Biologics, Volume 5, Issue 2 (June 2025) – 7 articles

C-terminal-binding proteins (CtBPs) dimerize and function predominantly as transcriptional corepressors by recruiting various chromatin-modifying factors to promoter-bound repressors. Hypotonia, ataxia, developmental delay, and tooth enamel defects syndrome (HADDTS) is a recently discovered neurodevelopmental disorder resulting from a heterozygous missense mutation in CTBP1. It is often associated with the early onset of profound cerebellar atrophy in patients. Allen Institute’s Allen Brain Cell (ABC) atlas of human brain data was used to localize CTBP1 expression in the brain to elucidate the etiology of HADDTS. Based on the ABC atlas, CTBP1 is highly expressed in the upper rhombic lip supercluster, which gives rise to cerebellar cells and provides insights into the cerebellar pathophysiology observed in HADDTS patients. Full article

Sherpabodies are a novel class of antibody-mimetic proteins and represent the third generation of SH3 domain-based targeting scaffolds. Sherpabodies have several advantageous biophysical properties, and molecular libraries based on this scaffold provide a rich and facile source of high-quality binders against diverse target proteins of interest. Recent studies have successfully exploited sherpabodies for developing potent antivirals to block SARS-CoV-2 infection and for the advanced guiding of cancer cell killing by chimeric antigen receptor (CAR)-T cells, but many other applications for sherpabody-mediated targeting in biomedicine and biotechnology can be anticipated. Full article

Background and Objectives: Canakinumab, a human recombinant monoclonal antibody against interleukin-1ß (IL-1ß), is indicated for the treatment of selected autoinflammatory periodic fever syndromes and rheumatic diseases. Data on its use during pregnancy remain limited and all are primarily derived from case reports. Although animal studies indicate no evidence of reproductive toxicity, the risk to the fetus or mother remains unknown. This study aims to provide more findings about this important topic. Methods: A retrospective analysis was conducted on three patients followed and treated in the National Center for Periodic Fever Syndromes. Although due to the small sample size, no general conclusions regarding the safety of canakinumab during pregnancy can be drawn. Results: Three maternal-exposed pregnancies were assessed, with no paternal exposure. Diagnoses included mevalonate kinase deficiency, familiar Mediterranean fever and TNF-receptor-associated periodic syndrome. All mothers were treated with canakinumab, and two of those continued the canakinumab treatment during the whole course of pregnancy. The diseases remained under full control during pregnancy, enabling conception in two cases where attempts prior to treatment were unsuccessful. The therapy led to disease control, a reduction in inflammation and subsequently successful conception. One patient underwent IVF repeatedly. All pregnancies resulted in three healthy infants, with no reported miscarriages during the canakinumab-exposed pregnancies, no complications during pregnancies and no serious infections in the newborns. The children had normal development, without any developmental delays or chronic illnesses. Conclusions: The current data, including our findings, indicate no harmful effects of canakinumab during pregnancy. However, because of the scarcity of data, the use of canakinumab during pregnancy should be carefully managed, and women who want to become pregnant should continue treatment only after a thorough benefit–risk evaluation. Full article

Background: Alopecia areata (AA) is an autoimmune disease affecting 2% of the global population, often causing localized scalp hair loss that can progress to alopecia totalis or universalis. While corticosteroids and JAK inhibitors are effective, their significant side effects highlight the need for safer, more targeted treatments. Recently, biologics have gained attention as potential treatments for AA. Methods: A review of clinical trials, case series, and case reports published on PubMed was conducted to assess the efficacy of cytokine-targeting biologics for the treatment of AA. Data on the mechanism of action, treatment outcomes, and safety were extracted and analyzed. Results: Cytokine-targeting biologics identified included Dupilumab, Secukinumab, Tralokinumab, Etanercept, Ustekinumab, Infliximab, Adalimumab, and Tildrakizumab. Dupilumab and ustekinumab demonstrated strong efficacy, with dupilumab showing significant regrowth in 89% of cases and ustekinumab in all patients. Tralokinumab demonstrated a 33.75% improvement, with no patients achieving SALT₅₀. Limited efficacy was observed with secukinumab, tildrakizumab, and adalimumab, with 71.4%, 77.8%, and 50% of patients, respectively, showing no response. Disease worsening was observed in patients who received etanercept (29%) and infliximab (50%). Conclusions: Further research is necessary to optimize treatment protocols, identify predictive biomarkers, and, crucially, discover novel and more effective cytokine targets to advance biologics as a cornerstone therapy for AA. Full article

