Phase 3 Trial of Concizumab in Hemophilia with Inhibitors.

BACKGROUND: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody designed to achieve hemostasis in all hemophilia types, with subcutaneous administration. A previous trial of concizumab (explorer4) established proof of concept in patients with hemophilia A or B with inhibitors. METHODS: We conducted the explorer7 trial to assess the safety and efficacy of concizumab in patients with hemophilia A or B with inhibitors. Patients were randomly assigned in a 1:2 ratio to receive no prophylaxis for at least 24 weeks (group 1) or concizumab prophylaxis for at least 32 weeks (group 2) or were nonrandomly assigned to receive concizumab prophylaxis for at least 24 weeks (groups 3 and 4). After a treatment pause due to nonfatal thromboembolic events in three patients receiving concizumab, including one from the explorer7 trial, concizumab therapy was restarted with a loading dose of 1.0 mg per kilogram of body weight, followed by 0.2 mg per kilogram daily (potentially adjusted on the basis of concizumab plasma concentration as measured at week 4). The primary end-point analysis compared treated spontaneous and traumatic bleeding episodes in group 1 and group 2. Safety, patient-reported outcomes, and pharmacokinetics and pharmacodynamics were also assessed. RESULTS: Of 133 enrolled patients, 19 were randomly assigned to group 1 and 33 to group 2; the remaining 81 were assigned to groups 3 and 4. The estimated mean annualized bleeding rate in group 1 was 11.8 episodes (95% confidence interval [CI], 7.0 to 19.9), as compared with 1.7 episodes (95% CI, 1.0 to 2.9) in group 2 (rate ratio, 0.14 [95% CI, 0.07 to 0.29]; P<0.001). The overall median annualized bleeding rate for patients receiving concizumab (groups 2, 3, and 4) was 0 episodes. No thromboembolic events were reported after concizumab therapy was restarted. The plasma concentrations of concizumab remained stable over time. CONCLUSIONS: Among patients with hemophilia A or B with inhibitors, the annualized bleeding rate was lower with concizumab prophylaxis than with no prophylaxis. (Funded by Novo Nordisk; explorer7 ClinicalTrials.gov number, NCT04083781.).

Pathogen-mediated natural and manipulated population collapse in an invasive social insect.

SignificanceInvasive social insects are among the most damaging of invasive organisms and have proved universally intractable to biological control. Despite this, populations of some invasive social insects collapse from unknown causes. We report long-term studies demonstrating that infection by a microsporidian pathogen causes populations of a globally significant invasive ant to collapse to local extinction, providing a mechanistic understanding of a pervasive phenomenon in biological invasions: the collapse of established populations from endogenous factors. We apply this knowledge and successfully eliminate two large, introduced populations of these ants. More broadly, microsporidian pathogens should be evaluated for control of other supercolonial invasive social insects. Diagnosing the cause of unanticipated population collapse in invasive organisms can lead to applied solutions.

Tagged actin mRNA dysregulation in IGF2BP1[Formula: see text] mice.

Gene expression is tightly regulated by RNA-binding proteins (RBPs) to facilitate cell survival, differentiation, and migration. Previous reports have shown the importance of the Insulin-like Growth Factor II mRNA-Binding Protein (IGF2BP1/IMP1/ZBP1) in regulating RNA fate, including localization, transport, and translation. Here, we generated and characterized a knockout mouse to study RBP regulation. We report that IGF2BP1 is essential for proper brain development and neonatal survival. Specifically, these mice display disorganization in the developing neocortex, and further investigation revealed a loss of cortical marginal cell density at E17.5. We also investigated migratory cell populations in the IGF2BP1[Formula: see text] mice, using BrdU labeling, and detected fewer mitotically active cells in the cortical plate. Since RNA localization is important for cellular migration and directionality, we investigated the regulation of ß-actin messenger RNA (mRNA), a well-characterized target with established roles in cell motility and development. To aid in our understanding of RBP and target mRNA regulation, we generated mice with endogenously labeled ß-actin mRNA (IGF2BP1[Formula: see text]; ß-actin-MS2[Formula: see text]). Using endogenously labeled ß-actin transcripts, we report IGF2BP1[Formula: see text] neurons have increased transcription rates and total ß-actin protein content. In addition, we found decreased transport and anchoring in knockout neurons. Overall, we present an important model for understanding RBP regulation of target mRNA.

