Il Dipartimento è risultato vincitore di due progetti PRIN
BANDO PRIN 2022 – PI per il Dipartimento Prof. Antonio Minni
Infections caused by SARS-CoV-2, defined as coronavirus disease-19 (COVID-19), cause sickness varying from the common cold to more severe illnesses such as severe acute respiratory syndrome, sudden stroke, neurological complications (Neuro-COVID), multiple organ failure, and mortality in some patients. In addition, it is now becoming increasingly evident that SARS-CoV-2 is able to cause a complex chronic clinical manifestation of signs and symptoms in the form of long-COVID syndrome without a complete recovery from the COVID-19. Significant COVID-19 patients exhibit neurological deficits, such as olfactory and cognitive impairment, altered memory/thinking, delayed latent periods in recalling events of the recent past, anxiety, depression, described as mental fog, namely NeuroCOVID. The most pressing challenge in the post-COVID condition is to understand the mechanisms underlying multiorgan pathology and in particular the pathogenesis of neurological signs and symptoms of NEUROCOVID.
To address the neurobiological effects in Post-COVID-19 (PCS) conditions we will extend our preliminary study on a recruited PCS patient cohort (Ethical Committee of Sapienza University of Rome, Hospital Umberto I, approval n. 6536). By nasal biopsies of a limited cohort of second-wave PCS patients, we observed an alteration of mitochondrial functions and structure and an increase of specific neuronal markers by biochemical and ultrastructural analysis. Second, we collected data by a questionnaire developed as a web tool structured in two parts. 1) Demographics and Post-Covid-19 clinical related history 2) Memory impairment assessment questionnaire (MAC-Q), Stai-Y2, and QD (CBA 2.0) for mental health assessment. We validated 141 questionnaires (part 1); 74 questionnaires (part 2) and only 49 as integrated (part 1+2). These QS were collected (Dec. 2021) from volunteers after pandemic waves (2020 and 2021), which developed a PCS condition.
They belong to a wide large collection of over 2000 interviewed subjects, as described in the web page project (https://www.sindromepostcovid19.it/) We found a high prevalence of Fatigue/asthenia, shortness of breath, sleep disturbances, reduced concentration, alteration of smell, and memory loss. In addition, from part 2 analysis, a high prevalence of psychiatric diagnoses was observed, primarily 71.6% were affected by daily memory disturbances (cut-off ≥ 25); 83.8% anxiety (cut-off > 41), and 36,48% (27/74) depression. We recorded a very significant correlation between the MAC-Q scales, STAY, and QD.
With the aim of exploring the neurobiological and neuropsychological correlates in the PCS conditions, and BIOMARKERS in the particular relationship between olfactory dysfunction and deterioration cognitive as common features of the NEUROCOVID, this project is based on integrated models of biological, clinical, engineering, and computer science will analyze NEUROCOVID by triple way: SOLID, LIQUID AND GAS BIOPSIES (NEUROVOLATILOME).
BANDO PRIN 2015 – PI Prof. Alessandro Lambiase
The objective of the project is to evaluate the clinical use of neurotrophin profiling and genotyping as novel biomarkers of disease development, progression and response to treatment, in age-related macular degeneration (AMD) and glaucoma (GL), and to develop novel neurotrophin-based therapies to improve diseases’ outcome. A multidisciplinary approach involving a close interaction between bioengineers, pharmacologists, chemists, neurobiologists and ophthalmologists is proposed to achieve these objectives.
Currently, AMD and GL represent the first cause of irreversible blindness worldwide, being orphan of treatments able to modify visual outcome. Neuroprotective and neuroregenerative therapies that could rescue the impaired visual function, are therefore one of the primary challenges in the management of these diseases. Nerve Growth Factor (NGF) is the most promising neurotrophin to be used as a biomarker and/or therapeutic agent in ophthalmology. Experimental and clinical evidences show that NGF might prevent apoptosis and stimulate neurorepair during different retinal injuries, including glaucoma.
The project will comprise clinical and preclinical studies. The multicenter clinical trial on AMD and GL patients is aimed to identify clinical biomarkers predictive of disease outcomes, and a target population that could benefit from neurotrophin treatment, by correlating clinical parameters to neurotrophin profiling and genotyping. All patients will be followed for 2,5 years by complete ophthalmic examination, including morphological and functional evaluation of the visual function.
Peripheral blood, tears and conjunctival epithelium will be collected during the follow-up and used to measure the levels of neurotrophins, neurotrophin precursors and receptors, as well as to direct the sequencing of NGF and NGF receptor genes and to evaluate gene methylation status.
The preclinical studies will be carried out to investigate the potential use of a neurotrophin-based therapy. To establish the best dose regimen and route of administration, pharmacokinetics and pharmacodynamics of recombinant human NGF (rhNGF) administered as eye drops or intravitreal injection will be investigated. Furthermore, the project will test a recently developed rhNGF slow-release device for intravitreal or subconjunctival implant and the use of small molecules with NGF mimetic activity.
The safety and efficacy of the selected neurotrophin treatments – in terms of neuroprotective and regenerative actions – will be subsequently evaluated in animal models of AMD or GL by analysing the survival, differentiation and distribution of retinal pigment epithelial cells, retinal ganglion cell (RGC) and retinal precursor cells, as well as the expression of factors favouring RGC growth, and factors inhibiting neural regeneration.
The integrated findings from clinical and preclinical studies will allow the design and implementation of a NGF-based treatment for GL and AMD patients.