements likethis are likely to be counterproductive in BC.It is the practice for the current governmentto limit access to interferon treatment forarbitrary and contrived reasons.

Present standards for qualifying for treatment requireabnormally high ALT for three months whenwe all know that it is possible to die of cirrhosiswithout any real change to ALT levels.

A study by Dr Rob Myers in Calgary demonstratedthat forecasts by epidemiologists forhepatitis mortalities were too low, with fourtime increases in hospital related liver visits;75% of cases are under reported.

Dr Myer's paper came with the potentmetaphor likening the disease to a sleepinggiant awaking. Still it is likely that groggypolicies will continue with the distortedthinking of BC governance rationalizing thatthere are more effective treatments on theway.

People will continue to fall into theabyss of brain fog and other costly symptomsas long as treatment is denied.

Also, the people who suffer increased side effects frominterferon such as anaemia will continue tobe denied erythropoietin and subsequentlyhave their hopes dashed as they are deniedcomplementary medicine.

After all, if the white blood cell count goes down we knowthe treatment is working, right?Dr Myer’s sleeping giant still lies in afitful sleep.

http://www.hepcbc.ca/bulletin/2010/2010-01.pdf

Sources:www.latimes.com/news/nationworld/nation/la-scihepatitis-c4-2009dec04,0,1848983.story (Myers, RP, Can J Gastroenterology Vol 22 No 4April 2008 www.pulsus.com/journals/abstract.jsp?jnlKy=2 & atlKy=7977 & isuKy=779 & isArt=t & HCtype=Consumer www.hivandhepatitis.com/hep_c/news/2008/061308_c.htmlwww.hivandhepatitis.com/2007icr/aasld/docs/110607_a.html

http://Hepatitis Cnewdrugs.blogspot.com/2010/01/spc3649-hcv-drug-reset-immune-system-in.html