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bit of a long shot but Dirk mentioned ddRNAi could be particularly useful for brain diseases:

 

First Gene Therapy Trial In Parkinson's Shows Promising Results

Posted on October 2, 2010 by dertli Parkinson's Disease Drug

 

Researchers have identified a potential new drug target for the treatment of Parkinson's disease and possibly for other degenerative neurological disorders.

 

In an upcoming issue of the journal Science, the investigators describe finding, in cellular and animal models, that blocking the action of an enzyme called SIRT2 can protect the neurons damaged in Parkinson's disease from the toxic effects of alpha-synuclein, a protein that accumulates in the brains of Parkinson's patients. The study, which also suggests that inhibiting this pathway could help in the treatment of other conditions in which abnormal proteins accumulate in the brain, is receiving early online release on the Science Express website.

 

"We have discovered a compelling new therapeutic approach for Parkinson's disease, which we expect will allow our scientists ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ as well as those at pharmaceutical and biotech companies ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ to pursue innovative new drugs that will treat and perhaps even cure this disorder," says Aleksey Kazantsev, PhD, director of MGH-MIND Drug Discovery Laboratory, who led the Science study. "Since the same sort of aggregation of misfolded proteins has been reported in Huntington's and Alzheimer's diseases ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ as well as Lewy body dementia, which also involves alpha-synuclein deposits ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ we plan to test this approach in those conditions as well."

 

Parkinson's disease ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ characterized by tremors, rigidity, difficulty walking and other symptoms ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ is caused by the destruction of brain cells that produce the neurotransmitter dopamine. In recent years researchers at several centers have been studying the role of alpha-synuclein accumulations in dopamine-producing neurons, observed in patients with both inherited and sporadic Parkinson's disease. MGH-MIND investigators have discovered that, in Parkinson's, the alpha-synuclein molecule folds abnormally and form aggregates called inclusion bodies. Such inclusions of other abnormal proteins are seen in several disorders, but whether inclusions are toxic or protective to neurons has been controversial.

 

In a paper published last year in the Proceedings of the National Academy of Sciences, a research team led by Kazantsev analyzed ways to reduce the size of inclusions containing misfolded versions of alpha-synuclein or of the Huntington's disease-associated protein huntingtin. They found that a compound called B2, which promotes the formation of larger inclusions, paradoxically appeared to reduce toxicity in cellular disease models, possibly by reducing the overall number of inclusions.

 

In the current study, the investigators began by seeking the mechanism underlying the observed effects of B2. Assays of the compound's activity against a panel of key enzymes identified only one significant association ÃÆâ€â„¢ÃƒÆ’ƒâہ¡ÃƒÆ’‚¢ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â€š¬Ã…¡Ãƒâ€šÃ‚¬ÃƒÆ’…¡Ãƒâہ¡ÃƒÆ’‚¬ÃƒÆ’¢Ã¢Ã¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã‚¡ÃƒÆ’‚¬Ãƒâ€Â¦ÃƒÆ’¢Ã¢Ã¢â‚¬Å¡Ã‚¬Ãƒâ€¦Ã¢â‚¬Å“ a weak but selective inhibition of SIRT2, which is known to regulate the cell cycle and may have a role in aging. An experiment using RNA interference to suppress SIRT2 and a related enzyme in human cell lines expressing alpha-synuclein confirmed that only the inhibition of SIRT2 reduced alpha-synuclein toxicity.

 

Kazantsev's team then developed and identified more powerful inhibitors of SIRT2, based on the structure of B2. One of these novel inhibitors called AGK2 had 10 times the potency of B2 and was shown to protect dopamine-producing neurons from alpha-synuclein toxicity in cultured rat neurons and in an insect model of PD. Several additional compounds that act on the SIRT2 pathway have been identified, some which may be even better than AGK2 as candidates for drug development.

 

SIRT2 is known to act on a major protein component of microtubules, cellular structures that help move objects within cells, among other functions. The researchers theorize that inhibiting SIRT2 might promote microtubule-dependent transportation of alpha-synuclein into large aggregates; or it could strengthen microtubules that have been destabilized by misfolded alpha-synuclein.

