Biotechnology seeks solutions for Parkinson's, the second most common neurodegenerative disease

Parkinson's disease (PD) stands as the second most common neurodegenerative disease in industrialized countries after Alzheimer's disease. According to data from the Spanish Society of Neurology, more than seven million people suffer from Parkinson's worldwide. In the case of Spain, approximately 10,000 new cases are detected each year, with a total figure exceeding 150,000 individuals. We're facing a concerning public health issue, as highlighted by the World Health Organization (WHO), as its prevalence has doubled globally in the last 25 years. The WHO has warned that disability and mortality from Parkinson's disease are increasing at a much faster rate than any other neurological disease.

In its early stages, the disease often goes unnoticed as its manifestation consists of prodromal symptoms (depression, sleep-related problems, cognitive deficits, olfactory dysfunction, constipation, and other symptoms related to the autonomic nervous system). As it progresses, patients experience more specific motor symptoms leading to a definitive diagnosis: involuntary or uncontrollable movements, tremors, stiffness, and difficulty with balance and coordination.

Parkinson's is an extremely debilitating disease that has a negative impact on the daily lives of affected individuals and their families. To date, despite the significant efforts made by the scientific community, there is no cure, and we only have medications aimed at alleviating symptoms once the diagnosis is made, such as levodopa and carbidopa (considered first-line drugs for the treatment of Parkinson's motor symptoms). This situation poses significant challenges as, as indicated, its prevalence is expected to increase in the coming years as life expectancy also increases, so it is likely that in the coming years the healthcare system will have to face an economic burden on the order of billions of euros to address this disease.

In this context and on the occasion of World Parkinson's Day celebrated this April 11th, we focus on how biotechnology works with the aim of finding solutions to tackle the public health problem that Parkinson's represents. A promising example is found in the project "Development of new drugs for the treatment of Parkinson's through Artificial Intelligence and massive compound screening," coordinated by AseBio and involving Celtarys Research, ZeClinics, and the Biofarma group of the University of Santiago de Compostela. A project that combines ZeClinics' target validation and in vivo drug screening capabilities, Celtarys Research's scientific knowledge in the design and synthesis of fluorescent tools, and the high-throughput in vitro screening assay development capabilities of USC-Biofarma.

Biotechnology in search of new therapeutic targets against Parkinson's disease

The main objectives of this project consist of identifying new therapeutic targets to treat Parkinson's disease and establishing an effective protocol to identify drug candidates that can modulate these targets. Achieving this objective represents the first milestone of a larger project aimed at identifying a molecule capable of interfering with the disease. With no cure currently available, it is vital to contribute to the search for active molecules capable of acting on the pathology and improving the quality of life of patients.

"Our Biofarma group (USC) leads a work package in which, leveraging our expertise in applied research for early drug discovery and our high-throughput in vitro screening assay development capabilities, the development of the assay for activity on selected targets, the validation of the developed ligands, and the pharmacological evaluation of the agreed compounds will be carried out, generating new candidates for the treatment of Parkinson's disease," explains Mabel Loza, project's IP.

"We are in an early stage of the drug discovery process, in which we have identified a series of targets with therapeutic potential that need to be validated. For this purpose, the zebrafish as an animal model presents an advantage not only economically but also reduces time by allowing high-throughput pharmacological screening following all ethical guidelines. Our contribution is of vital importance because, with no cure currently available, it is crucial to find and validate new biomolecular targets," highlights Jessica García Fernandez, PostDoc Researcher at ZeClinics.

"Celtarys Research, through its conjugation technology, will design an optimal fluorescent tool, which Biofarma will use in screening assays targeting the targets identified by Zeclinics. This collaborative and structured approach has the potential to significantly advance towards the project's goal, thus improving the treatment and quality of life of Parkinson's patients," explains María Majellaro, Chief Scientific Officer of Celtarys Research.

With the achievement of this project, the initial stages of a new drug discovery program for Parkinson's disease will be completed. In this way, through the use of artificial intelligence tools and genetic manipulation, new therapeutic targets will be experimentally validated, whose inhibition will lead to the total or partial rescue of the pathological phenotype previously observed in models. Additionally, the design and synthesis of fluorescent chemical tools for these new targets identified will proceed. Finally, a high-throughput screening assay will be developed to analyze compound libraries to identify new molecules for the treatment of Parkinson's disease.

The potential positive results of this project will enable the obtaining of potential drug candidates and the establishment of a collaborative drug discovery methodology applicable to other diseases as well.