FGF-1 And The Road To The British Virgin Islands: Is It A Cure?

FGF-1 And The Road To The British Virgin Islands: Is It A Cure?

I have tried many different modalities and treatments for my Parkinson's disease, some of them just for the symptoms, and others as an attempt to reverse or stop the progression of the disease. I would like to review these therapies with you so that you will know how better to choose how to spend your money and what would be more or less likely to help you significantly. Only one of the therapies that I have tried seems to have the potential to truly reverse or “cure” the disease. That is human Fibroblast Growth Factor type 1 (FGF1). 

The Basics of FGF

Proteinaceous “fibroblast growth factor” (FGF) activity and Fibroblast Growth Factor Receptors (FGFR) were first identified in 1973. Since then a total of 23 groups of FGFs and FGFRs have been identified. These are naturally occurring human molecules that have important biological activity.

*After Ornitz and Itoh. New developments in the biology of fibroblast growth factors.

Current Research on FGF1

Unfortunately, few studies have been done on these interesting molecules, and most efforts have been focused on the development of pharmaceuticals that indirectly or directly act on the growth factor or its receptors rather than the factor itself as a therapeutic agent.

Regulated fibroblast growth factor (FGF) signaling is a prerequisite for the correct development and homeostasis of joint cartilage, as evidenced by the fact that aberrant FGF signaling contributes to the maldevelopment of joints and to the onset and progression of osteoarthritis.

Recently, FGF-1 has emerged as a key regulator of bile acid, lipid, and carbohydrate metabolism, and therefore as a potential therapy for hyperlipidemia, coronary artery disease, peripheral arterial disease, diabetes mellitus type 2, and bile acid disorders such as steatohepatitis and non-alcoholic fatty liver disease (NAFLD).

FGF-1 is one of the best-characterized members of the FGF superfamily. FGF-1 is a powerful mitogen (a small bioactive protein or peptide that induces a cell to begin cell division or enhances the rate of division (mitosis), exhibiting strong action on numerous different cell types.) It is known that FGF1 is both angiogenic (stimulates the formation of new blood vessels) and neurogenic (stimulates the generation of new neurons). It plays a role in various stages of development and morphogenesis, as well as in angiogenesis and wound healing processes. The engineering of FGF’s can bring many advantages. Additionally, the application of FGF’s as recombinant polypeptides in the treatment of wound and fracture healing, cardiovascular diseases, and neurodegenerative diseases seems to be a rational medical approach. Despite the concerns that the angiogenic actions of FGF’s could have adverse effects on internal organs and new vessel growth in such things as tumors, to date there have been zero such effects. In fact, FGF1 has been noted to reduce inflammation and oxidative stress, repair the blood-brain barrier (BBB), suppress excitotoxicity, and improve insulin sensitivity. This has powerful implications for FGF1 as a therapeutic agent for multiple dementias, including Alzheimer’s disease, vascular dementia, multiinfarct dementia, and Lewy Body disease.

Enter Zhittya

Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for the Merck Group, founded in Germany in 1668, of which it was once the American arm. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. It is one of the largest pharmaceutical companies in the world, ranking number 2 by revenue as of 2023.

FGF-1 was discovered in the 1970’s and Merck tried to commercialize human FGF-1. They were not successful, and in 1998, the owner of Zhittya Genesis Medicine (ZGM) purchased the patent for the manufacture of FGF-1 from Merck in 1998, and ZGM has been trying to develop it for the treatment of diseases that have a vascular etiology. They list 19 diseases in this category, and Parkinson’s disease of one of them.

In September of 2023 while doing some internet searches for treatment of Parkinson’s disease, I came across the ZGM website (zgm.care), and I watched the videos about their studies with rats and monkeys using intravenous recombinant DNA-based/manufactured FGF-1, and I was very impressed with the results. Subsequently, they discovered that intranasal administration of the FGF-1 product was much better at delivering the FGF-1 to the brain. They have another website on which they offer compassionate treatment via medical research trials (specifically trials of intranasal FGF-1 to establish the dosing regimen/protocol, effectiveness, and identify side effects) to patients with Parkinson's who meet their inclusion criteria. I applied (which consisted of filling out an online application and an online video conference with one of the company’s subject evaluators) and was accepted for the medical research trial. The big drawback and, for many people, a big red flag was the requirement that participants pay $50,000 to receive the medicine!  Almost nowhere in the research of drugs are participants asked to pay for the drug or to be admitted to a trial. It is universally considered to be a sign of fraud or a scam of some kind.

