100% Argentine: they patented a new molec... - Cure Parkinson's
100% Argentine: they patented a new molecule to combat Parkinson's, successfully tested in preclinical studies
What does the article mean by "pre-clinical?" Maybe In Vitro? Maybe not that far along.
Don't they need animal testing first for a new molecule? Here is a quote from the article :
' That something that emerged in a laboratory with many years of quality basic research is transformed into a new molecule, which is then scaled up and taken to final tests – which will take years and more time to reach the market – is a great satisfaction. '
Art
They (intentionally) don't say. "...emerged in a laboratory..." whatever that means.
Anyway, it's an article - meaning some researchers need more $$.
Am I getting cynical in my old age?
We are!
Art
It's a good thing, too. Somebody around here needs to be.
...With good reason it turns out, Via Google Translate:
"Since dopamine cannot be administered alone because it does not pass the blood-brain barrier, we design this molecule that is a carrier that transports dopamine to the brain using the tetracyclines transport system, Chehin said. He added that the new molecule retains the best properties of dopamine and tetracycline: for example, the researchers ruled out the antibiotic function of tetracyclines that, in the long term, generate resistance"
Color me skeptical that a new way of delivering dopamine is going to be disease modifying.
My guess is it's the a-syn stuff that's disease modifying"Chehín indicates that the new molecule acts, on the one hand, as a “ dopamine agonist ”, that is, with a function similar to dopamine, which is an essential neurotransmitter in the brain. While, on the other hand, it presents neuroprotective activity , preventing the formation of toxic species of the alpha-synuclein protein , the main cause of the pathology."
An alternative to levadopa without dyskinesia, on-off fluctuations, or food absorption issues as the other facet obviously is a bonus
I found the study here:
chemistry-europe.onlinelibr...
You are correct about inhibiting α-synuclein aggregation:
"Using the Thioflavin-T assay, we found seven compounds were more effective than doxycycline in inhibiting α-synuclein aggregation. Furthermore, two of these derivatives exhibited better anti-inflammatory effects than doxycycline in a culture system of microglial cells used to model Parkinson's disease neuroinflammatory processes. Overall, through structure-activity relationship studies, we identified two newly designed tetracyclines as promising drug candidates for Parkinson's disease treatment."
discoveries.vanderbilthealt...
This is the only clinical trial for disease modifying/halt progression. Whoever will be around, LUCKY THEM! 
Ah. Not reported in english language (or anywhere outside Argentina. Not "made in America"So not interested!
Well the European membership of this forum finds it interesting
Although obviously the only relevant research is drugs immediately available for delivery today. Fancy having to wait 10 years
Actually, because they have Argentine non-commercial research funding patents in place, scaled up production, and are poised to start fda approved in-human trials and the molecule has a symptomatic mechanism which can be quickly tested in trials, it could be much less than 10 years
But it's not in english in America so it doesn't exist
Thank you for posting Caro-1973
I wonder if this is the same thing:
SKYBO1 is a novel first-in-class and best-in-class new chemical entity, small molecule oral drug that penetrates the brain and initiates an increase in brain dopamine, reduction of brain alpha-synuclein and activation of D1 dopamine receptors.
SKB01 is a novel NCE currently undergoing IND enabling studies for first-in-human (FIH) Phase 1 clinical trials. SKB01 has already demonstrated success in the preclinical toxicity tests. SKB01 molecule is patent approved. The next steps include initiating the FIH Phase 1 studies to determine a maximal tolerated dose in healthy volunteers, before advancing to Phase 2 clinical trials in neurodegeneration.
"With the collaboration of the North American biotechnology company Sky Bio LLC, the experts even managed to patent the molecule in the United States and the European Union. This is Pegasus or DAD 9 , the first molecule capable of addressing the two main problems of Parkinson's disease: improving symptoms and preventing the progression of neuronal damage."
diagnosticsnews.com/noticia...
