PnPP-19: Promising ED Medication Derived from Spider Venom
Over the past few centuries there have been numerous attempts to find an all-natural means of treating erectile dysfunction but the effectiveness of herbal ED remedies and dietary supplements has always been mediocre at best. However, recent studies by a group of scientists based in Brazil show that an effective ED medication derived from a naturally occurring substance does exist after all.
What makes this new potential treatment, currently codenamed PnPP-19, very unusual is that it is not of herbal origin. It is derived from PnTx2-6 – a protein from Phoneutria nigriventer spider toxin. The interest towards the characteristics of this spider’s venom was sparkled by the fact that a Phoneutria nigriventer bite can cause priapism in humans. The spontaneous erections triggered by the venom are very hard and last for many hours. Unfortunately, they may also result in permanent loss of potency due to structural damage to the penis. Although only 2.3% of the cases of Phoneutria nigriventer bites are serious enough to require antivenom, this species of spiders are still considered to be a threat to humans.
Observing the effects of PnTx2-6, the scientists attempted to create a non-toxic derivative of it that would retain the capability to induce erections in humans without causing any adverse reactions. The research led to the synthesis of PnPP-19, a peptide that supposedly is the active core of PnTx2-6. It consists of only 19 amino acid monomers and is simple to synthesize but, at the same time, it shows high specificity and low toxicity and immunogenicity.
The results of the study by Yonamine et al strongly suggest that the PnTx2-6 toxin affects erectile function via NO/Cyclic Guanosine Monophosphate (cGMP) pathway, which makes it somewhat similar to PDE5-inhibitors. However, it doesn’t mean that the new toxin-derived medication will not work in PDE5i non-responders. Its effect does not depend on phosphodiesterase 5 (PDE5) inhibition and it was shown to restore erectile function in diabetic, hypertensive and elderly animals in rat model studies, so similar results are expected in humans as well.
Another advantage of PnPP-19 is that it is able to permeate human skin, and, therefore, can be used as a topical formulation. According to the 2019 study by Silva et al, the peptide shows a rather low permeability of 10% but that can be enhanced by means of more advanced transdermal delivery systems such as DermaSys or similar.
PnPP-19 was shown to enhance the effect of sildenafil when the medications are taken together. Besides, there’s a 2018 study by Freitas et al analyzing the pain-relieving effects of PnPP-19. It turns out that this peptide also activates opioid receptors, so there’s a potential for using it as a harmless alternative to narcotic pain relievers.
Overall, the development of a PnPP-19-based ED medication gives hope to patients who don’t respond to PDE-5 inhibitors or can’t use them due to cardiovascular problems including low blood pressure, active coronary ischemia and congestive heart failure. Unlike PDE-5 inhibitors, PnPP-19 does not interact with antihypertensives or nitrates, so it can be taken along with these medications. Additionally, it does not require that the patient has intact nitric oxide relaxing nerve fibers and healthy cavernous endothelium, which is another limitation that renders PDE5i medications ineffective. So far PnPP-19 has only been tested on animals but, with the efficacy and safety levels it has demonstrated, it is just the question of time before a clinical study with human participants takes place.
- Natural treatments for ED sow limited effectiveness, few clinical studies on efficacy available - https://www.webmd.com/erectile-dysfunction/features/natural-remedies-for-erectile-dysfunction#1
- Articles by Carolina Nunes da Silva - https://www.researchgate.net/scientific-contributions/2047247186_Carolina_Nunes_da_Silva
- CM Yonamine et al, Blockade of neuronal nitric oxide synthase abolishes the toxic effects of Tx2-5 - https://www.ipen.br/biblioteca/2004/10258.pdf
- CN Silva et al, PnPP-19, A new hope for the treatment of erectile dysfunction - https://www.researchgate.net/publication/305217562_PnPP-19_A_Spider_Toxin_Derivative_New_Hope_for_the_Treatment_of_Sexual_Dysfunction
- CN Silva et al, Treating ED in diabetic and hypotensive animals by intravenous and topical application of PnPP-19 - https://www.jsm.jsexmed.org/article/S1743-6095(19)30005-0/fulltext
- DermaSys transdermal medication delivery system by Futura Medical - https://www.futuramedical.com/content/technology/DermaSys.asp
- CAN Freitas et al, PnPP-19 to treat pain - https://www.mdpi.com/2072-6651/10/1/43/htm