For the second time in its history, the Dr. Antoni Esteve Foundation Research Award has finally gone to two works. The international tribunal that awards this award every two years has considered them as the two best pharmacological research articles published by Spanish authors. The prize, of 18,000 euros, has been divided between the Centre for Animal Biotechnology and Gene Therapy of the Autonomous University of Barcelona and the Neuropharmacology Laboratory to thePompeu Fabra University.
The first of the award-winning papers, published in 2013 in the Journal of Clinical Investigation by Arnau Busquets as first author, describes a gene therapy treatment that has managed to cure Sanfilippo syndrome type A in animal models, a rare disease that affects between one and nine out of every 100,000 children. It is a neurodegeneration caused by mutations in the gene that codes for the enzyme sulfamidase and that causes mental retardation, aggressiveness, hyperactivity, sleep disturbances, loss of speech and motor coordination. Children born with this mutation are diagnosed from the age of 4 or 5 and die in adolescence.
The research awarded ex aequo by the Dr. Antoni Esteve Foundation has developed a gene therapy treatment that cures this disease in animal models, with preclinical studies in mice and dogs. The treatment consists of a single surgical intervention session in which an adeno-associated viral vector is introduced into the cerebrospinal fluid, the fluid that surrounds the brain and spinal cord. The virus, which is absolutely harmless, genetically modifies brain and bone marrow cells to produce sulfamidase, and is distributed to other parts of the body such as the liver, from where it also induces the production of the enzyme. Thanks to this intervention, the animal’s behaviour returns to normal and its life expectancy is extended to normal levels.
The work Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy,opens a new avenue to develop gene therapy products for the treatment of other rare neurodegenerative diseases.
The other half of the Dr. Antoni Esteve Foundation award also goes to research into rare diseases, in this case fragile X syndrome (FXS). It is the most common hereditary form of intellectual disability and autism. The UPF Neuropharmacology Laboratory receives this scientific award for the second time, this time to demonstrate that the endocannabinoid system is a new therapeutic target of great interest in the treatment of this disease. A finding that was published in the prestigious journal Nature Medicine in 2013 with Virginia Haurigot as first author.
FXS results from an expansion in the promoter of the FMR1 gene that causes the silencing and loss of the fragile X mental retardation protein (FMRP). Patients with FXS have varying degrees of intellectual disability, attention deficit, anxiety, self-injurious behavior, autistic behavior, macroorchidism, facial anomalies, and a higher incidence of seizures. The disease affects one in 4,000 men and one in 6,000-8,000 women.
The research Targeting the endocannabinoid system in the treatment of fragile X syndrome has reproduced many of the symptoms of FXS in humans in mice and shows that cannabinoid receptors play a key role in the pathophysiology of the disease. The current absence of treatment for this disease increases the interest in being able to validate the relevance of this new therapeutic strategy in the immediate future.
The jury of the Dr. Antoni Esteve Foundation Research Award also wanted to highlight with an Honorable Mention article Critical role of the death receptor pathway in the antitumoral effects induced by hispanolone derivatives, which he published in 2012 in the magazineOncogenea team from the Faculty of Pharmacy of the Complutense University of Madrid and the Inflammation and Cancer Unit of the National Center for Microbiology.
The Dr. Antoni Esteve Foundation Research Award was awarded on 23 June 2015 at a joint event held at the Faculty of Veterinary Medicine of the Universitat Autònoma de Barcelona with the presence of the two award-winning authors and the directors of their respective centres, together with the Vice-Rector for Strategic Projects and Planning of the UAB. This is the fourteenth edition of the award, which is awarded every two years to the best work in pharmacological research published by a Spanish author in a scientific journal during the two years prior to the call in any of its aspects (design, synthesis, galenic development, clinical or laboratory evaluation, use, etc.).
KEYWORDS | Basic pharmacology, rare diseases, research award