April 27, 2021 at 1:44 pm #20606Dan MontanoParticipant
Zhittya Genesis Medicine, has obtained regulatory clearance to start the First in Humans Proof of Concept-Phase I clinical trial. Zhittya was delayed by the COVID-19 pandemic shut downs, however in April 2021 announced it now has a regulatory pathway to proceed. Daniel Montano-CEO-Zhittya Genesis Medicine stated “we hope by the end of 2021 to know if our medicine is safe in the brain of Parkinson’s suffers and if there is any improvements in their condition. In monkey trials, our molecule FGF-1 reversed Parkinson’s Disease. We will now test FGF-1 in humans and see if we have a treatment.”
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- This topic was modified 1 month, 4 weeks ago by Dan Montano.
April 28, 2021 at 9:26 am #20617
Hi, this is Dr. Jack Jacobs and I will be supervising Zhittya Genesis Medicine’s upcoming clinical trial in patients with Parkinson’s disease. We will be testing a growth factor, human FGF-1, which has shown promise in animal models of Parkinson’s disease (rodent and primate). We will test three ascending doses of the growth factor which will be administered intravenously. Please go to our website at zgm.care to learn more about the trials. I am also excited to report that we will also be seeing if our drug delivered intranasally can enter the brain and may represent a much less invasive way to administer our drug. I will talk more about that on a future Forum post!
April 28, 2021 at 10:12 am #20620Bill ChurchParticipant
Good morning….Is the ‘proof of concept’ study using monkeys published and if so could you please provide the reference.
April 28, 2021 at 4:22 pm #20624
Here are two references where the angiogenesis growth factor we are developing, human FGF-1, reversed motor disabilities and regenerated new dopamine-secreting neurons in the substantia nigra region of the brain in both rodents and primates.
Rodents: Wei X, S He, Z Wang, J Wu, J Zhang, et. al. Fibroblast growth factor 1 attenuates 6-hydroxydopamine-induced neurotoxicity: an in vitro and in vivo investigation in experimental models of Parkinson’s disease. Am J Transl Res 2014;6:664-677.
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.
April 29, 2021 at 3:23 pm #20630PaulParticipant
Didn’t Zhittya Genesis start testing on humans in Mexico more than a year ago? I assume if there was any good news we would have heard about it by now.
April 29, 2021 at 6:18 pm #20636
Yes, we were approved to start testing in humans in Mexico in Feb 2020 and a month later, the world shut down. It has been very frustrating for us and the patients who are following us the delays we have had to bear because of the pandemic. The good news is we now have confidence that the studies will initiate in the June/July 2021 timeframe in Monterrey and that we will hopefully have results by year end.
May 1, 2021 at 4:17 pm #20641
<p style=”text-align: center;”>Vascular Dysfunction in the Brain as an Initiating Event in Parkinson’s Disease</p>
The concept that Parkinson’s disease is essentially a vascular dysfunction disorder comes from the pioneering work of Dr. Berislav Zlokovic and his research team at the Keck School of Medicine at the University of Southern California. These USC researchers believe that a substantial proportion of neurogenerative diseases are wholly or partly due to age-related small vessel disease of the brain.
Here is a quote from one of Dr. Zlokovic’s papers published in the prestigious peer-reviewed journal, Cell: “aberrant angiogenesis, vessel regression, brain hypo-perfusion, and inﬂammatory responses, may initiate and/or contribute to a ‘vicious circle’ of the disease process, resulting in progressive synaptic and neuronal dysfunction and loss in disorders such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple sclerosis, and others.” (Cell, vol 163, pp 1064-1078, November 19, 2015).
It is known that the brain is critically dependent on healthy blood vessels to support the nourishment of its neurons, as well as to remove toxic waste products from the organ. When blood vessels start to work improperly due to age, disease or other factors, the brain’s function can be compromised. If vascular dysfunction occurs in the substantia nigra region of the brain that houses the dopamine-secreting neurons, it is our belief that this is the initiating event in Parkinson’s disease. In my next post, I will review the evidence for reduced blood flow and hypo-perfusion in the brains of patients with Parkinson’s disease.
May 7, 2021 at 3:25 pm #20662
Functional MRI Brain Imaging Shows Reduced Blood Flow with Parkinson’s Disease
In my last post, I discussed a growing body of research that points to vascular dysfunction as an initiating event in Parkinson’s disease. The concept is that reduced blood perfusion in the region of the brain housing dopamine-secreting neurons “chokes off” these neurons from proper nourishment and metabolic waste product removal, leading to decline, hibernation and eventual death of the neuron.
The substantia nigra region of the brain is relatively small, comprising only approximately 500,000 dopamine-producing neurons. In spite of this, the newly evolving imaging technique of functional MRI can, in real time, give information on actual blood flow or perfusion rates in the substantia nigra region of the brain. In a recent study, blood flow was assessed in healthy 21 and 65 year olds, as well as in patients who had Parkinson’s disease or had suffered a stroke affecting that region of the brain. Data from that study documented a dramatic 50% reduction in blood flow in the substantia nigra region in Parkinson’s disease patients when compared to healthy 21 year olds. In healthy 65 year olds, there was an approximate 25% reduction in blood flow in this area of the brain, which is in agreement with many studies coming out now that as we age, blood flow in many areas of the brain begins decreasing, but not to the levels seen in such disorders as Parkinson’s disease.
