National Projects

National Projects

  • TEARPLAY – Tear-film Evolution in Antarctic Region: biostrumental, biochemical and behavioural players

Prot. APPLICATION no. PNRA18_00341

Origine dei fondi: Programma Nazionale di Ricerca in Antartide PNRA 2018

Partner: University of Parma

Abstract:On the ocular surface – including tear film, cornea and conjunctiva – significant changes occur when exposed to different physical, chemical and biological conditions or stimuli with aging. Physical stimuli, including wind, humidity, drought, altitude, and UV exposure due to ozone depletion are known to influence the ocular surface. Tears are important for the overall health of the ocular surface, the eye and vision. The blinking process ensures an appropriate protective coating (tear film on the ocular surface). If we don’t blink enough, we can develop exposed areas on the surface of the eye that can affect our vision. Structural and biochemical changes in the tear film strongly influence quality of life [4-7]: the possibility of investigating the physiopathology of the tear film in an extreme environment, such as Antarctica, together with a psychophysical evaluation of human subjects exposed to such an extreme environment would provide a significant opportunity in understanding the mechanisms underlying the pathologies associated with surface damage ocular, after altering the tear film, and develop future personalized therapies with ad hoc tear substitutes. Therefore, the aim of this project is to perform a first detailed evaluation of the evolution of the tear film during the stay in Antarctica, through a complete ophthalmological examination and behavioral evaluation to identify key factors that will be validated on experimental (animal) models in order to provide information to support biochemical countermeasures that will be validated in the second year of the study.

Year: 2020

Total value of the project: €114,650.00 of which €114,650.00 as financial support received from MIUR

Link:

  • Validation of a new multi-targeted monoclonal antibody for the treatment of tumors and retinal diseases

Prot. APPLICATION no. A0375-2020-36583

CUP E85F21001000002

Origin of funds: ERDF European Regional Development Fund – Lazio Regional Operational Program – Programming 2014-2020. Public Notice: “Research Group Projects 2020”

Partner: Università of Rome “Tor Vergata” (Mandatario); Fondation Luigi Maria Monti

Abstract: The general objective of the project consists in the validation of a humanized monoclonal antibody (hD16F7), generated and patented by us, directed against the vascular endothelial growth factor receptor 1 (VEGFR-1), as a therapeutic agent for highly aggressive neoplasms , such as melanoma and glioblastoma, and retinopathies associated with new vessel formation, common causes of blindness. hD16F7 has a multi-targeted mechanism of action different from that of current oncological and ocular antiangiogenic therapies since it specifically inhibits pathological and not physiological angiogenesis, tumor invasiveness and tumor infiltration by immunosuppressive myeloid cells.

Year: 2021

Total value of the project: €149,985.78 of which €149,985.78 as financial support received from the Lazio Region

Link:

http://progettimedicinasistemi.altervista.org/politermab/

Lazio Europe: www.lazioeuropa.it

  • Expansion of the therapeutic applications of Citicoline and development and commercialization pipeline of synthetic derivatives

Prot. APPLICATION no. A0375-2020-36591

CUP E85F21000910002

Origin of funds: ERDF European Regional Development Fund – Lazio Regional Operational Program – Programming 2014-2020. Public Notice: “Research Group Projects 2020”

Partner: University of Rome “Tor Vergata” (Mandatario)

Abstract: This project, making use of the cooperation between biochemists, clinicians and chemists, studies at a molecular and cellular level the effect of Citicoline on cellular proteostasis in order to: (i) expand the therapeutic potential of Citicoline: (ii) design structural modifications of the molecule to enhance its therapeutic efficacy. The results will lead to the characterization of one (or more) second generation derivatives of Citicoline (Citicoline 2.0). In fact, the results obtained in clinical trials on patients suffering from Alzheimer’s disease and Parkinson’s disease have highlighted how Citicoline is able to improve the cognitive and motor performance of the patients themselves, delaying the evolution of the pathology: this has allowed us to identify the molecule as a drug with neuroprotective biological activity. In addition, Citicoline has an exceptional safety profile, useful for maximizing patient compliance, which justifies its wide clinical use, although the mechanism of action is currently unknown.

Year: 2021

Total value of the project: €149,453.15 of which €149,453.15 as financial support received from the Lazio Region

Link:

Origin of funds: AISA NAZIONALE ODV

Abstract: Patients affected by AF may present changes in the retinal structure and morpho-functional alterations of the optic nerve. However, the involvement of the different retinal elements (inner retina and outer retina) of the macular region or of the entire retina and the time of onset are not defined. Therefore, the objective of the study is to evaluate whether there are degenerative morpho-functional alterations of the photoreceptors, bipolar and ganglion cells of the entire retina and/or of the macular region and also of the optic nerve, at an early age of AF disease by comparing the results obtained with those detected both in control subjects and in adult patients with AF.