The owner of ZGM has spent over 150 million dollars so far toward developing the FGF-1 as a drug therapy for Parkinson’s and for several other diseases, purported to be arising from a disease of vascular deficiency origin.

Going for the Medicine

In reviewing the studies ZGM has done, I was impressed especially with the monkey studies. I weighed the findings of the studies and anecdotal stories of nearly 100 people with Parkinson’s who have been receiving the medicine and made a leap of hope to try and raise the money for this treatment.  With that in mind, my dear friend Rhianne Newlahnd started a GoFundMe campaign, and Dr. Victoria Coulter put together a fundraising gathering and art sale with the help of many other people. Thanks to everyone who donated and participated.

It cost about $70,000 to do in total because I needed to pay for people to take me down there and care for me. It took three people to get me down there and back (my Angels, Victoria, my caregiver Jaime, and her husband Caleb).  I was almost in a wheelchair at that time, and I was for most of the trip. We went down to Tortola in the British Virgin Islands and met the people from the drug company. They gave a lot of pep talks about the drug and showed us all how to use the drug properly, about possible side effects (there have been a few minor side effects, but nothing of significance). I used it for five days, twice a day during the week that I was there. I did see people improve, and that was remarkable. In fact, I had regained my sense of smell from another therapy that I was doing, but it got even better, and my libido and vitality were also stronger, so I thought the drug had an immediate effect. Since then, I’ve taken the drug for three days twice a day every three weeks. I’ve noted afterwards that I start to feel and function better, and that’ll last for a few days, and then it's back to being so fatigued that I can’t do as much. May 19th is my next round (20th round). I definitely feel better during and for a few days after the drug treatment. Then I just slowly go down in energy again. It's frustrating.

Improvements?

There are 200 people with Parkinson's doing this medical research trial now. The reports from participants are varied. Some say they are 85% better, but most say 0-25% better. I've done this for a year and three months now. I report to an RN by Zoom every 3 months. I report on my progress, blood pressure, and other vital signs, perform certain tasks, and talk about my cognitive function.  

I’ve tried to do a crossword puzzle every day. I’m getting pretty good at it. I try to read, but I don’t have enough energy most of the time. I try to play the guitar and piano; it’s difficult to do for very long if I can at all. Most days I lie around, try to get up, and do some exercise.  I get anxious and depressed when I am not very functional, especially after being normal for a few ½ days, which does happen, and I believe is an indicator of improving function in response to the medication. Sometimes my voice just “goes away”, and it’s hard to do anything.  If you take into consideration that I was on a negative exponential curve at the time when I started the FGF-1, and that I’ve had the disease for 21 years, and was in advanced stage three(out of 4 stages, where dysfunction is slowly progressive, until it reaches the later part of stage 3 and that I’m some better, and that I’m not I’m not exactly getting worse, it’s truthful to say the medicine is having positive effects.  I believe that the FGF-1 has slowed the progress of the disease.

It’s my theory that the periods of normal function (with absence of any symptoms of disease) are a behavior of the cosine wave pattern of the phenomenon with rising Y values. This produces intermediate states where there are specific times when the observed clinical improvements are continuously manifest, times during which they are intermittently manifest, other times when they are not.  

In summary, the FGF-1 appears to be improving my clinical status with regard to the Parkinson’s, but it will take more time to be sure. I remain optimistic. I have improved function overall; I would say about 15-20%.

The other people in my cohort of 10 people are not very responsive and basically do not communicate about their status. There is a Facebook page for the cohort, but no one posts. There are a few people who text each other via a group text, but I’ve found it is not useful, as the majority of their posts are religious pep talks.

