A new molecule to combat Parkinson's, successfully tested in preclinical studies

This is an English translation from Spanish of a new discovery in Argentina: After a decade of studies, researchers from Conicet, UBA and UNT developed Pegasus, which demonstrated an improvement in the characteristic symptoms of the disease. After a decade of studies, researchers from the National Scientific and Technical Research Council (Conicet), the University of Buenos Aires (UBA) and the National University of Tucumán (UNT) developed a new molecule that demonstrated, in preclinical trials, an improvement in the characteristic symptoms of Parkinson's disease . 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. "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 those neurons or how inhibit neuronal damage,” explained Rosana Chehín, the Conicet researcher who led the research . Chehín, who is also a professor at the UNT and director of the Institute of Applied Molecular and Cellular Medicine (Immca, Conicet-UNT-Siprosa), added: “We went with a group of synthesis chemists from the UBA to see if we could carry out a 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 .” Pegasus or DAD 9 addresses the two main problems of Parkinson's disease: improving symptoms and preventing the progression of neuronal damage. The Pegasus compound is a drug candidate that managed to overcome the preclinical stage. According to experts, the next step is the registration of the development with the Food and Drug Administration (FDA) to obtain authorization to begin clinical trials in humans . As Chehín pointed out, 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. On the other hand, Pegasus has neuroprotective activity and prevents the formation of toxic species of the alpha-synuclein protein, the main cause of the pathology. Dopamine agonists make up a group of medications that have an antiparkinsonian effect because they exert their action by stimulating the dopamine receptors in the brain. On the other hand, levodopa – a drug that has been used for more than 60 years for Parkinson's and that can cause adverse effects – acts in the central nervous system through its transformation into dopamine. "Given that 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," said Chehín. 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. If the human tests are positive, those responsible for the research consider that Pegasus could become an alternative for the treatment of Parkinson's disease and even an option to levodopa. “We have all known people who have suffered from this devastating disease. 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. Organizations must work to facilitate and promote these processes. The exercise of articulating the public and the private is complex, but it is not only necessary, but it is vital and of utmost importance,” said the president of Conicet, Daniel Salamone. Meanwhile, Oscar Varela, specialist at the Carbohydrate Research Center (Cihidecar, Conicet-UBA) and one of the leaders of the research, said: “The development of this molecule, which was designed, synthesized, characterized and evaluated in national laboratories, shows the ability that we Argentinians have to face a problem and be able to reach a satisfactory resolution.” Finally, businessman Claude Burgio, founder of Sky Bio LLC, which made the financial contribution for the development, maintained that Pegasus is a “disruptive and without equivalent” molecule.