Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial.

Background: Dry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis.

The History of Nerve Growth Factor: From Molecule to Drug.

Nerve growth factor (NGF), the first neurotrophin to be discovered, has a long and eventful research journey with a series of turning points, setbacks, and achievements. Since the groundbreaking investigations led by Nobel Prize winner Rita Levi-Montalcini, advancements in the comprehension of NGF's functions have revolutionized the field of neuroscience, offering new insights and opportunities for therapeutic innovation. However, the clinical application of NGF has historically been hindered by challenges in determining appropriate dosing, administration strategies, and complications related to the production process.

Phase IV Multicenter, Prospective, Open-Label Clinical Trial of Cenegermin (rhNGF) for Stage 1 Neurotrophic Keratopathy (DEFENDO).

Introduction: Cenegermin is approved for treatment of neurotrophic keratopathy (NK) and has been studied in patients with stage 2 or 3 NK. This study evaluated the efficacy and safety of cenegermin in adults with stage 1 NK.

Methods: This was a phase IV, multicenter, prospective, open-label, uncontrolled trial.

Efficacy and Safety of Reparixin in Patients with Severe COVID-19 Pneumonia: A Phase 3, Randomized, Double-Blind Placebo-Controlled Study.

Introduction: Polymorphonuclear cell influx into the interstitial and bronchoalveolar spaces is a cardinal feature of severe coronavirus disease 2019 (COVID-19), principally mediated by interleukin-8 (IL-8). We sought to determine whether reparixin, a novel IL-8 pathway inhibitor, could reduce disease progression in patients hospitalized with severe COVID-19 pneumonia.

Methods: In this Phase 3, randomized, double-blind, placebo-controlled, multicenter study, hospitalized adult patients with severe COVID-19 pneumonia were randomized 2:1 to receive oral reparixin 1200 mg three times daily or placebo for up to 21 days or until hospital discharge.

Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest.

Background: Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA.

Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID-19) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin-8 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease.

A Multicenter Phase 2 Randomized Controlled Study on the Efficacy and Safety of Reparixin in the Treatment of Hospitalized Patients with COVID-19 Pneumonia.

Introduction: Acute lung injury and acute respiratory distress syndrome are common complications in patients with coronavirus disease 2019 (COVID-19). Poor outcomes in patients with COVID-19 are associated with cytokine release syndrome. Binding of interleukin-8 (CXCL8/IL-8) to its chemokine receptors, CXCR1/2, may mediate this inflammatory process.

Ladarixin, an inhibitor of the interleukin-8 receptors CXCR1 and CXCR2, in new-onset type 1 diabetes: A multicentre, randomized, double-blind, placebo-controlled trial.

Aim: To evaluate the ability of ladarixin (LDX, 400 mg twice-daily for three cycles of 14 days on/14 days off), an inhibitor of the CXCR1/2 chemokine receptors, to maintain C-peptide production in adult patients with newly diagnosed type 1 diabetes.

Materials And Methods: A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 males and 31 females (aged 18-46 years) within 100 days of the first insulin administration. The primary endpoint was the area under the curve (AUC) for C-peptide in response to a 2-hour mixed meal tolerance test (AUC ) at week 13 ± 1.

A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19.

Background: Current available therapeutic options for Coronavirus Disease-2019 (COVID-19) are primarily focused on treating hospitalized patients, and there is a lack of oral therapeutic options to treat mild to moderate outpatient COVID-19 and prevent clinical progression. Raloxifene was found as a promising molecule to treat COVID-19 due to its activity to modulate the replication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and act as an immunomodulator to decrease proinflammatory cytokines.

Methods: This was a phase 2 multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of raloxifene in adult patients with mild to moderate COVID-19 between October 2020 to June 2021 in five centers located in Italy.

Intravitreal Administration of rhNGF Enhances Regenerative Processes in a Zebrafish Model of Retinal Degeneration.

Nerve growth factor (NGF) is the best characterized neurotrophin, and it is known to play an important role in ocular homeostasis. Here, we demonstrated the expression of NGF receptors in adult zebrafish retina and optimized a light-induced retina degeneration (LID) zebrafish model that mimics human cone-rod disorders, demonstrating that intravitreal (IV) administration of rhNGF can boost zebrafish retinal regeneration in this model. Adult zebrafish retinae exposed to 60 h of light irradiation (60 h LID) displayed evident reduction of outer nuclear layer (ONL) thickness and cell number with presence of apoptotic cells.