Study Design and Protocol of the Multisite Pregnancy 24/7 Cohort Study.

Hypertensive disorders of pregnancy and other adverse pregnancy outcomes (APOs) are associated with an increased risk of future maternal cardiovascular disease. Physical activity during pregnancy reduces the risk of these APOs, yet few meet physical activity guidelines during pregnancy. Little is known about the role of sedentary behavior or sleep in APOs, a critical gap in knowledge given these behaviors comprise the majority of a 24-hour day. To address this knowledge gap, the Pregnancy 24/7 cohort study (2020-2025) uses 2 devices for 24-hour activity assessment in each trimester of pregnancy to examine associations of sedentary behavior, sleep, and the 24-hour activity cycle (composition of sedentary behavior, physical activity, and sleep) with hypertensive disorders and other APOs. Participants (n = 500) are recruited from the University of Iowa, University of Pittsburgh, and West Virginia University in early pregnancy and followed through delivery. The activPAL3 micro and Actiwatch Spectrum Plus are worn in each trimester for 7 days of 24-hour wear to assess the 24-hour activity cycle. APOs are abstracted from medical charts. This study will provide critical data to fuel future research examining how modifying the 24-hour activity cycle in pregnancy can improve maternal health.

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila.

Transportin-2 (TNPO2) mediates multiple pathways including non-classical nucleocytoplasmic shuttling of >60 cargoes, such as developmental and neuronal proteins. We identified 15 individuals carrying de novo coding variants in TNPO2 who presented with global developmental delay (GDD), dysmorphic features, ophthalmologic abnormalities, and neurological features. To assess the nature of these variants, functional studies were performed in Drosophila. We found that fly dTnpo (orthologous to TNPO2) is expressed in a subset of neurons. dTnpo is critical for neuronal maintenance and function as downregulating dTnpo in mature neurons using RNAi disrupts neuronal activity and survival. Altering the activity and expression of dTnpo using mutant alleles or RNAi causes developmental defects, including eye and wing deformities and lethality. These effects are dosage dependent as more severe phenotypes are associated with stronger dTnpo loss. Interestingly, similar phenotypes are observed with dTnpo upregulation and ectopic expression of TNPO2, showing that loss and gain of Transportin activity causes developmental defects. Further, proband-associated variants can cause more or less severe developmental abnormalities compared to wild-type TNPO2 when ectopically expressed. The impact of the variants tested seems to correlate with their position within the protein. Specifically, those that fall within the RAN binding domain cause more severe toxicity and those in the acidic loop are less toxic. Variants within the cargo binding domain show tissue-dependent effects. In summary, dTnpo is an essential gene in flies during development and in neurons. Further, proband-associated de novo variants within TNPO2 disrupt the function of the encoded protein. Hence, TNPO2 variants are causative for neurodevelopmental abnormalities.

Building Power on "Mass&Cass": A Community-Centered Approach to Addressing Health Resource Gaps for Persons Experiencing Homelessness in Boston, MA, 2021.

In November 2021, two grassroots organizations in Boston, Massachusetts-a housing and health justice organization and a student-led nonprofit-established an initiative to provide persons experiencing homelessness (PEH) near the Massachusetts Avenue and Melnea Cass Boulevard ("Mass&Cass") intersection in Boston with access to free COVID-19 education and other wrap-around services. They partnered with hospitals, public health organizations, and advocacy groups to make this happen. This community-driven initiative serves as a model for how to enact a sustainable pipeline for PEH to receive health resources and information, with the voices of those directly impacted at the center. (Am J Public Health. 2024;114(9):870-873. https://doi.org/10.2105/AJPH.2024.307713).