The following is a list of symptoms that I had prior to beginning the FGF-1 and indicators of how this has changed or not.

1.      Left upper extremity tremor and dyskinesia: vastly improved, but it does happen in early AM after awakening; goes away after a very few minutes.

2.      Bradykinesia (slow motion and getting stuck): Happens with some regularity on a daily basis, and has slowly become less frequent.

3.      Loss of left arm swing: Nearly gone.

4.      Cogwheeling rigidity: None.

5.      Gait instability: Happens when there is bradykinesia. I get what I call being “Parky”

6.      General debilitating fatigue: Continues to be the biggest problem, but appears to be improving. I took valaciclovir for 2 months for what appears to be a reactivated Epstein-Barr Virus infection (based on lab results). I think that helped a little with the fatigue, but it’s difficult to say. I also took a supplement treatment regimen for long-COVID (hard to test for) for 3 months, and there was little to no improvement in the fatigue.

7.      Loss of smell sensation: This has improved significantly, is intermittent, and appears to have responded first to the use of infrared (NIR) and red-light therapy.  

8.      Constipation: Improved.

9.      Urine retention: Resolved!

10. Orthostatic hypotension: Still having this but is slowly improving with all the other autonomic nervous system dysfunctions.

11. Nocturnal clonic leg jerking: very uncomfortable/painful and used to last 5-6 hours. Now it occurs once or twice a week for only 1-2 hours, is less intense, and is terminated with low-dose alprazolam and/or low-dose baclofen.

12. Dysphonia: Intermittent and improving slowly.

References

Ornitz DM, Itoh N. New developments in the biology of fibroblast growth factors. WIREs Mech Dis. 2022 Jul;14(4):e1549. doi: 10.1002/wsbm.1549. Epub 2022 Feb 9. PMID: 35142107; PMCID: PMC10115509.

Xie Y, Zinkle A, Chen L, Mohammadi M. Fibroblast growth factor signalling in osteoarthritis and cartilage repair. Nat Rev Rheumatol. 2020 Oct;16(10):547-564. doi: 10.1038/s41584-020-0469-2. Epub 2020 Aug 17. PMID: 32807927.

Struik D, Dommerholt MB, Jonker JW. Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application. Curr Opin Lipidol. 2019 Jun;30(3):235-243. doi: 10.1097/MOL.0000000000000599. PMID: 30893110; PMCID: PMC6530965.

Liu Y, Liu Y, Deng J, Li W, Nie X. Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects. Front Endocrinol (Lausanne). 2021 Oct 14;12:744868. doi: 10.3389/fendo.2021.744868. PMID: 34721299; PMCID: PMC8551859.

Suh JM, Jonker JW, Ahmadian M, Goetz R, Lackey D, Osborn O, Huang Z, Liu W, Yoshihara E, van Dijk TH, Havinga R, Fan W, Yin YQ, Yu RT, Liddle C, Atkins AR, Olefsky JM, Mohammadi M, Downes M, Evans RM. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature. 2014 Sep 18;513(7518):436-9. doi: 10.1038/nature13540. Epub 2014 Jul 16. Erratum in: Nature. 2015 Apr 16;520(7547):388. doi: 10.1038/nature14304. PMID: 25043058; PMCID: PMC4184286.

Huang Z, Tan Y, Gu J, Liu Y, Song L, Niu J, Zhao L, Srinivasan L, Lin Q, Deng J, Li Y, Conklin DJ, Neubert TA, Cai L, Li X, Mohammadi M. Uncoupling the Mitogenic and Metabolic Functions of FGF1 by Tuning FGF1-FGF Receptor Dimer Stability. Cell Rep. 2017 Aug 15;20(7):1717-1728. doi: 10.1016/j.celrep.2017.06.063. PMID: 28813681; PMCID: PMC5821125.

Scarlett JM, Rojas JM, Matsen ME, Kaiyala KJ, Stefanovski D, Bergman RN, Nguyen HT, Dorfman MD, Lantier L, Wasserman DH, Mirzadeh Z, Unterman TG, Morton GJ, Schwartz MW. Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents. Nat Med. 2016 Jul;22(7):800-6. doi: 10.1038/nm.4101. Epub 2016 May 23. PMID: 27213816; PMCID: PMC4938755.

