Melatonin MT2-Selective Agonists as a Novel Treatment for Fragile X Syndrome (FXS) and Phelan-McDermid Syndrome (PMS)

Titolo: Melatonin MT2-Selective Agonists as a Novel Treatment for Fragile X Syndrome (FXS) and Phelan-McDermid Syndrome (PMS)

Bando: ERDERA Joint Transnational Call 2025 Full proposal Joint Transnational Call 2025

Durata: 3 anni (dal 01/03/2026 al 28/02/2029)

Responsabile scientifico: Stefano Comai

Budget totale: 228.800 €

Abstract:
Autism spectrum disorder (ASD) affects how people communicate, interact, and behave. Many individuals with ASD also struggle with sleep problems, anxiety, and irritability. Two genetic conditions, Fragile X Syndrome (FXS) and Phelan-McDermid Syndrome (PMS), are closely linked to ASD, but there are no approved treatments for them.
We are developing a new drug called COS01 that targets the melatonin MT2 receptor, which helps regulate sleep and brain function. COS01 has already shown a good safety profile in early tests. Now, we will study how it affects sleep, social behavior, and other ASD-like symptoms in mouse models of FXS and PMS. Our research has four main steps:
1. Studying sleep and behavior – We will examine how FXS and PMS affect sleep and social behavior in mice and see if COS01 helps improve these issues (Canada, Italy).
2. Understanding brain activity – Using advanced tools, we will study how brain circuits are affected in FXS and PMS and whether COS01 can restore normal brain function (Italy).
3. Learning how COS01 works – We will investigate how COS01 activates the MT2 receptor and changes brain cell activity (France). 4. Preparing for human trials – We will create a safe drug formula, test how to measure COS01 in human blood, and submit approval documents for clinical trials (Sweden).
Our goal is to get COS01 ready for human trials within three years, providing the first possible treatment for FXS and PMS. This could greatly improve sleep, anxiety, and overall quality of life for people with these conditions.

  GLIOMERS - Leveraging Polymer Therapeutics as Nanomedicine for Local Glioblastoma Immunotherapy

Titolo: Leveraging Polymer Therapeutics as Nanomedicine for Local Glioblastoma Immunotherapy - GLIOMERS

Bando: 2024 ERC-2024-STG

Durata: 4 anni (dal 01/01/2025 al 31/12/2029 )        

Responsabile scientifico: Alessio  Malfanti

Budget totale: 1.498.175,00€

Abstract:
Research on cancer immunotherapy has not significantly improved survival rates for glioblastoma (GBM). Clinical trials mainly involve systemic drug administration, with limited success due to challenges like the blood-brain barrier, tumor immune microenvironment, and patient variability. An innovative approach involves using biodegradable polymer therapeutics for localized treatment, which may enhance GBM immunotherapy while minimizing side effects. The GLIOMERS project aims to create a brain-penetrating polymeric drug delivery system that combines immunomodulatory effects with chemotherapeutics to boost antitumor immunity. This will be achieved through hybrid nanocarriers using stabilized hyaluronic acid and poly-L-lysine, allowing targeted drug delivery and improved immune response against GBM, advancing nanomedicines for effective treatment.

Link: https://cordis.europa.eu/project/id/101163931

  BIOCOCOMER - Biomolecular condensates and coacervates: from medicine to agriculture

Titolo: Biomolecular condensates and coacervates: from medicine to agriculture - BIOCOCOMER

Bando: 2024 HORIZON-MSCA-2023-SE-01-01 — MSCA Staff Exchanges 2023

Durata: 3 anni (dal 01/01/2025 al 31/12/2028)

Responsabile scientifico: Margherita Morpurgo

Budget totale: 175.000,00 €

Abstract:
BIOCOCOMER aims to achieve three main objectives: Research & Innovation, Training, and International Collaboration. This will involve developing new skills and products through collaboration with partners from Italy, Australia, Portugal, Spain, Cuba, Switzerland, Germany, and South Korea.
The research and innovation objectives include:
1. Engineering and characterizing biomolecular functional condensates and coacervates.
2. Understanding their behavior in cellular environments.
3. Applying these coacervates in gene editing of difficult plants.
The project focuses on designing innovative biomolecular condensates for gene delivery in mammalian cells and plants, using a mix of biomolecules. The goal is to create a library of defined condensates that can recruit RNA and DNA and have applications in medicine and agriculture