Disease and treatment burden of patients with haemophilia entering the explorer6 non-interventional study.

OBJECTIVES: We aimed to characterise baseline disease and treatment burden in a large population with haemophilia A/B, both with (HAwI/HBwI) and without (HA/HB) inhibitors. METHODS: The prospective, non-interventional explorer6 study included patients ≥12 years old with severe HA, severe/moderate HB or HAwI/HBwI of any severity, treated according to local standard of care (excluding previous/current exposure to concizumab or emicizumab). Baseline characteristics and historical clinical data were collected and patient-reported outcomes, including treatment burden, were assessed. RESULTS: The explorer6 study enrolled 231 patients with haemophilia (84 HAwI/HBwI) from 33 countries. At baseline, patients with HA/HB treated with prophylaxis had the lowest median annualised bleeding rates (ABRs; 2.0), irrespective of haemophilia type; of these patients, 27.5% (HA) and 31.4% (HB) had target joints. Patients with HAwI/HBwI treated episodically reported the highest treatment burden. Of these patients, 28.5% (HAwI) and 25.1% (HBwI) performed sports activities in the month before screening. CONCLUSION: Despite receiving routine clinical care, historical and baseline information from patients enrolled in explorer6 showed that patients with HA/HB treated episodically and patients with HAwI/HBwI had higher ABRs, higher treatment burden and participated in sports less than those with HA/HB treated with prophylaxis. Emerging treatments could be beneficial in addressing these unmet medical needs.

Size Distributions of Microplastics in the St Louis Estuary and Western Lake Superior.

Identifying the sources and fate of microplastics in natural systems has garnered a great deal of attention because of their implications for ecosystem health. This work characterizes the size fraction, morphology, color, and polymer composition of microplastics in western Lake Superior and its adjacent harbor sampled in August and September 2021. The results reveal that the overall microplastic counts are similar, with the harbor stations ranging from 0.62 to 3.32 microplastics per liter and the lake stations ranged from 0.83 to 1.4 microplastics per liter. However, meaningful differences between the sample locations can be seen in the size fraction trends and polymer composition. Namely, the harbor samples had relatively larger amounts of the largest size fraction and more diversity of polymer types, which can be attributed to the urbanized activity and shorter water residence time. Power law size distribution modeling reveals deviations that help in the understanding of potential sources and removal mechanisms, although it significantly underpredicts microplastic counts for smaller-sized particles (5-45 µm), as determined by comparison with concurrently collected microplastic samples enumerated by Nile Red staining and flow cytometry.

Bovine Serum Albumin Bends Over Backward to Interact with Aged Plastics: A Model for Understanding Protein Attachment to Plastic Debris.

Plastic pollution, a major environmental crisis, has a variety of consequences for various organisms within aquatic systems. Beyond the direct toxicity, plastic pollution has the potential to absorb biological toxins and invasive microbial species. To better understand the capability of environmental plastic debris to adsorb these species, we investigated the binding of the model protein bovine serum albumin (BSA) to polyethylene (PE) films at various stages of photodegradation. Circular dichroism and fluorescence studies revealed that BSA undergoes structural rearrangement to accommodate changes to the polymer's surface characteristics (i.e., crystallinity and oxidation state) that occur as the result of photodegradation. To understand how protein structure may inform docking of whole organisms, we studied biofilm formation of bacteriaShewanella oneidensison the photodegraded PE. Interestingly, biofilms preferentially formed on the photodegraded PE that correlated with the state of weathering that induced the most significant structural rearrangement of BSA. Taken together, our work suggests that there are optimal physical and chemical properties of photodegraded polymers that predict which plastic debris will carry biochemical or microbial hitchhikers.