Scarlett JM, Muta K, Brown JM, Rojas JM, Matsen ME, Acharya NK, Secher A, Ingvorsen C, Jorgensen R, Høeg-Jensen T, Stefanovski D, Bergman RN, Piccinini F, Kaiyala KJ, Shiota M, Morton GJ, Schwartz MW. Peripheral Mechanisms Mediating the Sustained Antidiabetic Action of FGF1 in the Brain. Diabetes. 2019 Mar;68(3):654-664. doi: 10.2337/db18-0498. Epub 2018 Dec 6. PMID: 30523024; PMCID: PMC6385755.

Liu W, Struik D, Nies VJ, Jurdzinski A, Harkema L, de Bruin A, Verkade HJ, Downes M, Evans RM, van Zutphen T, Jonker JW. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2288-93. doi: 10.1073/pnas.1525093113. Epub 2016

Liu W, Struik D, Nies VJ, Jurdzinski A, Harkema L, de Bruin A, Verkade HJ, Downes M, Evans RM, van Zutphen T, Jonker JW. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2288-93. doi: 10.1073/pnas.1525093113. Epub 2016 Feb 8. PMID: 26858440; PMCID: PMC4776526.eb 8. PMID: 26858440; PMCID: PMC4776526.

Farooq M, Khan AW, Kim MS, Choi S. The Role of Fibroblast Growth Factor (FGF) Signaling in Tissue Repair and Regeneration. Cells. 2021 Nov 19;10(11):3242. doi: 10.3390/cells10113242. PMID: 34831463; PMCID: PMC8622657.

Liu Y, Liu Y, Deng J, Li W, Nie X. Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects. Front Endocrinol (Lausanne). 2021 Oct 14;12:744868. doi: 10.3389/fendo.2021.744868. PMID: 34721299; PMCID: PMC8551859.

Hutley L, Shurety W, Newell F, McGeary R, Pelton N, Grant J, Herington A, Cameron D, Whitehead J, Prins J. Fibroblast growth factor 1: a key regulator of human adipogenesis. Diabetes. 2004 Dec;53(12):3097-106. doi: 10.2337/diabetes.53.12.3097. PMID: 15561939.

Comerota AJ, Throm RC, Miller KA, Henry T, Chronos N, Laird J, Sequeira R, Kent CK, Bacchetta M, Goldman C, Salenius JP, Schmieder FA, Pilsudski R. Naked plasmid DNA encoding fibroblast growth factor type 1 for the treatment of end-stage unreconstructible lower extremity ischemia: preliminary results of a phase I trial. J Vasc Surg. 2002 May;35(5):930-6. doi: 10.1067/mva.2002.123677. PMID: 12021709.

Zakrzewska M, Marcinkowska E, Wiedlocha A. FGF-1: from biology through engineering to potential medical applications. Crit Rev Clin Lab Sci. 2008;45(1):91-135. doi: 10.1080/10408360701713120. PMID: 18293181.

Matkar PN, Ariyagunarajah R, Leong-Poi H, Singh KK. Friends Turned Foes: Angiogenic Growth Factors beyond Angiogenesis. Biomolecules. 2017 Oct 2;7(4):74. doi: 10.3390/biom7040074. PMID: 28974056; PMCID: PMC5745456.

Zhai W, Zhang T, Jin Y, Huang S, Xu M, Pan J. The fibroblast growth factor system in cognitive disorders and dementia. Front Neurosci. 2023 May 5;17:1136266. doi: 10.3389/fnins.2023.1136266. PMID: 37214403; PMCID: PMC10196031.

Liu A et al. https://www.fiercepharma.com/special-reports/top-10-most-profitable-pharma-companies-2021. The top profitable pharmaceutical companies in 2021

The 50 largest pharmaceutical companies in the world". "Drug Discovery Trends 2023-50 Largest Pharma Companies 

FreedomFest 2022: First In-Human Research Studies for Parkinson's Disease- Dr. Jack Jacobs