The Role of Interleukin-8 in Lung Inflammation and Injury: Implications for the Management of COVID-19 and Hyperinflammatory Acute Respiratory Distress Syndrome.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) has resulted in the global spread of Coronavirus Disease 2019 (COVID-19) and an increase in complications including Acute Respiratory Distress Syndrome (ARDS). Due to the lack of therapeutic options for Acute Respiratory Distress Syndrome, recent attention has focused on differentiating hyper- and hypo-inflammatory phenotypes of ARDS to help define effective therapeutic strategies. Interleukin 8 (IL-8) is a pro-inflammatory cytokine that has a role in neutrophil activation and has been identified within the pathogenesis and progression of this disease.

Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

Comparison of Efficacy of Ketoprofen and Ibuprofen in Treating Pain in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Introduction: Patients with rheumatoid arthritis (RA) or other rheumatic diseases say that pain and stiffness are symptoms affecting their quality of life. Ketoprofen and ibuprofen are the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs) to reduce inflammation and manage mild-to-moderate pain. The aim of this new systematic review of the literature and meta-analysis of randomized controlled trials (RCTs) was to compare the clinical efficacy of ketoprofen and ibuprofen in patients with RA.

Taurine and oxidative stress in retinal health and disease.

Retinal disorders are leading causes of blindness and are due to an imbalance between reactive oxygen species and antioxidant scavenger (in favor of pro-oxidant species) or a disruption of redox signaling and control. Indeed, it is well known that oxidative stress is one of the leading causes of retinal degenerative diseases. Different approaches using nutraceuticals resulted in protective effects in these disorders.

Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial.

Purpose: To evaluate the efficacy and safety of topical cenegermin (recombinant human nerve growth factor) in patients with neurotrophic keratopathy.

Design: Multicenter, randomized, double-masked, vehicle-controlled trial.

Participants: Patients with neurotrophic persistent epithelial defect with or without stromal thinning.

Effect of recombinant human nerve growth factor eye drops in patients with dry eye: a phase IIa, open label, multiple-dose study.

Background: Dry eye disease (DED) affects more than 14% of the elderly population causing decrease of quality of life, high costs and vision impairment. Current treatments for DED aim at lubricating and controlling inflammation of the ocular surface. Development of novel therapies targeting different pathogenic mechanisms is sought-after.

Allergy screening in a schoolchildren-based population.

Background: Schoolchildren screening for allergic diseases may improve early identification and management of atopic children. The aim of this study was to perform a schoolchildren screening program for identification of children with allergic diseases.

Methods: All parents of children attending to 13 primary schools in the city of Rome were requested to fill in a demographic data form and the ChAt questionnaire.

Inflammatory Stress Causes N-Glycan Processing Deficiency in Ocular Autoimmune Disease.

High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells.

Recombinant Human Nerve Growth Factor Treatment Promotes Photoreceptor Survival in the Retinas of Rats with Retinitis Pigmentosa.

Purpose: Increasing evidence suggests that nerve growth factor (NGF) exerts protective effects against retinal degeneration in animal models of retinitis pigmentosa (RP). This study aims at investigating the effects of intravitreal injection of recombinant human NGF (rhNGF) on retinal photoreceptors apoptosis in an animal model of RP, the Royal College of Surgeons (RCS) rats.

Methods: Thirty-six RCS rats were treated with intravitreal injection of rhNGF or murine NGF (mNGF) or vehicle at 20 postnatal days (pd) and sacrificed at 40 pd.

Retinal pigment epithelium-photoreceptor layer alterations in a patient with Sturge-Weber syndrome with diffuse choroidal hemangioma.

Purpose: To describe an 8-year-old girl with diagnosis of Sturge-Weber syndrome (SWS) presenting with glaucoma, abnormal iris vessels, diffuse choroidal hemangioma, and small white dot-shaped "microdrusen-like" alterations of the retina in the right eye.

Patient And Methods: Complete ophthalmological examination was performed with slit-lamp anterior segment assessment and fundus ophthalmoscopy. Near infrared reflectance (NIR) and enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD-OCT) were carried out.

A Two-Week, Randomized, Double-masked Study to Evaluate Safety and Efficacy of Lubricin (150 μg/mL) Eye Drops Versus Sodium Hyaluronate (HA) 0.18% Eye Drops (Vismed®) in Patients with Moderate Dry Eye Disease.

Purpose: The objective of this clinical trial (NCT02507934) was to assess the efficacy and safety of recombinant human lubricin as compared to a 0.18% sodium hyaluronate (HA) eye drop in subjects with moderate dry eye disease (DED).

Methods: DEWS Grade 2-3 subjects were randomized to use lubricin (N=19, 51.