Latest FGF-1 Trial June 2022

[Baron1]

youtube.com/watch?v=C2oUmhO...(Not working as expected?)

[WinnieThePoo]

So 2 participants, no placebo, no blinding, no comment about other medications, different chairs to get out of before and after. Very questionable reference to monkey trial (I think there was 1 monkey in the FGF1 "group").

It's very early days, so looking for improvement is ridiculous, but these videos just seem to show a fairly minimal impact on symptoms (and I suspect there is a swimming pool full of placebo effect - combined with clinician suggestion). The lady still has a pronounced tremor, and the tap test improvements... Nonsense. I have had to do more than my fair share of these for the Biogen trial. The movement requested is as wide and as fast as possible. The "afters" are fast but small movements, and simply would have been "no scores" on my tests. And I improved oceans more than either of them with a half sinemet tablet

I still think these guys might get lucky (and consequently, so might we) , but beyond 2 doses not killing anybody (which is a promising start for safety and tolerability) at this stage it is just an interesting hope.

The more I see of this outfit, the more their "unconventional" methods bother me. As they point out in this video, they have been pursuing fgf1 since Jacobs scraped it off the Merck cutting room floor 23 years ago. They describe their success with coronary heart disease and diabetic foot ulcer. But what is that success? Neither is a clinical treatment yet, and neither appears to have any ongoing product development or clinical trials in progress

What happened to the Mexican PD clinical trial?

I still have my fingers crossed for this one, but having received 4 or 5 updates recently from Zhittya in quick succession, which mostly repeat old ground, this is a fund raising pitch only. And a fairly cheesy one. Nobody in the world of science is going to get on board this.

[WinnieThePoo in reply to WinnieThePoo]

I've found my notes (which I mislaid)

The "research" Dr Jacobs refers to is when he refers to "our research on monkeys"

Primates: de Yebenes JG, Pernaute RS, Garrido JM, Rabano A, Albisua J, Rojo A, Mena MA, Ruiz PG, Jorge P, Correa C, Leenders K, Antonini A, Gunther I, Psylla M and Vontobel P. Long-term intracerebral infusion of fibroblast growth factors restores motility and enhances F-DOPA uptake in parkinsonian monkeys. Parkinsonism Relat Disord 1998; 4: 147-158.

This is the abstract - my emphasis of bold text regarding the "group receiving fgf1". 4 monkeys. 2 placebo controls with no treatment following mptp brain damage. 2 monkeys receiving growth factors. One aFgf (FGF1) and the other bFgf (FGF2). The monkey on fgf2 did better than the monkey on fgf1. That said, whilst they may (shockingly) misrepresent and exagerate this science, the one monkey who received FGF1 made very worthwhile improvements. So possibly dishonest, and misrepresented, but there is hope they can get lucky.

Abstract

Fibroblast growth factors (FGFs) are important for dopamine neurons in health and disease. Acidic (aFGF) and basic (bFGF) fibroblast growth factors increase the survival and growth of dopamine cells. Nigrostriatal dopamine neurons, the target cells for degeneration in Parkinson's disease, display receptors for basic fibroblast growth factor and these receptors are decreased in the brain of parkinsonian patients. We have investigated the effects of long-term intrastriatal infusion of FGFs in hemiparkinsonian monkeys. All animals were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 0.4 mg kg−1, into the left internal carotid artery. The monkeys that had persistent asymmetric akinesia and contralateral rotation induced by apomorphine, were selected for chronic, unilateral, intracerebral infusion of neurotrophic factors or vehicle into the striatum ipsilateral to the lesion. Two animals received intrastriatal aFGF or bFGF, 2 μg week−1, for 6 months. The controls received intrastriatal saline or intraventricular epidermal growth factor (EGF). F-DOPA positron emission tomography scans were performed in each animal before and after the intracerebral infusion of neurotrophic factors. We measured the tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra and terminals in the striatum and evaluated the pathological complications related to the treatment or the delivery system. All four animals had, after the lesion with MPTP, a transient but incomplete recovery of akinesia. This period of spontaneous improvement was followed by a progressive deterioration of motor behaviour during the following months. The monkeys treated with FGFs, however, recovered quickly and persistently during the intracerebral infusion. F-DOPA uptake, prior to the intracerebral infusion, was greatly reduced in the lesioned striatum. The post-infusion F-DOPA scans revealed a 60% reduction respect to baseline in the lesioned striatum of the saline and EGF-infused animals. In the animals infused with FGFs, the post-infusion F-DOPA uptake increased more than 400% in the lesioned (and infused) striatum and around 200–300% in the contralateral side, with respect to the pre-infusion scan. The number of TH-positive cells in the substantia nigra correlated well with the uptake of F-DOPA in the post-infusion scan. No severe side-effects were present. Intrastriatal infusion of FGFs restores motor behaviour and increases F-DOPA striatal uptake in hemiparkinsonian monkeys.