Link: https://cordis.europa.eu/project/id/101182806

  RealHOPE

Titolo: Real World Handling of Protein Drugs - Exploration, Evaluation and Education

Acronimo: RealHOPE

Bando: European Commission – Horizon 2020 – SOCIETAL CHALLENGES - Health, demographic change and well-being

Durata: 4 anni

Responsabili scientifiche: Giorgia Miolo, Patrizia Polverino de Laureto

Budget totale: 272.500 €

Abstract:
Innovative protein drugs, genetically engineered versions of human proteins, have the capacity to cure previously incurable diseases. However, they are sensitive due to their complex structure. For instance, they react to shaky transportation or being left beside a sunny window by patients. The EU-funded RealHOPE project will measure real-life events during drug handling by applying smart tag technologies. It will also conduct focus interviews with personnel in hospital pharmacies, clinics and with patients and caregivers to understand current handling practice and what the desired handling instructions and limitations are. These insights will be used to design in use mimicking stability protocols for protein drugs and ultra scaled-down devices for stability assessment.

  BINC

Titolo: Exploring the role of enteric nervous system on myelination during early life: modulation of gut microbiota to prevent neuropsychiatric disorders

Acronimo: BINC (Biostime Institute for Nutrition and Care)

Bando: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722717

Durata: 1 anno

Responsabile scientifico: Prof. Maria Cecilia Giron

Budget totale: 50.000,00 €

Abstract:
The enteric nervous system (ENS) is an extensive neuronal network, embed in the gastrointestinal (GI) tract, that holds sensing machinery for monitoring luminal microbiota-derived perturbations. Since GI microbial colonization and central nervous system (CNS) development occur during a critical window in neonatal life, exposure to dysbiotic events, such as stress or infection in infancy, can disrupt the development of microbiota-gut-brain (MGB) axis, leading to neuropsychiatric disorders (NPDs; e.g., major depressive disorder (MDD), autism spectrum disorders (ASD)). Most neural axons are unmyelinated at birth. During infancy oligodendrocytes ensure rapid myelination, that slowly consolidates spatiotemporally until adulthood to ensure neurotransmission. The prefrontal cortex, undergoing later myelination in newborn, is affected by neonatal intestinal dysbiosis, and highly implicated in NPDs. Intriguingly, the ENS expresses myelin and contains glial cells that share transcriptome features of oligodendrocytes, supporting the hypothesis that ENS is involved in the neuroinflammatory process that disseminates to the CNS. Whether and how NPDs involve the gut is of increasing importance given emerging reports that NPDs are transmitted from the gut to the brain. We found that antibiotic-induced dysbiosis or TLR2/TLR4 deficiency in mice leads to significant morphofunctional ENS changes and altered myelinization, characterized by modified gut motility and susceptibility to neuroinflammation which can be rescued by intraperitoneal administration of GDNF or TLR2 agonists. Following on these findings, we posit that gut dysbiosis causes enteric myelinization changes similar to those seen in NPDs, resulting in ENS neuroinflammation, altered GI motility and impaired cognition, and depends on host-microbiota interactions. The proposed multidisciplinary study will integrate the science of neurogastroenterology with neuropsychopharmacology. This hypothesis will be tested with three aims performed in the cuprizone mouse model. First, we will evaluate whether cuprizone administration causes enteric disrupted myelinization, neuroimmune changes and neuronal loss. Second, we will assess whether disruption in gut motility precedes impaired cognition. Finally, using experimental manipulation of the microbiota, we will explore the role of host-microbiota interactions in NPDs-associated GI disease and their relationship to cognition. Specifically, we will examine whether and how NPDs progression is affected by antibiotic-mediated dysbiosis, or TLR2 stimulation. Successful completion of the proposed studies will identify critical pathophysiological pathways that affect the gut and precede the onset of NPDs. The results will inform novel prevention and intervention strategies for NPDs and cognitive dysfunction during infancy.