The Holy Grail © Nina Otulakowski June 2022
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In recent months, RxISK has been working closely with Luisa Guerrini in Milan, whose background is in research on regulatory proteins like p 63 and p 53, on which Thalidomide works. This discovery led to excitement a few years ago when it was thought the mechanism through which Thalidomide causes birth defects had finally been found.
Thalidomide also causes sexual dysfunction and suicidality and these effects overlap with the effects of SSRIs, Isotretinoin and Finasteride which also cause the same problems.
Luisa has since been running assays to test what the effects of SSRIs, Isotretinoin and Finasteride are in the systems on which Thalidomide acts. See The Holy Grail.
The answer is that there are overlaps. In the first slide you see a steadily increasing effect of sertraline on ACE2 receptors and on p63, with no effect on Actin which is there as a control. Luisa has found the same effects with Isotretinoin and Finasteride.
In the second slide you see that the effect of sertraline is very visible for up to 12 hours in fact after which ACE2 receptors and p 63 begin to recover.
Finally in the third slide, sertraline has been added in again at 12 hours in some of the plates and not in others and you can see that the recovery continues from 12 to 24 hours in the plates with no extra sertraline but there is an even more comprehensive wipe-out of ACE2 receptors and p 63 with the second dose of sertraline.
Another hugely encouraging sign is that there are very similar results with both Isotretinoin and with Finasteride. Having common effects across all three drug groups suggests we are on the right path and in addition the goal has always been to find an answer for the enduring sexual dysfunctions that all 3 drugs can cause.
There is more good news than this, however. What happens when p 63 is affected like this? The answer in this case appears to be that cells go into a state of suspended animation. They stop dividing. This again appears to be consistent with what happens in the sexual dysfunctions – things stop working.
The next step is to pinpoint exactly why they stop working Have the powerplants in the cells, the mitochondria, been struck by SSRI or finasteride missiles? Or is something else happening?
Do the cells stay in a state of suspended animation or do they die? Do SSRIs, Finasteride and Isotretinoin all behave the same way or are there points at which they diverge? At the moment, Isotretinoin looks the most potent – the most damaging.
There are other fascinating aspects to this. One is p 63 is the gateway to the neuro-epithilium that forms skin and nerves. This is of interest because SSRIs, Isotretinoin and Finasteride all have effects on skin (hair is a part of skin). Their effects on skin in all three cases are more obvious than any brain effects.
This would also fit in with recent indications that at least some people with enduring sexual dysfunctions have a peripheral neuropathy – see Sensory Receptors and Neuropathy. In the case of small fibre neuropathy we are looking at effects on small nerve fibres in skin.
Thalidomide was also famous for causing a peripheral neuropathy – this was what Frances Kelsey in FDA was concerned about when she delayed the licensing of thalidomide in the United States – not birth defects.
There has been great interest in antibodies lately with many people with PSSD in particular getting test results back showing they have antibodies to Muscarinic, Catecholamine and ACE receptors.
It is complicated to work out what is happening here as COVID and the vaccinations for COVID also seem to cause increases in these antibodies and cause peripheral neuropathy and perhaps an enduring sexual dysfunction as well.
Many of those who get antibody tests post COVID or vaccines have had SSRIs prescribed to them, so teasing out what is happening becomes very difficult. It will be important to keep good timelines as to when the problems began and important to see results from some who have had the vaccine but not SSRIs (or tetracycline antibiotics or antihistamines) or those who have PSSD but have not had vaccines or COVID.
We also need some people to get tests done in laboratories other than Cell Trend, where the majority of results have come from so far. We might even need some of those with results from Cell Trend to get tested in other laboratories also and see if we get the same results back.
The reason to mention this is these results are very important and we need to be absolutely sure what we are dealing with.
A paper just out in Nature Medicine introduces a new idea – Metabotypes. It appears we differ in how our metabolisms respond to finasteride – we split into different groups. This raises the possibility that one of these Types underpin suicidality on this drug or enduring sexual dysfunction. At present it is not clear if specific genes underpin these Types or whether it will become possible to pick out those of us who can take finasteride safely and those who should avoid it.
Merck should be interested in this and should help fund research to find answers to these questions but their response is more likely to be the same as the Tobacco Industry – who have put no effort in tracking down who might be able to smoke with impunity as this would likely reduce their market size and also help confirm that finasteride/tobacco has a role in causing certain problems.
A possible treatment for PSSD, PFS, Post Isotretinoin syndromes and Enduring Withdrawal Syndromes has emerged. We are awaiting results of a clinical trial currently in progress to see if a trial in PSSD makes sense. At present the prospects look good.
While this will be welcome news, and it is welcome news, people should not get too hopefuly too quickly. There will be no quick answer from a clinical trial – there never is.
There will be no large drug company behind this trial of an old drug. So getting a trial to happen and rolling anything that works out to people will need support. Keep an eye on RxISK posts for updates.
Equally, there is no large drug company willing to pay the fees to make Luisa Guerrini’s papers open access – and available to everyone with PSSD, PFS and Post-Isotretinoin Syndromes. We welcome all contributions to help support her work which involves having to order specialized antibodies from China.
The funding Luisa has been given at present is for one Post-Doc for a year. When the work began we had no idea that it might develop as well as it has. The good side to the progress made is we have novel findings now being written up and these will hopefully generate wider interest and the involvement of others.