[Baron1 in reply to WinnieThePoo]

I agree, it is all a bit amateurish and the old video that they refer to, is very grainy.

[WinnieThePoo in reply to Baron1]

Still, fingers crossed!

[Bolt_Upright in reply to WinnieThePoo]

Perfectly written! I noticed the chair height also. As Baron1 said, pretty amateurish. But I also think there is a chance they are onto something.

The thing that bothered me is: They are going to these foreign countries that will let them perform trials, but then they say they hope the foreign trials will get the FDA to green light them. Why do they care about the FDA? Just get the drug approved in Kurdistan or Venezuela, or North Korea. I don't mind traveling.

[WinnieThePoo in reply to Bolt_Upright]

They are in it for the money, which is fair enough. They can treat a million people with FDA approval, and I suspect a minimum treatment cost of $25000. I need to check my notes but I estimated their claimed drug COST for each treatment on the trial at $15000. If it's FDA approved it will be covered by insurance in the USA. Free in EuropeAnd if medical complications arise from an unauthorised treatment?

[WinnieThePoo in reply to Bolt_Upright]

And their failure to get FDA approval is due to their failure to do anything remotely properly. If you read their bulletins, as I have been doing for a couple of years now, they state they applied for authorisation to carry out human trials but the FDA require them to do more animal tests firstThey imply they have carried out substantial research (and the fda are therefore being picky).

Actually, they have not carried out ANY research and are faking it with someone else's research from 1998 involving one monkey.

And as far as I'm aware, they are not carrying out any further animal tests and have no plans to.

So they're not going to get the FDA approval started.

I think they are hoping for slam dunk obvious major benefit from their handful of flakey carribean trials, and they will then sell the rights to someone like Merck to develop and take to market.

Meantime, they form more flakey loss-making companies and peddle the hope around small investor fairs raising a few more dollars to keep it rolling on

But I think they are naieve about the level of proof required to get a serious investor on board

Moreover, this growth factor was released by Merck at the beginning of the century and, although I've asked, there is no information forthcoming about a patent. So what are they going to sell?

[WinnieThePoo in reply to Bolt_Upright]

But I should add, for all that, I still think that they might get lucky

[Baron1 in reply to WinnieThePoo]

A genuine trial and for that matter, clinical studies would have a Peer Review of their findings to support or debate the findings,

These clowns are playing on peoples fear.

Why such a small trial, I wouldn't put it past these doctors if the patients in the trial are not friends or paid to appear in the studies to give some credence to the trial.

If this was so explosive in what they have found, don't you think the media would be covering it more and it would be gathering some attention?

However, it has no traction or media following.

[WinnieThePoo in reply to Baron1]

It's unconventional. I think its probably a bit short of fraud though. They have a very odd approach. On the back of some genuine animal testing conducted by Jacobs (Beagles) they managed to get a USA FDA approved trial for their heart treatment. Superficially, it was successful. I can find no explanation for why it then appears to have just stopped.

FGF-1 is a solution looking for a problem. It was developed by Merck, and is fairly well known. The reason I think they may get lucky, and the reason they are on this latest project, is that a few years ago there was a research article (I think from Stanford) suggesting there might be a vascular component to regular Parkinsons disease. Subsequently, brain imaging and other research has been supportive of that idea. The boys at Zhittya found it, and appear to have switched all their attention to PD (although they are now extending that to every brain disorder ever heard of. If they would just focus on PD, they might get lucky)

They are NOT a pharmaceutical research business. They are a venture capital vehicle for small cap investment. They lack patience, expertise, and focus. But they might just have got lucky. The drug is probably safe - and , albeit in just one monkey 25 years ago, it did produce very substantial benefits for an MPTP induced parkinsons recovery.

Then they got lucky twice, with the discovery of the nasal inhalation delivery method

And a third time lucky, discovering they could jump to human trials without any of the boring background research work (including animal testing) by going to the Caribbean. I don't think they are going to flog it to a big pharma on the back of the 2 person trial they have just done, but if they had 50 people with no significant adverse events, and very substantial symptomatic improvement, after say 12-18 months post treatment, then someone might jump in.

And start the FDA approval process. Which would probably take 7 years. Although if the benefits were huge, given human trials, albeit outside the US, have already taken place, and the magnitude of the demand for a treatment, it just might get shortened a bit

If its patentable, and has enough life left on the patent.

I have been having private discussions with a couple of chums on the forum about this for some while, and what I like about "these clowns" is that they are likely to have an answer really quickly. Not a definitive, deliverable, clinical solution, but a binary "works" or "doesn't work enough". Probably within 12 months. I use it as my advent calendar - so there is always something exciting happening, while I wait for other peoples proper research to bear fruit.

And IF it works, it's a non-invasive, simple, one-off treatment.