Alnylam, Medtronic RNAi drug-device combo wows with preclinical data

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For years now, scientists have touted the enormous promise of using RNAi treatments to turn off bad genes that cause disease, but delivering the drugs effectively to their target cells, particularly in the brain, remains a challenge.

Alnylam Pharmaceuticals ($ALNY), Medtronic ($MDT) and the nonprofit CHDI Foundation say they've found a way in preclinical trials to effectively deliver their RNAi drug-device combination to treat Huntington's disease to its target in the brain. They point to results suggesting that their test led to "significant silencing" of the huntingtin gene in the striatum and surrounding brain tissue. Details are published in the journal Experimental Neurology.

RNAi research has been a struggle, in part because of drug delivery challenges, with Big Pharma rivals including Novartis ($NVS), Merck ($MRK) and Roche ($RHHBY) cutting back their RNAi research in recent years. Those companies won't rethink their decisions just yet, because the Alnylam/Medtronic finding is very early, and further testing in animals and people will be crucial to see if it can be replicated successfully. But promising early results point to a possible way to make an approvable product that delivers an RNAi Huntington's treatment directly to where it is supposed to go, the collaborators say.

"The preclinical results suggest scalability of RNAi therapeutic delivery to the striatum of Huntington's patients," Gregory Stewart, a scientist focused on central nervous system drug therapy research at Medtronic, said in a statement.

The scientists, working with the laboratory of Don Gash at the University of Kentucky College of Medicine, tested the delivery of a small interfering RNA (siRNA) drug that targets the huntingtin gene, using an implantable infusion system and convection-enhanced delivery. They found that the drug distributed broadly to its targeted areas while using intrastriatal convection-enhanced delivery for seven days. Also, the level of drug distribution silenced the huntingtin gene through the putamen 45% on average, and helped reduce levels of the huntingtin protein.

Alnylam and Medtronic and their collaborators see the data as pointing toward using continuous convection-enhanced delivery of an RNAi drug to treat Huntington's disease, because it could achieve "psychologically significant coverage" of the targeted areas with "therapeutically relevant" levels of the drug.

- here's the release

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