Rates and Predictors of Rapid Eye Movement Sleep Behavior Disorder Symptoms Among Post-9/11 Veterans.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI), which are prevalent conditions among post-9/11 veterans, increase risks of rapid eye movement (REM) sleep behavior disorder (RBD) and degenerative synucleinopathy. Rates and predictors of RBD symptoms were investigated by screening post-9/11 veterans for RBD with a validated questionnaire. METHODS: In this cross-sectional analysis, consecutive patients in the Houston Translational Research Center for TBI and Stress Disorders (TRACTS) were screened with the English translation of the RBD Questionnaire-Hong Kong (RBDQ-HK). In addition to data from the standard TRACTS battery, systematic chart review was used to identify known sleep disorders mimicking or manifesting RBD. RESULTS: Of the 119 patients with available RBDQ-HK scores, 71 (60%) and 65 (55%) screened positive for RBD, when a total score ≥21 and a factor 2 score ≥8 were used as cutoff scores, respectively. Univariable analyses with both cutoffs showed consistent associations between a positive RBDQ-HK screen and global sleep quality, number of TBI exposures, and PTSD severity. Multivariable logistic regression with total score ≥21 as a cutoff indicated that PTSD severity (odds ratio=1.06, 95% CI=1.02-1.10) and number of TBIs (odds ratio=1.63, 95% CI=1.16-2.41) were independent predictors of a positive screen, whereas global sleep quality was no longer significant. Multivariable logistic regression with factor 2 score ≥8 as a cutoff showed similar results. CONCLUSIONS: Interdisciplinary parasomnia assessment, further validation of RBD screens, and standardized reporting of REM sleep without atonia could provide necessary information on the pathophysiological relationships linking PTSD, TBI, RBD symptoms, and ultimately synucleinopathy risk among post-9/11 veterans.

Clinical Practice Patterns in Sickle Cell Disease Treatment: Disease-modifying and Potentially Curative Therapies.

Therapeutic options for sickle cell disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. This study aimed to describe practice patterns for pediatric hematologists regarding the use of disease-modifying and potentially curative therapies for SCD. A 9-section, cross-sectional electronic survey was disseminated during a 3-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology/Oncology Hemoglobinopathy Special Interest Group (ASPHO HSIG). A total of 88 physician members of the ASPHO HSIG were surveyed. Ninety percent of respondents (72/80) start hydroxyurea routinely in patients with HbSS and HbSß 0 thalassemia, regardless of disease severity. Laboratory monitoring was recommended every 3 months for stable dosing in 63.8% (51/80). New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68.5% (37/54) or crizanlizumab 93.1% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin in 65.1% (43/66) of cases. Matched sibling transplant was considered for any disease severity by 55.1% (38/69). Gene therapy trials are offered on-site by 29% (20/69). Our study demonstrated the enhanced utilization of hydroxyurea while revealing the unexplored potential of other disease-modifying therapies in SCD. These findings underscore the importance of continued knowledge acquisition about the long-term efficacy of new medical therapies and addressing barriers to the use of proven therapies and guide the development of future studies of optimal SCD management.

Endovascular Aortic Balloon control versus open Aortic cross Clamp in open ruptured abdominal Aortic aneurysm repair.

BACKGROUND: To determine 30-day mortality of endovascular aortic balloon control compared with open aortic cross clamp in open surgical repair (OSR) of ruptured abdominal aortic aneurysms (rAAAs). METHODS: A retrospective cohort review was performed of all adult patients who underwent OSR of an infrarenal rAAA between 2001 and 2018 at a single tertiary care center. A total of 174 patients were identified, of which 21 patients received endovascular aortic balloon control and 137 patients received an open aortic cross clamp. Primary outcome was 30-day mortality. Two-variable multivariate logistic regression was adjusted for preoperative blood pressure and age. RESULTS: Endovascular aortic balloon control was nonsignificantly associated with lower mortality (adjusted odds ratio [OR] = 0.75 (95% confidence interval [CI] 0.24 to 2.38), P = 0.63), and when placed under local anesthesia showed a trend toward improved mortality (adjusted OR = 0.34 (95%CI 0.06 to 1.77), P = 0.19). Balloon placement under general anesthesia was nonsignificantly associated with worse mortality (adjusted OR = 2.50 (95%CI 0.35 to 9.13), P = 0.46). CONCLUSIONS: There is no significant difference in mortality with the use of endovascular aortic balloon control in rAAA patients undergoing OSR, and it may be considered as an alternative approach to open aortic cross clamp in properly selected patients.