For 10 years we have been developing studies on the molecular bases of Parkinson's disease, precisely because by understanding what causes the disease, what kills dopaminergic neurons in the pathology, one can find how to protect these neurons or how to inhibit them. neuronal damage , explains Chehín. And he adds: We went with a group of synthesis chemists from the UBA to see if we could carry out an ambitious project that was the synthesis of a molecule, what is known as rational drug design. In simple words, we sought to develop a molecule capable of doing what we wanted. And so we come to Pegasus .
Chehín indicates that the new molecule acts, on the one hand, as a “ dopamine agonist ”, that is, with a function similar to dopamine, which is an essential neurotransmitter in the brain. While, on the other hand, it presents neuroprotective activity , preventing the formation of toxic species of the alpha-synuclein protein , the main cause of the pathology.
The researcher argues: Since dopamine cannot be administered alone because it does not pass the blood-brain barrier, we designed this molecule that is a carrier that transports dopamine to the brain using the tetracycline transport system . And she adds that the molecule retains the best properties of dopamine and tetracycline. For example, they ruled out the antibiotic function of the latter, which, in the long term, generates resistance.
For Chehín, Pegasus, if the human tests are positive, could become an alternative for the treatment of Parkinson's disease. Likewise, it indicates that it could become an option to levodopa, a drug that has been used for more than 60 years for Parkinson's and that can cause adverse effects.
"Pegasus: a novel dopamine agonist with neuroprotective effect
Rosana Chehin, Agustin Pernicone, Verónica Manzano, Esteban Vera Pingitore, Martin Luong, Cesar L. Ávila, Adriana Kolender, Florencia González-Lizárraga, Rodrigo H. Tomas-Grau, Silvina Chaves, Oscar Varela, Diego Ploper
Date / Location: Sunday, 10 July 2022 / S02-748
Add this poster event to your 🗓
Aims: continuous and safe delivery of dopamine across the blood brain barrier (BBB) is a main obstacle for successful substitution therapy in Parkinson's disease. However, the presence of the neurotransmitter does not interfere the progression of neuronal death. Our aim is taking advantage of the well-known capacity of doxycycline (DOXY) to cross the BBB together with its neuroprotective activity to obtain a DOXY-DOPA hybrid molecule that we call Pegasus. Methods: Pegasus was synthetized by removal of the dimethylamino function at C4 and introducing an amino group at C-9, which was covalently linked via a linker to dopamine. Activation of dopaminergic receptors was performed by cAMPNOMAD Cells (Innoprot). Cytotoxicity was studied by MTT assay in SH-SY5Y/Bv2 cell lines. Neuroprotective properties were studied as follows: i) inhibition of α-Synuclein (AS) aggregation by ThT assay; ii) antioxidant capability by CellRoxTM assay; iii) inhibition of proinflammatory cytokine IL-1β release by microglial cells; iv) antiapoptotic properties on HEK293T Cytochrome C-tGFP cell line, and v) influence on lysosomal biogenesis in SH-SY5Y cells with LysoTrakerTM assay. Results and conclusion: Pegasus activated dopaminergic receptors 10-fold less efficiently than dopamine but resulted in improved theoretical ability to cross the BBB. Pegasus did not show toxicity in two different cell lines, and efficiently inhibited AS amyloid aggregation as well as LPS or AS fibrils-induced neuroinflammation. The new molecule also preserved antioxidant properties, characteristic of tetracyclines, and did not interfere with lysosomes biogenesis. We present Pegasus as a dopamine agonist with neuroprotective activity, and an ideal candidate for further preclinical studies."
world-wide.org/fens-22/pega...
Yes. Well done. SC01, pegasus and dad-9 are all the same thing. I have some reservations about the confident assertion that mis-folded a-syn is responsible for the pathology, but I think custom design of molecules is going to be an important development of ever improving therapies and even one day a cure
Gracias Caro. This sounds interesting although very early stage. They will speak with FDA for the first time as a next step.
