Small molecules with a big impact on nervous system disorders

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Research

Pathologies such as autism spectrum disorders (ASD) and Alzheimer’s disease (AD) are common types of synaptopathies, as they are caused by an imbalance in the normal functioning of synapses between nerve cells. It has been shown that the interaction between the neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor Ric8a regulates synapse number and function. This means that designing drugs that enhance or inhibit this interaction is a viable strategy to treat a wide range of synaptopathies, easing the social and economic burden they represent.

Aim

  • To carry out a preclinical proof of concept and produce a valorisation plan for synapse modulators targeting NCS-1/Ric8a as a new therapeutic approach for ASD and neurodegenerative diseases such as AD.

Problem to Solve

48 million people around the world have some form of autism, and there are 50 million people with dementia (including AD). Both are disorders with a great impact on patient quality of life, as well as the living conditions of their families. In economic terms, the costs per year for children with ASD in the USA were estimated to be around 175 billion dollars. In the case of dementia, the current estimated cost worldwide is around 800 billion euros per year.

Nowadays, neither AD nor ASD have a cure, and existing drugs mainly target their symptoms, rather than the aetiology of the diseases.

Innovation

Two families of compounds have been developed. First, a group of compounds that inhibit NCS-1/Ric8a binding, targeting synaptopathies caused by an excessive number of synapses, such as ASD. Meanwhile, a second compound type acts as an NCS-1/Ric8a stabiliser, targeting synaptopathies caused by synapse loss, such as AD.

Level of Innovation

NCS-1/Ric8a is the first target known to control the probability of neurotransmitters being released by each synapse, as well as the synapse number. This makes it the first strategy that offers treatment using both of these features at the same time. The first family of compounds is already patented in the US and EU.

Team

Project leader

Alicia Mansilla Aparicio

Project leader

Head of Research in Neuropharmacology

Maria José Casarejos

Medical specialist

Adriano Jiménez Escrig

Contracted scientist

Maria José Sánchez-Barrena

Staff scientist

Ruth Pérez

Head of division

Ana Martínez

Tenured scientist

Carmen Gil

Staff scientist

Nuria Campillo

Head of Innovation Unit

Diego Velasco

Innovation manager

Emma González

MENTOR

Director

Andrés G. Fernández

Ferrer Advanced Biotherapeutics

Partners

Obra social “la Caixa”
Caixa Capital Risc
Validate-18

Scientific Area

Neurosciences

Business area

Therapeutic

Research center

Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal