recombinant surfactant protein D (rhSP-D) / Trimunocor - LARVOL DELTA

A phase 1b randomized, multicenter, dose determination trial of zelpultide alfa (recombinant human surfactant protein D) in preterm neonates at high risk of developing bronchopulmonary dysplasia. (PubMed, Front Pediatr) - P1 | "Bronchopulmonary dysplasia (BPD) ranks among the most severe long-term complications of prematurity. The incidence of BPD was 32.1% vs. 66.7%, the incidence of BPD or death was 54% and 67%, and time on mechanical ventilation was 17.7 vs. 25.8 days in the zelpultide alfa group compared to the air-sham group, respectively. This study endorses the safety and tolerability of zelpultide alfa up to 6 mg/kg (≤7 days) and reinforces the need for further clinical development of zelpultide alfa as a therapy for preventing BPD.Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04662151?cond=BPD&term=At-100&rank=1, identifier NCT04662151."

Clinical • Journal • P1 data • Bronchopulmonary Dysplasia • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

RESPONSE: Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: University College, London | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

In Silico Binding of Computationally Folded Structures of Human Surfactant Protein D (hSP-D) to SARS-CoV-2 Spike Wild Type and ACE2 Show Low Likelihood of SP-D's Role in Blocking SARS-CoV-2 ACE2 Binding (ATS 2025) - "This abstract is funded by: Chester Robbins Endowment (AH) Rationale While human surfactant protein D (hSP-D) has been of immunological interest for its antiviral capabilities over at least the past two decades, there do not currently exist experimentally derived structural images that include all of hSP-D's amino acids of importance, especially the N-Acetylglucosamine (NAG) binding site at Asparagine amino acid site number 90 (ASN90). Clearly, computational folding methods can lead to dramatically different protein structure models than their X-ray or other experimentally-derived counterparts. This would make sense, considering that all three methods used here (AlphaFold, I-TASSER, ESMFold) use data from other, similar structures to be able to derive high confidence structures, but do not necessarily detail molecular conformations or even stoichiometry for effective protein structure determinations."

Surfactant • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro. (PubMed, Biochem J) - "In this work, we describe a method to produce recombinant SPD-modified tau where SPD modifications are mainly localized to Q residues within the N-terminus...On the other hand, SPD modification promotes the formation of pathogenic conformations (e.g. oligomerization and misfolding) by tau with or without inducing tau polymerization. Taken together, these data suggest that SPD polyamination of tau enhances its ability to polymerize microtubules and favors the adoption of pathogenic tau conformations but not filamentous aggregates in vitro."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Development of a prediction model for progression of rheumatoid arthritis-associated interstitial lung disease using serologic and clinical factors: The prospective KORAIL cohort. (PubMed, Semin Arthritis Rheum) - "In this prospective cohort, UIP pattern, ILD extent, lower DLCO, RA disease activity, anti-CCP levels, and pulmonary damage biomarkers were associated with RA-ILD progression. We developed prediction models that may be clinically useful to risk stratify once externally validated."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology

Serum Biomarkers of Pulmonary Damage and Risk for Progression of Rheumatoid Arthritis-Associated Interstitial Lung Disease. (PubMed, J Rheumatol) - "In this first prospective study to apply PPF criteria to RA-ILD, 34.6% progressed over 3 years. Higher baseline KL-6 and hSP-D were associated with progression. In follow-up, greater change in KL-6 was associated with progression. Serial measurement of pulmonary damage biomarkers may predict RA-ILD progression and may be helpful in monitoring patients and treatment decisions."

Biomarker • Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • MMP7

RESPONSE: Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University College, London | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Jul 2024 ➔ Nov 2025

Enrollment open • Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

Pulmonary Damage Biomarkers and Progression of Rheumatoid Arthritis-associated Interstitial Lung Disease in a Prospective Longitudinal Cohort (ACR Convergence 2024) - "The aim of this study was to investigate the associations of baseline and change in pulmonary damage biomarkers (serum Kreb von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloprotein 7 [MMP7]) with ILD progression among patients with RA-ILD. We investigated RA-ILD progression in the Korean RA-ILD (KORAIL) cohort, a prospective, longitudinal observational study that enrolled patients with RA based on 1987 ACR or 2010 ACR/EULAR criteria and ILD on chest computed tomography (CT) scans from January 2015 to July 2018, followed for 3 years... In this first longitudinal cohort study to apply recently developed criteria of PPF to RA-ILD, 35% progressed during 3 years of follow-up. Higher baseline levels of KL-6 and hSP-D were associated with RA-ILD progression. In follow-up, greater changes in KL-6 and MMP7 were associated with progression."

Biomarker • Clinical • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • MMP7

Serologic and Clinical Predictors of Progressive Pulmonary Fibrosis in Rheumatoid Arthritis-associated Interstitial Lung Disease Progression: A Prospective Longitudinal Cohort (ACR Convergence 2024) - "In addition, anti-cyclic citrullinated peptide (anti-CCP, HR 1.30 per SD increase, 95%CI 1.00-1.69), Krebs von den Lungen-6 (KL-6, HRs 1.39 per SD increase, 95%CI 1.06-1.82), human surfactant protein D (hSP-D, HR 1.43 per SD increase, 95%CI 1.10-1.88), and matrix metalloprotein 7 (MMP7, HR 1.44 per SD increase, 95% CI 1.10-1.89) levels were associated with progression... In this prospective cohort that applied the recent PPF definition to RA-ILD, we identified traditional predictors of progression that included UIP pattern, ILD extent, lower DLCO, and the pulmonary damage biomarkers KL-6, hSP-D, and MMP7. In addition, we identified RA disease activity and anti-CCP antibody levels as novel RA-related predictors of progression. The model combining these factors had high predictive performance, so may be clinically useful to risk stratify for treatment consideration once externally validated."

Clinical • Fibrosis • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • MMP7

Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit. (PubMed, BMJ Open) - P1 | "ISRCTN17083028, NCT05898633. RESPONSE Protocol V.4.0 24th July 2024."

Clinical protocol • Journal • P1 data • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Cardiovascular • Critical care • Inflammation • Inflammatory Arthritis • Pulmonary Disease • Respiratory Diseases

SERUM BIOMARKERS OF PULMONARY DAMAGE AND RISK FOR PROGRESSION OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (EULAR 2024) - "Objectives: To investigate the associations of baseline and change of pulmonary damage biomarkers (serum Kreb von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloprotein 7 [MMP7]) with ILD progression among patients with RA-ILD... Higher levels of serum KL-6 and hSP-D were each associated with increased risk of RA-ILD progression. Higher KL-6 levels were most consistently associated with progression. At follow-up, increasing serum KL-6 and MMP7 level was also associated with increased risk of progression."

Biomarker • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • MMP7

Expression and basic biochemical characteristics of recombinant surfactant protein D of bottlenose dolphin (Tursiops truncatus). (PubMed, Protein Expr Purif) - "In this short report, recombinant SP-D of bottlenose dolphin (dSP-D) was synthesized in mammalian cells, and its properties were analyzed in vitro...Enzyme-linked immunosorbent assay-like methods revealed that recombinant dSP-D bonded to gram-positive and gram-negative bacterial walls. Our findings suggest the clinical usefulness of dSP-D for cetacean pneumonia."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Adjuvant Therapy With a Recombinant Fragment of Human Surfactant Protein D Increases Airspace, Improves Lung Compliance, and Reduces Levels of Pro-inflammatory Cytokines in Ventilated Preterm Lambs (ATS 2024) - "IT rfhSP-D in preterm lambs did not adversely affect the action of standard surfactant therapy but is likely to complement it as seen by several improved lung parameters in the rfhSP-D treated group. rfhSP-D has anti-inflammatory activity as demonstrated by increased alveolar space and lower expression of pro-inflammatory cytokines such as IL-6 and IL-1β in the treated group. These results support the use of this rfhSP-D as a therapy in preterm infants at risk of BPD."

Clinical • Compliance • Prematurity • Surfactant • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Inflammation • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL1B • IL6 • TNFA

The Anti-inflammatory Interaction of Human Surfactant Protein D (SP-D) With Monocyte-derived Dendritic Cells in Allergic Asthma (ATS 2024) - "moDC were shown to have matured after allergen exposure, with indicative NFκB activation and surface marker changes. The binding of hSP-D and rfhSP-D to the allergen follows the expected pattern, indicating their use of the carbohydrate recognition domain. hSP-D is also able to interact with moDC, exerting an anti-inflammatory effect on them."

IO biomarker • Surfactant • Allergy • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CD40 • CD86 • IL4

RESPONSE: Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University College, London | Initiation date: Jul 2023 ➔ Dec 2023

Trial initiation date • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases

The hybrid molecule CL-SP-D has the potential to regulate xenogeneic rejection by human neutrophils (IPITA-IXA-CTRMS 2023) - " The cDNA for the carbohydrate recognition domain (CRD) of human surfactant protein D (SP-D) was swiched to that of a membrane-type protein, collectin placenta 1 (CL-P1)... These results indicate that CL-SP-D is very effective on neutrophils in xenogeneic rejection. Moreover, CL-SP-D was significantly more effective than CD47 as a molecule to inhibit the neutrophil-mediated xenogeneic rejection."

CD47 • IL10 • SIRPA

Circulating Surfactant Protein D: A Biomarker for Acute Lung Injury? (PubMed, Biomedicines) - "Recent studies have reported that SP-D has a superior discriminatory ability compared to other lung epithelial proteins for the diagnosis of ARDS, which could reflect the severity of lung injury. Furthermore, we shed light on recombinant SP-D treatment and its benefits as a potential drug for ALI, and we encourage further studies to translate SP-D into clinical use for diagnosis and treatment."

Biomarker • Journal • Review • Acute Lung Injury • Acute Respiratory Distress Syndrome • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Analysis of the mechanisms regulating soluble PD-1 production and function in human NK cells. (PubMed, Front Immunol) - "We produced the recombinant sPD-1 protein and demonstrated that it binds PD-L1 and that its presence results in increased NK cell cytotoxicity...Secreted endogenous sPD-1, retained its biological function and could modulate NK cell effector function. Overall, these data reveal a pivotal role of sPD-1 in regulating NK-mediated innate immune responses."

IO biomarker • Journal • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • PD-1

RESPONSE: Recombinant Surfactant Protein D (rfhSP-D) to Prevent Neonatal Chronic Lung Disease (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University College, London

New P1 trial • Acute Respiratory Distress Syndrome • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases • ELANE • IL6

Elevated Sputum Group 2 Innate Lymphoid Cells Indicates Clinical Severity of Chronic Obstructive Pulmonary Disease and Involves IL-17A Plasticity (ATS 2023) - "In ILC2 cell cultures in vitro, recombinant SP-D dose-dependently suppressed RORγt and IL-17A release. The presence of sputum ILC2s correlates with the clinical severity of COPD. This shows a novel pathway of IL-17A plasticity in lung ILC2s that is prevented by the pleiotropic immunomodulatory protein SP-D."

Clinical • Chronic Obstructive Pulmonary Disease • Immune Modulation • Immunology • Pulmonary Disease • Respiratory Diseases • GATA3 • IL13 • IL17A • IL5