Prevalence and correlates of handgun carrying and perceived ease of access among adolescents in Florida.

OBJECTIVE: Adolescent firearm violence poses a serious public health concern. The aim of this study is to explore correlates of access to firearms and firearm carrying patterns among adolescents in 2022. While previous research has documented correlates and risk factors for firearm carrying, the majority of this research has relied on samples collected prior to the COVID-19 pandemic and recent shifts in national patterns of firearm violence. METHODS: We analysed data from the 2022 Florida Youth and Substance Use Survey (FYSAS) (N=41 768). Logistic regression models were used to examine associations between demographic, familial, temperamental, and behavioural factors and both ease of perceived firearm access and patterns of firearm carrying. RESULTS: The results suggest that gender, grade level, race, residential setting, having a parent in the military, delinquency, depression, bullying and substance use are associated with perceived firearm access. In addition, gender, grade level, residential setting, ease of firearm access, delinquency, substance use, and bullying are all associated with firearm carrying. CONCLUSIONS: Our findings suggest a host of demographic features and behavioural factors are associated with both perceived ease of firearm access and patterns of firearm carrying. Implications of these findings for reducing access to firearms is discussed.

Modelling the female torso and breast during physical activity: Implications on spinal loading.

Methods of modelling the female torso during physical activity often neglect the position and movement of the breast. This novel investigation compares three female torso modelling approaches that differ in complexity (integrated breast, fixed breast, dynamic breast) to determine the effect on spinal joint moments during running and jumping. The commonly used integrated breast model distributed breast mass within the torso, the fixed breast model attached the mass of the breasts to fixed positions on the anterior of the torso, and a new dynamic breast model enabled relative motion between the breasts and anterior torso. Key findings demonstrated minimal differences in lumbar spine moments (<0.05 Nm/kg; 4%) between integrated breast and fixed breast models but greater differences, up to 0.86 Nm/kg (68%) during running and 0.89 Nm/kg (82%) during jumping, when breast motion was included. Thoracic spine moments revealed similar patterns with minimal differences (<0.05 Nm/kg; 11%) between integrated breast and fixed breast models and greater differences, up to 0.48 Nm/kg (92%) during running and 0.63 Nm/kg (66%) during jumping, with the dynamic breast model. Future female musculoskeletal models should consider including breast mass and motion to avoid mis-representing spinal loading in females during running and jumping.

Traumatic stress in parents of children with congenital heart disease: a scoping review.

Congenital heart disease is the most common birth defect in the United States, with many of the affected infants requiring surgical and/or interventional procedures within their first year of life. The parental impacts of a child's diagnosis, subsequent hospitalization, and transition to home after discharge are numerous and burdensome, and many experience symptoms of traumatic stress along this trajectory. The purpose of this scoping review was to summarize current available literature related to the traumatic stress experienced by parents of children with heart disease to better understand the prevalence, related factors, and consequences. The Joanna Briggs Institute Scoping Review Framework was implemented to identify 31 relevant peer-reviewed articles published between 2000 and early 2024, including 25 quantitative studies, 3 qualitative studies, and 3 systematic reviews or meta-analyses. This scoping review provides an overview of parent traumatic stress for clinicians caring for children with heart disease at every stage of their clinical course.

Hidden support for the lionesses: a breast/bra intervention.

