New substance to combat Parkinson’s disease

Scientists developed a new chemical substance that has demonstrated, through preclinical trials, an improvement in the characteristic symptoms of Parkinson’s disease and important neuroprotective activity.

The achievement is the work of researchers from the National Scientific and Technical Research Council (CONICET), the National University of Tucumán (UNT) and the University of Buenos Aires (UBA), in Argentina, with the collaboration of the private sector (the North American biotechnology company Sky Bio LLC).

The substance was patented in the United States and the European Union and the research work has been accepted by a renowned academic journal for publication.

The compound is called Pegasus, or DAD 9, and it is the first substance capable of addressing the two main challenges of Parkinson’s disease: mitigating symptoms and preventing the progression of neuronal damage. The compound is a drug candidate that managed to overcome the preclinical stage. The next step is the registration of the development with the Food and Drug Administration (FDA) of the United States, to obtain authorization to begin clinical trials in humans.

Rosana Chehín, CONICET researcher, UNT professor and director of the Institute of Applied Molecular and Cellular Medicine (IMMCA, CONICET, UNT and SIPROSA), leads the research. She is accompanied by a group specialized in chemical synthesis from the University of Buenos Aires (UBA), led by Oscar Varela. The development is the result of the synergy between the public and private sectors, since it has the financial contribution of Sky Bio LLC, a North American biotechnology company founded by businessman Claude Burgio.

Rosana Chehín (center) with the rest of the research team from the Institute of Applied Molecular and Cellular Medicine (IMMCA). (Photo: IMMCA / CONICET)

“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 to inhibit 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 arrive at Pegasus.”

Chehín indicates that the new substance 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: “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.” 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.

In Chehín’s opinion, Pegasus, if the human tests are positive, could become an alternative for the treatment of Parkinson’s disease. Likewise, he indicates that it could become an option to levodopa, a drug that has been used for more than 60 years against Parkinson’s Disease and that can cause adverse effects.

The research team is made up of: Rosana Chehín, Oscar Varela, César Ávila, Benjamín Socías, Diego Ploper, Esteban Vera Pingitore, Silvina Chaves, Verónica Manzano, Rodrigo Tomas Grau, Florencia González Lizárraga, Adriana Kolender and Agustín Pernicone. (Source: CONICET. CC BY 2.5 AR)