Background: Biologics is an exciting and growing area of medicine. Within the larger field of biologics, the use of viral vectors and virus-like particles (VLPs) is increasingly common, making it crucial to develop innovative and practical unit operations for the related purification process. Objective: Some scientists and engineers propose that membrane-based downstream virus purification (MVP) platforms would allow for more scalable and cost-effective production of these critical particles. However, the so-cial, political, and ethical implications of these advancements remain largely unex-plored. This paper aims to explore various pivotal facets of MVP technology govern-ance and regulations within the U.S. context, including (1) government policy ar-rangements related to the implementation of the technologies, (2) stakeholder atti-tudes, policy preferences, and behaviors, and (3) the fundamental factors that shape these attitudes, policy preferences, and behaviors. Methods: In doing so, we analyze publicly available federal and state government documents pertaining to biomanu-facturing, healthcare, and legislative attempts. Additionally, we will perform a stake-holder analysis on relevant industries, healthcare service providers, and recipients. Conclusions: Our goal is to outline the socio-political, ethical, and regulatory factors pertaining to the regulation and governance of these technologies. Full article

Vertebrate cell surfaces exhibit intricate arrangements of glycosaminoglycan polymers, which are primarily linked to lipids and proteins. Numerous soluble secreted proteins are also decorated with either individual sugar molecules or their polymers. The carbohydrate polymers commonly possess terminal nine-carbon sugars, known as sialic acids. Due to their widespread distribution and strategic positioning, sialic acids play a crucial role in mediating and regulating a wide range of physiologic processes and pathologic conditions. Human- or animal-based investigations predominantly concentrate on the effects of sialic acids during infections, inflammations, vascular disorders, or cancers. Further investigations encompass a variety of applications, including cell–cell interactions, signaling, host–pathogen interactions, and other biological functions associated with nutrition, metabolism, or genetic disorders. Nevertheless, future mechanistic investigations are needed to clarify the specific roles of sialic acids in these varied contexts, so that more effective interventions may be developed. Full article

Background/Objectives: Oleuropein (OLP), the key bioactive in olive leaf extracts, has demonstrated various biological benefits. We previously reported on the pro-melanogenic action with increased dendricity of a patented olive leaf extract (Benolea^®) that was standardized to 16–24% OLP. In this study, purified OLP was evaluated to identify if it might be the bioactive responsible for the stimulating effects on melanocytes. Moreover, previous studies on OLP have never reported the effects on melanocyte dendricity or melanin export in the medium. Methods: Herein, the effect of OLP on melanogenesis was first evaluated using the B16F10 cell model and validated using the physiological model of normal human melanocytes from Caucasian (lightly pigmented; LP) and Asian (moderately pigmented; MP) skin. The effects of OLP on melanin export in LP and MP cells were indirectly evaluated by dendricity indices. Results: OLP lowered the intracellular melanin content in B16F10 cells by 26.36%, 24.48%, and 27.71% at 100, 150, and 200 µg/mL (all p < 0.01), respectively, with no effect on the intracellular melanin contents of LP or MP cells. OLP treatment did not influence tyrosinase activity in B16F10 cells or MP cells but significantly enhanced the activity in LP cells. The measurement of extracellular melanin showed significantly higher levels for all three cells, although the levels were considerably higher in MP cells, after the adjustment for OLP autoxidation observed in the cell-free system, which caused melanin-like brown coloration. Furthermore, OLP induced morphological alterations of extended dendrites of B16F10 cells that were retained in LP and MP cells. The quantitation of the dendricity of cells treated with OLP at 200 μg/mL revealed that the total dendrite length was increased by 35.24% (p < 0.05) in LP cells and by 58.45% (p < 0.001) in MP cells without any change in the dendrite number. Conclusions: This is the first study to demonstrate the novel finding that OLP possesses a hitherto unreported unique capacity to stimulate melanocyte dendricity, hence establishing the efficacy for use in increasing human pigmentation. Our findings show significance, with a potential application of the compound OLP for addressing human hypopigmentation disorders in clinical settings or for cosmetic uses related to sunless tanning. Full article