Can MicroRNA Reverse Heart Disease?

Regulus Therapeutics, a joint venture between Alnylam (ALNY) and Isis (ISIS) formed to discover, develop, and commercialize microRNA-based therapeutics, announced the publication of new research in the journal Nature on the role of a microRNA, known as miR-21, in heart failure.

Apparently, this is the first time a microRNA drug has reversed or halted a disease (not biomarkers for the disease, but the disease itself) in an animal model. Interesting science no doubt, but before we anoint microRNA therapy as the hottest area in drug development we should keep in mind a few things:

1.) A rodent heart, while a decent quick and dirty model, is vastly less complicated than even a dog or pig heart. Proof in these models would be much more convincing. Of course, you do the rodent model first… I’m just saying we shouldn’t put too much stock in curing a disease in an inferior animal model.

2.) Dosing by injection to the chest 3x a day is rather inconvenient. I would think patient compliance might be an issue (tongue in cheek). Of course, the formulation will be improved but the main issue with all of these oligo / RNAi type drugs is the delivery. Great research tools… terrible drugs and until I’m proven wrong, I invest based on a search for drugs (reward), not fancy lab techniques (risk).

I’m not trying to be a hater here, but when a company puts out a press release saying they have positive animal data, I’m always skeptical of the motives. The study is published in Nature… that should be all the publicity you need.

Comments

[jcder:]

1) the mouse model is just as complex as a pig or dog model, and just as applicable as an indicator of potential human results (where did you get your PhD, anyway?) 2) the current delivery method is the only one that currently works, but that will change sooner or later, i.e. by transfection via an otherwise inert virus. To say that it is a "terrible" drug when it shows such promise is to miss the point. Of course it will be years, even decades, before drugs of this type hit the market. Their potential, though, is astonishing.

2008 Dec 01 12:20 PM

[Jeff P:]

There is one other glaring downfall of RNAi therapy that make your objections seem trivial - specificity. RNAi has been documented to not only silence its intended target, but multiple unintended targets as well. Sure, it may cure your heart disease, but how many other sequences of DNA is it silencing in the ~1 trillion cells of the human body.

2008 Dec 02 01:03 AM

[jcder:]

It is true the RNAi therapeutics will impact targets other than their intended targets. Isn't that also true for any prospective drug? The key is to balance therapeutic benefits with their side effects. Don't forget that RNAi compounds of this type are frequently identical to endogenous molecules used for the similar purposes. In this sense, they are potentially safe to use therapeutically as they are ALREADY used for "natural" purposes.




On Dec 02 01:03 AM Jeff P wrote:

> There is one other glaring downfall of RNAi therapy that make your
> objections seem trivial - specificity. RNAi has been documented to
> not only silence its intended target, but multiple unintended targets
> as well. Sure, it may cure your heart disease, but how many other
> sequences of DNA is it silencing in the ~1 trillion cells of the
> human body.

2008 Dec 03 03:09 PM