Interferon Beta DNA treatment

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Interferon Beta DNA treatment

Postby scoobyjude » Mon Mar 26, 2007 4:46 pm

If I understand this correctly, you would only need one administration of Interferon Beta intramuscularly and then your body would produce it's own. Did I read this right?

Interferon Beta DNA Treatment Delivered with Ichor Technology Reduces Atherosclerosis Progression in Mice
26 March 2007, 4:39pm ET

NEW ORLEANS, Mar 26, 2007 (BUSINESS WIRE) --

Summary: Proprietary DNA delivery technology enables sustained Interferon-beta production from muscle cells - reduces atherosclerosis progression in mouse model of heart disease

Research conducted at Cleveland Clinic and presented today at the American College of Cardiology's 58th Annual Scientific Session showed that a single administration of DNA encoding the anti-inflammatory protein interferon-beta (IFN-beta) using Ichor Medical System's TriGrid Delivery System (TriGrid) reduced the development of plaque formation in a mouse model of atherosclerosis.

"The sustained production of this protein reduced the atherosclerotic lesion size and tissue-damaging inflammation that characterize the blood vessels of these mice with atherosclerosis," said Marc S. Penn, M.D., Ph.D., principal investigator from Cleveland Clinic.

While preliminary, these results broaden the support for the use of the electroporation-based TriGrid as an enabling platform technology to provide continuous endogenous production of therapeutic proteins from a patient's own muscle. Previous studies done in collaboration with Dr. Vince Tuohy's lab at Cleveland Clinic demonstrated that one-time delivery of the IFN-beta gene intramuscularly with the TriGrid in a mouse model of multiple sclerosis (MS), resulted in sustained production of IFN-beta and a similar reduction in the severity of clinical disease as compared to a separate group of mice dosed every other day with recombinant IFN-beta (Molecular Therapy 14(3): 416-422 (2006)). This study suggests that in vivo gene transfer of the IFN-beta gene may provide a convenient and viable alternative to constant life-long dosing of the recombinant form of IFN-beta for patients with MS.

Together, these data demonstrate both the potential therapeutic and economic value of Ichor's technology.

"The TriGrid platform makes treatments like interferon-beta more reasonable because a single administration of the gene using the TriGrid results in consistent production of the therapeutic protein in muscle for extended periods of time resulting in a vastly reduced cost," said Ichor CEO Bob Bernard.

The TriGrid is also being used to enable endogenous protein production for DNA-based treatments of HIV, Hepatitis B and C, malaria, avian flu and various forms of cancer in pre-clinical and clinical trials worldwide.

About Cleveland Clinic

Cleveland Clinic, located in Cleveland, Ohio, is a not-for-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Cleveland Clinic was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. U.S. News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual "America's Best Hospitals" survey. Approximately 1,800 full-time salaried physicians and researchers at Cleveland Clinic and Cleveland Clinic Florida represent more than 100 medical specialties and subspecialties. In 2005, there were 2.9 million outpatient visits to Cleveland Clinic. Patients came for treatment from every state and from more than 80 countries. There were nearly 54,000 hospital admissions to Cleveland Clinic in 2005. Cleveland Clinic's Web site address is www.clevelandclinic.org.

About Ichor Medical Systems

Ichor Medical Systems, a privately-held biotech company, is developing products based on the in vivo application of electroporation to enhance intracellular delivery of DNA drugs encoding therapeutic proteins or antigens for vaccines. Ichor's proprietary TriGrid(TM) Delivery System (TriGrid) is the first and only integrated and fully automated system for electroporation-mediated DNA administration. This system allows the site of DNA injection, placement of electrodes, rate of DNA administration and timing of electrical pulse application to be consistent among different operators and patients. As a result, Ichor's TriGrid enables safe, effective and reproducible clinical application of electroporation in a manner capable of supporting development and commercialization of DNA-based products. The Ichor system is currently being used on three continents in a wide range of pre-clinical and clinical studies for potential treatments of melanoma, HIV, Hepatitis B, Avian Flu and Multiple Sclerosis.

SOURCE: Ichor Medical Systems
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Postby dignan » Mon Mar 26, 2007 7:11 pm

I read it same way you did, right or wrong. On the one hand this sounds great, on the other hand, it's still pre-clinical for MS, so that means maybe 8 years from being approved, if ever. I really hope by 2015 we have far more effective treatments than good old interferon beta, even if this trigrid system works better than injecting it.
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Postby scoobyjude » Mon Mar 26, 2007 9:09 pm

Me too Dignan. By 2015 I don't even intend to be worrying about MS. At least not in the way we are now. And I definitely don't intend to be injecting anything!!
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Re: Interferon Beta DNA treatment

Postby NHE » Sun Apr 01, 2007 8:26 pm

scoobyjude wrote:If I understand this correctly, you would only need one administration of Interferon Beta intramuscularly and then your body would produce it's own. Did I read this right?

Actually, it's not treatment with interferon-beta, it's treatment with interferon-beta DNA. Thus, this puts the treatment in the same category as gene therapy. From the article, it describes the TriGrid system as a method of electroporation. This uses a short duration, high voltage electrical shock to blast small holes into the cell membranes. Scanning electron micrographs of cells subjected to electroporation literally look like the cells have been hit by a microscopic shotgun. Once there are holes in the cell's membranes, the DNA with the gene encoding interferon-beta can be taken up by the cells. Some of this DNA will get incorporated into the target cells genome in the nucleus and then muscle cells which normally don't produce interferon-beta will start producing it.

One technical problem with an approach such as this will likely be with dosage control. Even with a set number of copies of the interferon-beta gene, it will be difficult to control how many cells the DNA gets into. Additionally, not every cell which takes up the DNA will produce the interferon-beta protein. Thus, if this procedure goes forward, I suspect that people will need to have their circulating levels of interferon-beta checked and the amount of DNA injected may need to be adjusted. It would also be interesting to know what the long term effects, if any, there might be on the muscle tissue producing interferon-beta. For example, I use Avonex and alternate the injection from one leg to the other every week. However, if I happen to forget which leg I used the week before and inject into the same leg two weeks in a row, I find that the injection is more painful than if the muscle had been given an extra week to recover from the prior injection. Of course, this symptom could be due to the IM injection itself and have nothing to do with interferon-beta's affects on muscle tissue.

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Postby scoobyjude » Mon Apr 02, 2007 4:37 pm

high voltage electrical shock to blast small holes into the cell membranes


Yikes!! It sounds very complicated and a little scary. Hopefully they can find better treatments that will be easier and more effective to administer.
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