José Aguareles Gorines

October 27, 2022

"Basic and preclinical research must never forget its ultimate goal, which is to understand the natural world and improve the lives of patients, just as clinical science should never forget the basic humility of its origins."

Dr. José Aguareles Gorines holds a degree in Biology from the Universidad Autónoma de Madrid (UAM) and a PhD in Biochemistry and Molecular Biology from the Universidad Complutense de Madrid (UCM) since 2021. Dr. Aguareles began his research career in the field of oncology, conducting research from 2011 to 2014 at the Spanish National Cancer Research Center (CNIO). In 2015, he worked as the technical director of the central microbiological analysis laboratory in the Republic of Angola before focusing his PhD thesis on neurodegenerative diseases in early 2016. Throughout this period, he has published multiple high-impact articles, participated in national and international conferences, and contributed to scientific communications, as well as taught in various undergraduate and master's programs at UCM.

He is currently the coordinator of clinical trials and a scientific advisor in the Internal Medicine Department at the Quirónsalud University Hospital Madrid. During this time, he has actively contributed to and developed research lines related to SARS-CoV-2, primarily focusing on therapeutic approaches in the acute phase and long-term sequelae of COVID-19. As a result of the research conducted by his team, at least five articles have been published in first-quartile journals in the past year, including the Journal of Hematology and Oncology and Annals of Oncology. Additionally, Dr. Aguareles is an associate professor at Antonio de Nebrija University and a collaborator at the European University of Madrid (UEM), where he teaches courses related to scientific methodology and pedagogy.

His current research lines focus on studying antiviral therapies as early treatment for immunocompromised COVID-19 patients with persistent viral replication. Additionally, Dr. Aguareles is part of a team studying the identification of diagnostic biomarkers for patients who develop chronic fatigue syndrome (CFS), postural orthostatic tachycardia syndrome (POTS), and autoimmune dysautonomia resulting from SARS-CoV-2 infection. His team has received funding for this project through the "XIX Research Grants in Health" from the Mutua Madrileña Foundation.

Project Summary and Clinical Relevance

PhD Thesis: Preclinical Development of VCE-003.2: A New Cannabinoid Derivative with Neuroprotective and Neurogenic Potential

Huntington’s disease is a neurodegenerative, hereditary, dominant disorder affecting one in every ten thousand individuals globally. Neurodegeneration or neuronal death is caused by the accumulation of a protein in a brain region known as the striatum, which is responsible for movement coordination. The life expectancy of a newly diagnosed patient ranges from 10 to 30 years, with rapid deterioration of vital functions and quality of life during this period. Currently, Huntington’s disease has no cure or treatment beyond palliative therapies.

This underscores the need to find effective therapies capable of slowing the progression of neurodegeneration. While many research lines are addressing this issue, it is only part of the problem. The primary issue with Huntington’s disease lies in the fact that by the time the disease is diagnosed, the degree of neurodegeneration is often advanced, making it insufficient to only slow disease progression. From this paradigm arises the need to recover damaged tissue, and this is where the concept of neuroregeneration comes into play. Human brain tissue has very limited regenerative capacity on its own, so it is evident that exploring new molecules capable of stimulating this phenomenon is necessary. Cannabinoids, the active compounds in the Cannabis sativa plant, have shown, in general, a bioactive effect on the central nervous system as neuroprotective agents and modulators of neuronal maturation.

Based on these premises, the objectives of Dr. Aguareles’ PhD thesis were to demonstrate the neuroprotective and neuroregenerative capabilities of a new synthetic cannabinoid derivative, VCE-003.2, developed by Vivacell Biotechnology (now Emerald Health Pharmaceuticals).

In this doctoral thesis, the preclinical development of VCE-003.2, a synthetic derivative of cannabigerol that enhances its pharmacological activity in neurons affected by Huntington’s disease, was conducted. Through experimentation in preclinical models, both in vivo and in vitro, it was demonstrated that VCE-003.2 not only protects the striatum from neuronal death but also stimulates neural progenitors and the formation of new neurons capable of recovering tissue damaged by Huntington’s disease.

The findings of this thesis have an immeasurable impact on the clinical field, as they present the first potential drug capable not only of halting disease progression but also of reversing the effects already caused by it. Furthermore, the thesis demonstrated the first evidence of the molecular mechanisms underlying the compound’s mechanism of action, as well as the absence of toxic side effects. These data are of paramount importance for the approval of drugs for human use. Finally, it has been observed that VCE-003.2 is a candidate molecule for oral administration, one of the main limitations in cannabinoid-based therapies, providing a significant advantage for future patient treatment.

The relevance of this evidence is such that the oral formulation of VCE-003.2, known as EHP-102, has received orphan drug designation by the FDA for the treatment of Huntington’s disease.

As Dr. José Aguareles comments, "These types of studies represent a turning point and a paradigm shift in how we perceive the treatment of neurodegenerative diseases. Until now, these diseases were considered incurable, with treatment limited to alleviating symptoms. However, these findings open the door to revisiting an issue that has been intensely debated in recent decades: the regenerative capacity of the central nervous system and its application in treating diseases such as Huntington’s, Parkinson’s, and ALS."