Year: 2023

Total value of the project: €50,000.00 of which €50,000.00 as financial support received from AISA.

Link:

  • Analysis of functional and structural properties of different proteasome populations: implication in neurodegeneration

Prot. APPLICATION no. 2022R9WCZS

Origin of funds: PNRR – Mission 4 “Education and Research” – Component C2

Investment 1.1 “Fund for the National Research Program and PRIN”: RESEARCH PROJECTS OF RELEVANT NATIONAL INTEREST – Call for tenders 2022

Partner: University of Rome “Tor Vergata” (Mandatario)

Abstract: Dysregulation of the ubiquitin proteasome system (UPS), the main intracellular proteolytic pathway, is associated with the onset and progression of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and glaucoma. A common characteristic of these pathologies is the accumulation of misfolded proteins that aggregate in the affected tissues, interfering with the normal balance of proteostasis and inducing the progressive degeneration and death of neuronal cells.

In this regard, the 26S proteasome is a multi-enzyme system central to the functioning of UPS and composed, in its canonical configuration, of two regulatory particles, known as 20S and 19S. The catalytic activity of 26S as well as that of particles with different compositions (e.g. immunoproteasome) is physiologically responsible for the digestion of damaged or excess proteins and the maintenance of proteostasis. Therefore, pharmacological interventions aimed at modulating the activity of specific proteasome particles and the UPS have emerged as a promising frontier for the development of new therapeutic strategies for neurodegenerative diseases.

The specific objective of the research activity is to define the enzymological properties of proteasome particles with different structural composition compared to substrate proteins involved in neurodegenerative processes in their different conformational states (e.g. soluble or oligomeric monomer).

Achieving this objective is aimed at identifying “drug-like” molecules that are able to modify the intracellular abundance of the different populations of proteasome particles, as well as their catalytic performance towards toxic proteins. To this end, experimental cellular models of neurodegeneration will be set up with particular attention to Alzheimer’s disease and glaucoma (expression of optineurin with E50K mutation in neuronal cells).

The completion of this research project is expected to provide new molecular and biochemical mechanisms underlying proteotoxic damage during neurodegenerative processes and is also expected to provide indications on new possible therapeutic targets.

Year: 2023

Total value of the project: €85,157.00 of which €85,157.00 as financial support received from the MUR.

Link:

  • Assessing central neuromodulation effects on immune-mediated synaptic dysfunction in progressive multiple sclerosis

APPLICATION WFR code PNRR-MCNT2-2023-12377850

Origin of funds: NATIONAL RECOVERY AND RESILIENCE PLAN (PNRR)

MISSION 6 – COMPONENT 2 – INVESTMENT 2.1 VALORIZATION E

ENHANCEMENT OF BIOMEDICAL RESEARCH IN THE SSN

Partner: Neuromed Mediterranean Neurological Institute (Coordinator)

IRCCS-San Raffaele Roma

University of Naples Van Vitelli

Abstract: A profound disruption of the bidirectional cross-talk between the immune and nervous systems is a condition for the pathological development of multiple sclerosis (MS).

In the MS brain, inflammation induces not only demyelination and axonal loss, but also specific abnormalities of synaptic transmission, called inflammatory synaptopathy.

In patients with progressive MS (pwPMS), synaptopathy is characterized by pathological potentiation of glutamate-mediated synaptic upscaling and loss of synaptic long-term potentiation (LTP), both caused by proinflammatory molecules released by microglia, astroglia, and T and B lymphocytes infiltrators.

The Research Project aims to verify whether a neuromodulatory approach, i.e. transcranial static magnetic field stimulation (tSMS), is a valid therapeutic approach for pwPMS, as recently proposed in patients with amyotrophic lateral sclerosis (ALS).

The hypothesis is that a local modulation of neuronal circuits will be able not only to restore aberrant synaptic transmission and plasticity in pwPMS, but also to promote, both at a central and peripheral level, a beneficial and bidirectional brain-immune system communication that will slow down the clinical manifestation of the disease.

Furthermore, the project involves the evaluation of the treatment effect on lymphocyte-mediated synaptotoxicity in chimeric models of MS to provide possible mechanistic effects.

Year: 2024

Total value of the project: €1,000,000.00 of which €1,000,000.00 as financial support received from the European Union NextGenerationEU

Link: