Pulmonary Arterial Hypertension treatment – clinical case by top expert (11)

Pulmonary Arterial Hypertension treatment – clinical case by top expert (11)


– Is there a clinical case you could discuss
that could illustrate some of the lung disease topics that we discussed?
Dr. Anton Titov MD – There are a whole host of clinical cases. I think some of the the things that come to
mind: we have obviously a whole degree of patients who present [with symptoms of lung
disease]. And when I think of some of our patients who
have presented with very advanced lung disease, there we’re using multi-modality treatments. So these are patients who generally have idiopathic
pulmonary arterial hypertension, who present in right heart failure, who we start on aggressive
therapy with intravenous prostacyclins as well as combination therapy with endothelin
antagonists and PDE5 inhibitors. But that’s the limits of our ability there. We’ve worked with companies to develop novel
treatment approaches, including fully implantable drug delivery systems that we’re waiting for
FDA approval on at this time. But we’ve been able to get rid of Hickman
catheters that way, and put everything inside the body, so that we limit the infection risk
and a complication risk with the drug delivery systems. We’ve also been able in those patients to
think outside the box and use targeted therapy, like anti-inflammatory immunosuppressive therapies
in low doses that might actually help reverse some of the abnormal pathway functions that
are driving [lung blood vessel] remodeling. An example is using a drug like tacrolimus,
which is normally used for transplantation and immunosuppression, whereas in low doses
we have evidence, in working with collaborators at Stanford, that tacrolimus may actually
reverse some of the genetic abnormality that is acquired in PAH lung disease. So we’ve been treating some of our more advanced
patients with tacrolimus. There’s also targeted therapy that we’ve been
able to use in these patients that targets mitochondrial function. Because we’ve learned in all of these patients
that there is dysfunction and really an inefficient approach to metabolism whereas they tend to
shift to glycolysis rather than oxidative phosphorylation. So using different medications that we know
might do the reversal of that, we have started treating some of these patients. And a nice thing is that patients have responded
well to these interventions. It’s very interesting because you showed that
there is a mitochondrial dysfunction [in lung diseases]. The mitochondria are the sort of energy-generating
power stations of the cell. It could explain some of the shortness of
breath that the patients with lung disease are experiencing. Yes, mitochondria. When I think about medicine, and as an intensivist,
when I think about critical care, and patients who come in with severe disease like septic
shock or whatever kind of shock you want to address, it’s probably ultimately the mitochondria
that are getting damaged or become dysfunctional or become hibernating. And if we have targeted therapies that can
get into the cell, get into that mitochondria and regenerate it, then we will probably change
how we care for patients. One of the goals when we started our stem
stem cell studies is that when we see patients in heart failure, there’s a clear shift in
metabolism to glycolysis from oxidative phosphorylation in the myocardium. And we thought that because of data from in
vitro studies, where if you take stem cells and you mix them with diseased cells, stem
cells and diseased cells can fuse and transfer mitochondria and restore normal bioenergetics. We thought, why can’t we do that in the living
heart? And that’s why we did our initial stem cell
studies to infuse stem cells, and we looking at mesenchymal stem cells infused directly
into the right coronary artery in these models. And we were able to see that these cells go
in, they proliferate, and they actually were surviving much longer than any other prior
stem cell studies had shown. So I think things like that are novel approaches
that could change the way we treat these [lung disease and heart failure] patients in the
long run. Well, mitochondria – and the statins also
work on the mitochondria. Yes, a number of drugs [work on mitochondria]
and that gets to repurposing: a lot of what we use for one treatment indication, we’re
learning that it may be useful in other disease indications. I think not only could that save money but
it could save time as far as getting drugs approved for treating these lung diseases. So we’re open to any novel idea. If someone comes up with an idea and it makes
physiologic, metabolic, biochemical sense – it’s worth investigating!