Despite health and performance benefits of appropriate breast support in sport, elite women athletes' knowledge of breasts/bras is poor leading to poor bra choices, breast pain and performance decrements. This multiphase intervention assessed breast/bra issues and preferences, individually prescribed sports bras and evaluated outcomes for the England Senior Women footballers. Breast/bra workshops were delivered to England players; all 36 completed pre-intervention surveys and breast/bra assessments, before being prescribed bras six weeks before European and World Championships (2022, 2023). 24 players completed post-intervention surveys. Pre-intervention outcomes identified poor knowledge, poor bra fit, many bra issues, and cultural sensitivities. Breast pain was prevalent (61%), with 25% reporting clinically significant breast pain. Post-intervention, players reported significant improvements with prescribed sports bras. 91% reported improvements in knowledge and benefiting from the intervention. This successful intervention provided an evidence-base for ongoing breast health initiatives with England Teams, plus roll-out to all levels of women's football.

Role of Bacterial Extracellular Vesicles in Manipulating Infection.

Mammalian-cell-derived extracellular vesicles, such as exosomes, have been a key focal point for investigating host-pathogen interactions and are major facilitators in modulating both bacterial and viral infection. However, in recent years, increasing attention has been given to extracellular vesicles produced by bacteria and the role they play in regulating infection and disease. Extracellular vesicles produced by pathogenic bacteria employ a myriad of strategies to assist in bacterial virulence or divert antibacterial responses away from the parental bacterium to promote infection by and survival of the parental bacterium. Commensal bacteria also produce extracellular vesicles. These vesicles can play a variety of roles during infection, depending on the bacterium, but have been primarily shown to aid the host by stimulating innate immune responses to control infection by both bacteria and viruses. This article will review the activities of bacterial extracellular vesicles known to modulate infection by bacterial and viral pathogens.

Quantification of Polymer Surface Degradation Using Fluorescence Spectroscopy.

One solution to minimizing plastic pollution is to improve reuse and recycling strategies. Recycling, however, is limited by the overall degradation of plastics being used, and current techniques for monitoring this plastic degradation fail to observe this in its early stages, which is key for optimizing reusability. This research seeks to develop an inexpensive, reproducible, and nondestructive technique for monitoring degradation of polyethylene (PE) and polypropylene (PP) materials using Nile red as a fluorescent probe. Changes in Nile red's fluorescence spectra were observed upon exposure to stained, aged PE and PP samples. As the surface hydrophobicity of the plastic decreases, Nile red's fluorescence signal undergoes a corresponding signal shift to longer wavelengths (lower energy). The trends seen in the fluorescent profile were related to more commonly used measurements of plastic degradation, namely, the carbonyl index from infrared spectroscopy and bulk crystallinity from calorimetry. Results demonstrate clear trends in fluorescence spectra shifts as related to the chemical and physical changes to the plastics, with trends dependent on the polymer type but independent of polymer film thickness. The strength of this technique is divided into two defined fits of the fluorescence signal; one fit characterizes the degradation throughout the whole range of degradative oxidation and the other is tailored to provide insight into the early stages of degradation. Overall, this work establishes a characterization tool that assesses the extent of plastics' degradation, which may ultimately impact our ability to recover plastics and minimize plastic waste.

Novel Nanoencapsulation Technology and its Potential Role in Bile Acid-Based Targeted Gene Delivery to the Inner Ear.

Hearing loss impacts a large proportion of the global population. Damage to the inner ear, in particular the sensitive hair cells, can impact individuals for the rest of their lives. There are very limited options for interventions after damage to these cells has occurred. Targeted gene delivery may provide an effective means to trigger appropriate differentiation of progenitor cells for effective replacement of these sensitive hair cells. There are several hurdles that need to be overcome to effectively deliver these genes. Nanoencapsulation technology has previously been used for the delivery of pharmaceuticals, proteins and nucleic acids, and may provide an effective means of delivering genes to trigger appropriate differentiation. This review investigates the background of hearing loss, current advancements and pitfalls of gene delivery, and how nanoencapsulation may be useful.

GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs.

BACKGROUND: Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients. METHODS: Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs. RESULTS: Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic. CONCLUSIONS: These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.