 

Kazantsev explains, "For Parkinson's disease, we can now pursue a straightforward drug development process by identifying potent and selective candidates from this class of compounds that can be tested in animal studies and eventual human trials. One of the most satisfying aspects is how this discovery validates our approach to drug discovery, which incorporates both the most advanced tools for screening candidate compounds and outstanding collaboration with our clinical and scientific experts in human disease." Kazantsev is an assistant professor of Neurology at Harvard Medical School.

source:www.emaxhealthyok

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Dirk Haussecker said... In addition to a few IP issues I guess, that's of course the big question for mdRNA and their shareholders. I would only say as much that the needs for RNAi expertise and IP vary in Big Pharma and there should be strategic fits. It all comes down to how much in return for what. You also have to remember that there is not only competition between Big Pharma but also competition between some of the smaller RNAi Therapeutics players. To get the big upfront/takeover offer, however, you have to be able to show the ability to knock down genes following systemic administration in primates at acceptable tox and have the clinical scale-up to go with it.

I think this goes back to may ...No more IP issues, sounds like Benitec to me

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Marina Biotech Announces Patent Allowance Covering a "Tumor Homing" Peptide

 

Announces Additional Early Research Effort in siRNA Delivery to the Lung

http://i.marketwatch.com/MW5/content/story/images/PR-Logo-Marketwire.gif

 

 

 

BOTHELL, WA, Oct 06, 2010 (MARKETWIRE via COMTEX) -- Marina Biotech, Inc. /quotes/comstock/15*!mrna/quotes/nls/mrna (MRNA 2.28, -0.01, -0.44%) , a leading RNAi-based drug discovery and development company, today announced that the Intellectual Property Office of New Zealand (IPONZ) has issued a Notice of Acceptance for patent application 566281. Allowed claims cover one of the company's key delivery peptides that contains a "tumor homing" motif. This patent application adds to the Company's broad existing peptide based delivery technology which includes nanoparticle forming peptides and a Trp-cage peptide phage display library for selection of targeting ligands. Marina Biotech also announced the establishment of another early research effort with a major pharmaceutical company focused on the evaluation of its proprietary amphoteric liposomal formulations for pulmonary delivery. Additional details of the relationship were not disclosed. This adds to the Company's existing ongoing research and collaboration efforts and represents the sixth such effort announced in the last 12 months.

 

"In the past year, we have strengthened our intellectual property position by adding over 55 issued patents to our global patent portfolio with additions that significantly protect our nucleic acid delivery technology," stated J. Michael French, President & CEO of Marina Biotech. "Including this recent patent allowance, we now have over 50 patents worldwide protecting a broad array of nucleic acid delivery platforms including our peptide nanoparticle delivery technology, which includes this 'tumor homing' peptide; our tkRNAi platform for bacterial delivery of expressed short hairpin RNA;

i say let the licensing fees start about time we are going to see some $$$$$$$$
and our amphoteric liposomal delivery platform. Furthermore, Marina Biotech has over 200 pending patent applications worldwide, which include patent applications for our novel and proprietary DiLA2 delivery platform and we have one of the youngest patent estates in the RNAi sector providing patent protection well into the late 2020s."

 

Effective delivery is a well-recognized hurdle in the development of RNAi-based therapeutics and Marina Biotech has taken a multifaceted approach to solving the challenges in the development of siRNAs as drugs. The addition of this patent further strengthens the Company's leadership in the field of RNAi delivery and complements the existing DiLA2 liposome, amphoteric liposome and tkRNAi technologies.

 

About Marina Biotech, Inc. Marina Biotech (formerly known as MDRNA, Inc.) is a biotechnology company, focused on the development and commercialization of therapeutic products based on RNA interference (RNAi). Marina's pipeline currently includes a clinical program in Familial Adenomatous Polyposis (a precancerous syndrome) and two preclinical programs -- in hepatocellular carcinoma and bladder cancer. Marina Biotech's goal is to improve human health through the development of RNAi-based compounds and drug delivery technologies that together provide superior therapeutic options for patients. Marina Biotech's global portfolio includes 63 issued or allowed patents; 56 U.S. patent applications; 145 foreign patent applications; and 8 PCT applications providing broad coverage for siRNAs, chemistry, delivery and gene targets. Additional information about Marina Biotech is available at http://www.marinabio.com.

 

 

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latest from The Hausse:

 

QUOTE For example, like myself and I believe an increasing number of other people in the sector, mdRNA agrees that DNA-directed RNAi could be very powerful for neurological applications and therefore be of interest.

I think you posted this back in may , this mdrna is poping up every where...
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