THE PLACEBO EFFECT – The Specter Still Haunting?
Was it just the simple “Placebo Effect” that scared them from taking the risk of moving forward? Or was it something more complex that we missed? We settle the question once for all in the discussion that follows.
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V.A. Is Angiogenesis Therapy Dead?
We did not ask that question. “Is Angiogenesis Therapy Dead?” was the title of a scientific session at last years’ annual American College of Cardiology meeting in New Orleans. The answer, at least from the major players, who are still well into the Phase II-III clinical trials is a resounding “NO”. And all the evidence so far compels us to side with the proponents of “NO”. - - - - - - - - But the major culprit that has been accused of really bogging down the progress of angiogenesis therapeutics is the notorious “Placebo Effect”.
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TRANSLATIONAL PARADOX – Neocardiogenesis: A Whole Different Ballgame
Is Mother Nature really keeping the secrets or did we lose something in translation? Secrets are always camouflaged in the visuals of what is obvious. Let us closely look at the obvious and see if we can unmask the secret if at all there is one.
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For all the aforementioned reasons the approaches for treating CAD is neither like any other gene therapy approach, nor it is like any other protein or cell therapy approach that biopharmaceutical industry knows of. Therefore applying those conventional treatment design approaches ditto to regenerative cardiology will not produce the best results. But the best part of this analysis is that none of these perceived problems are insurmountable. In the Chapters that follow we will try to formulate a strategy to address these problems.
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CATCH 22- Obsolescence Of Convention
In a recent review of the role of cardiovascular co-morbidities (such as those discussed above) in inhibiting the effectiveness of angiogenic therapies, Kinnaird et al emphasized on the urgent need of developing strategies to overcome this formidable problem. However the future directions suggested by them include further gene manipulation and search for new therapeutic targets, which are quite research intensive, and do not offer much to rescue the currently active coronary angiogenesis clinical trial programs. Not undermining the importance of continued research into new areas, we are reluctant to completely write off the existing neocardiogenesis approaches, as our investigations indicate that the problems with the deployment of the current therapeutic agents aren’t undefeatable.
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However, we have a different take on the failed clinical trial problem, whether protein or gene based or stem cell based. Our research, in general, places the initial onus of inefficacy not on the inadequacy of the neocardiogenic agents, but on the inadequacy of the host response. If that is indeed the case the problem can be fixed with relative ease as we see in the next Chapter.
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WAY OUT- Ridding The Triple Cripple
Until recently no non-invasive diagnostic procedure could diagnose ED. However, a few companies that are discussed here, are pioneering the diagnosis of endothelial dysfunction in an everyday clinical setting by measuring, either peripheral vascular reactivity, or noninvasive plethysmography, or arterial stiffness or changes in elasticity of arteries. Using one of these commercially available tests to monitor endothelial dysfunction in regenerative cardiology clinical trials will give a fairly good control over an otherwise uncontrollable intrinsic study confounder.
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We now know just enough of regenerative pathophysiology of human heart to be able to diagnose and possibly cure the problems. The successful approach to regenerative cardiology perhaps will come from integration of diverse expertise from different collaborating companies. Based on what we have unearthed in our research project, we believe at least three different types of technological expertise need to partner to produce a successful regenerative cardiology product.
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