Researchers at IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) discovered a novel compound compound, that has got the capacity to became a new medication for the treatment of heart symptoms of brain ailments such as Down syndrome and pneumonia.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="http://dx.doi.org/10.1016/j.chempr.2020.06.017">These results are available in preclinical models where the new chemical ameliorated difficulties in cognitive activities, as well as societal interactions and repetitive behaviours, which are present in neurodevelopmental and neurological disorders.</a></span> Researchers currently aim to develop a dedicated startup company with assistance from interested investors in order to further develop this compound and make it remedy for patients. The research was published in the scientific journal Chem: <span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.cell.com/chem/fulltext/S2451-9294(20)30298-9">https://www.cell.com/chem/fulltext/S2451-9294(20)30298-9</a></span>

These breakthrough findings are caused by a joint effort of 2 Italian research teams directed by Laura Cancedda and Marco De Vivo, at the Istituto Italiano di Tecnologia at Genova (Italy). Laura Cancedda is head of the IIT's Brain Development and Disease Laboratory as Well as an assistant scientist at the Dulbecco Telethon Institute.

<em>This study and exciting results come at a time where neuroscience drug discovery in industry struggles to deliver novel breakthrough classes of effective molecules. As a matter of fact, therapeutic options for most of neurodevelopmental disorders have remained scant, or not highly effective over the last decades. This is mainly due to a poor understanding of the mechanisms underlying these challenging pathological conditions. This discovery follows several years of work on NKCC1 function and inhibition at IIT and will possibly bring us closer to the development of sustainable therapeutics for the treatment of a number of brain disorders"-</em>Laura Cancedda, Head of IIT's Brain Development and Disease Laboratory

The two classes done complementary aspects of the research study: the De Vivo's group designed the new molecules with the aid of computational procedures, and synthetize them where as the Cancedda's laboratory centered on extensive biological evaluations of such compounds. The final outcome reflects the development of a promising chemical compound, that is typically referred in pharmaceutical industry called'drug candidate' due to its potential to be clinical drug from the coming years.

<span style="color: #ff6600;"><a style="color: #ff6600;" href="http://dx.doi.org/10.1016/j.chempr.2020.06.017">Co-first authors of the research article are Annalisa Savardi (Cancedda's Laboratory ) and Marco Borgogno (De Vivo's laboratory ) who worked synergistically to spot the novel compounds and investigate their biological consequences in mental performance of preclinical models of neurodevelopmental disorders.</a></span> These models will be the very first experimental steps to validate the advantages and safety of their newest medication.

Particularly, researchers dedicated to the effect of the molecules onto the protein NKCC1, a very promising target for drugs to treat brain disorders. NKCC1 is actually a transporter of chorine (and other) ions from the mind, and also the correct concentration of such ions is also crucial for brain functioning. In a number of brain ailments such as Down syndrome, autism and epilepsy, the concentration of such growths in the mind is dysregulated as a result of NKCC1 abnormal function. These newly discovered compounds can potently and selectively block NKCC1, without undesired side effects (excess diuresis) due to fact by other existing drugs that are non-selective NKCC1 inhibitors.
"Now, our most promising compound could come right into clinical evaluations at hospitals in less than two years from now. This extra step toward making of this chemical an approved medication, nevertheless, requires further work and more funds. Because of this , we plan to establish a fresh start up company focused on this project. It would be wonderful to see our discovery affecting those in demands" - adds Marco De Vivo.
The newly discovered and promising drug candidate is presently undergoing advanced preclinical studies to move forward and reach soon clinical studies. More studies will enable specifying the general security profile of the molecule and other important parameters, like pharmacokinetics, formulation and dosing, essential to fulfill the regulatory requirements to access clinical studies.
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<span style="color: #ff6600;"><a style="color: #ff6600;" href="https://www.iit.it/" target="_blank" rel="noopener noreferrer">IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology)</a></span>

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Savardi, A., <em>et al.</em> (2020) Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders. <em>Chem<span style="color: #ff6600;">.</span></em><span style="color: #ff6600;"> <a style="color: #ff6600;" href="http://dx.doi.org/10.1016/j.chempr.2020.06.017" target="_blank" rel="noopener noreferrer">doi.org/10.1016/j.chempr.2020.06.017</a>.</span>

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