So PDE5 inhibitors, they are phosphodiesterase inhibitors, and they are already used for erectile dysfunction and for pulmonary hypertension. And that’s mainly because it increases cyclic GMP and the downstream mechanisms then work on relaxing vascular smooth muscle, which then allows for more perfusion so that you can get better blood flow. But this class of medications also have what we say polypharmacologic actions, meaning that it works that way, but it also can work by reducing inflammation...
So PDE5 inhibitors, they are phosphodiesterase inhibitors, and they are already used for erectile dysfunction and for pulmonary hypertension. And that’s mainly because it increases cyclic GMP and the downstream mechanisms then work on relaxing vascular smooth muscle, which then allows for more perfusion so that you can get better blood flow. But this class of medications also have what we say polypharmacologic actions, meaning that it works that way, but it also can work by reducing inflammation. And we’ve seen from mouse models and other clinical studies that this class of medication can reduce inflammatory markers such as interleukin-6 and others. In addition, another mechanism is neuroprotection. We can see that it increases things like BDNF, brain-derived neurotrophic factor and other neurotrophins, in addition to reducing phosphorylated tau. So we’ve seen some studies in which some members of this class of medication like sildenafil and mirodenafil that have demonstrated reduction in p-tau levels in mouse models. And we’ve seen improvement in cognition and memory in mouse models using these drugs. So you can imagine that this class of medication may be appropriate for looking into Alzheimer’s disease. In addition, we’ve seen retrospective studies where we look at, say, database of different people who have used PDE5 inhibitors for new onset erectile dysfunction and found a reduced incidence of developing Alzheimer’s disease for those who have taken it. So certain ones are more likely to cross the blood-brain barrier, meaning that they get access to the central nervous system, which may be a better type of medication to use for Alzheimer’s disease.
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