We believe that “therapeutic angiogenesis” or the stimulation of new blood vessel growth by a biological drug can be successfully utilized to overcome this lack of blood flow in patients with Parkinson’s disease. Zhittya Genesis Medicine Inc. (Zhittya) is developing a biological growth factor, FGF-1, that is probably the most potent inducer of therapeutic angiogenesis yet discovered. Outside of the brain it has already shown great promise in US FDA-authorized clinical trials in treating a number of medical disorders characterized by a lack of blood perfusion, including coronary artery disease, diabetic foot ulcers and venous leg ulcers.
In my next post, I will talk about the design of the clinical trial we will be initiating soon on testing 3 escalating doses of FGF-1 in patients with idiopathic Parkinson’s disease.
May 13, 2021 at 3:47 pm #20688
Phase I “Proof of Concept” Clinical Trial to Test if Therapeutic Angiogenesis with FGF-1 Can Alter the Progression of Parkinson’s Disease
As I have reported in this Forum previously, we are developing a potent angiogenesis growth factor which stimulates the growth of new blood vessels in “ischemic” tissues that are undernourished due to a lack of blood perfusion. We and other medical researchers believe that a lack of blood flow or perfusion to the region of the brain housing dopamine-secreting neurons is an initiating event in Parkinson’s disease and leads to the disease’s progression. In both rodent and primate models of Parkinson’s disease, FGF-1 was able to regenerate new dopamine-secreting neurons in the brains of those animals and reverse motor skill decline. With this data we have been cleared to start our first human study and I will briefly outline below the design of this “Proof of Concept” clinical trial.
Patients with mild to moderately severe Parkinson’s disease will be sequentially enrolled in three ascending dosage groups. We will first enroll patients in the lowest dosing group and measure safety and efficacy before proceeding onto the next higher dosing groups. There is no placebo group in this first study and all patients will receive 1 hour intravenous infusions of FGF-1 five days a week for four weeks. For ease of drug administration and blood draws for laboratory testing, enrolled patients will have a central PICC line placed in their arms for the 4 week treatment period. Safety and effectiveness will be monitored throughout the study with the final follow-up visit occurring at 52 weeks. Of note, we estimate that the third or highest dosing group will be receiving a dose that is roughly equivalent to what the monkeys received in the successful preclinical animal trial.
We are excited at initiating this study in the next several months. The study will be carried out at the Zambrano Hospital in Monterrey, Mexico and Zambrano is recognized as one of the premier hospitals in Latin America. Our neurologist on site in Monterrey has informed us that they will most likely have all of the volunteers needed for the Phase I trial from the pool of Parkinson’s disease patients that reside in the greater Monterrey area. This first “Proof of Concept” trial was designed as a relatively small study and as we advance into the larger Phase II clinical trials, we will enroll larger numbers of patients at multiple clinical trial sites. I will keep you posted as we advance on this study.
May 20, 2021 at 5:55 pm #20732
I am often asked how do we know if any of our FGF-1 therapeutic angiogenesis growth factor (a factor that stimulates the growth of new blood vessels) will make it into the brain of a Parkinson’s disease sufferer after intravenous delivery? FGF-1 is a large protein and large proteins do not usually make it through the blood-brain barrier, a barrier that protects the brain from noxious and infectious substances that may appear in the blood circulation.
As we are delivering FGF-1 intravenously in our first clinical trial that will get underway soon, we need to rely on previous animal studies that can shed light on this question. We do know that when FGF-1 is administered intravenously in experimental animal models of Parkinson’s disease it successfully regenerated dopamine-secreting neurons in the brains of those animals and restored motor function in those animals to near normal levels.
If we dig a little deeper we can find a good explanation for how FGF-1 gets into the brain from the blood circulation. If you make FGF-1 radioactive and then give it to an animal intravenously you can trace FGF-1’s journey through the body and researchers showed that between 0.5 – 4.0% of the IV dose successfully crossed the blood brain barrier and made it into the brain. It turns out that if you look closely at the blood brain barrier it has developed a very specialized way to get FGF-1 across the barrier. Specific receptors for FGF-1 bind to the growth factor and actually ferry or transport FGF-1 across this barrier. A similar system has also been seen with transport of insulin across the blood brain barrier.
Our brains are smarter than we think! They have developed very sophisticated mechanisms to selectively allow access for molecules, such as FGF-1 and insulin, that are important for its proper functioning.
May 28, 2021 at 7:07 am #20811MichaelParticipant
Hello Dr. Jacobs my question is When do you think this treatment will be available to all Parkinson’s patients such as myself? Thanks for taking my question!
May 30, 2021 at 12:25 pm #20819
Thank you for your question and your interest in our clinical development efforts. As I am sure you appreciate, new drug development can be a painfully slow process and we are trying hard to speed things up as much as possible. For this reasons, we are seeking drug approvals for our medicine not only in the US, but also in foreign countries. We hope to get underway in Mexico in a few months and also have clinical trial submissions under review in the US, Europe and even in Morocco! Whenever and wherever we get the “green light” to start treating patients, we will.
Concerning when the treatment may be available to Parkinson’s patients like yourself, we obviously do not have a crystal ball to predict the outcome of our clinical trials, but if the studies in Mexico proceed smoothly and show our drug is safe and effective in Parkinson’s patients (as was shown in a primate model of Parkinson’s disease), I believe we could see an approval there in as soon as 18 months. Once approved in Mexico, through joint international treaties, it could then also become available in a host of other countries. Although the US has signed such a treaty with Mexico and Canada, I believe the US would still require additional US clinical trials before they approved our drug. However, there is nothing to stop patients from traveling to Mexico to be treated there. I have visited the hospital in Monterrey, Mexico where our clinical trials will be carried out and I can report that it is a large, modern facility that is superbly equipped and staffed with highly trained professional caregivers.
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