Biology subjects

Hoffman, J.

Publications and source records attributed to Hoffman, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones

Multiple myeloma (MM) is a genomically complex malignancy of terminally differentiated plasma cells. Here, we have utilized the SCID-rab patient derived xenograft (PDX) model as a platform to expand scarce primary MM samples across disease stages and major cytogenetic subgroups for comprehensive molecular analysis. The model generated abundant CD138+ cells while retaining key genomic, transcriptomic and proteomic features of corresponding patient tumors. Compared with human myeloma cell lines, PDX cells more closely resembled primary MM in proliferative state and expression of therapeutically relevant targets. WGS and single cell WGS showed that PDXs arose from the selection of pre-existing subclones, including clones harboring high-risk alterations and convergent mechanisms of tumor suppressor inactivation. These findings establish SCID-rab PDX models as a platform for multiomic profiling, studies of clonal evolution, and determining therapeutic response in MM.

cancer biology↗

bioRxiv2026

ZNF217 promotes receptor tyrosine kinase plasticity and AXL-ERK dependency in ovarian cancer

ZNF217 is a potent oncogene that drives ovarian cancer progression and therapeutic resistance. We show that ZNF217 overexpression markedly increases ERBB2 levels in ovarian cancer cells, suggesting its potential as a biomarker to identify ovarian tumors that will respond to ERBB2-targeted therapeutics. Unexpectedly, ZNF217-high ovarian cancer cells exhibit resistance to multiple ERBB2 inhibitors, revealing a disconnect between receptor abundance and drug sensitivity. Mechanistically, ZNF217 drives chemoresistance by elevating the expression of several key receptor tyrosine kinases, most notably AXL, that activates MAPK signaling. Further, ZNF217 also upregulates ERK1/2 levels in ovarian cancer cells. This induces rewiring of downstream signaling, promoting an ERK-dominant state that sustains survival despite ERBB2 inhibition. Therapeutic targeting of the AXL-ERK axis reduced cell viability and metastatic potential in vitro, while suppressing tumor burden and prolonging survival in xenograft models. Thus, by elevating the expression of several key signaling receptors and their downstream effectors in ovarian cancer cells, ZNF217 establishes signaling plasticity that defines a novel mechanism of chemoresistance. These findings identify ZNF217 as a key determinant of signaling state and drug response and provides rationale to evaluate targeting AXL and ERK signaling in ZNF217-high ovarian tumors.

cancer biology↗

bioRxiv2026

Evaluating performance bias in face-to-BMI vision transformer models across diverse human populations

Computer vision models that estimate body mass index (BMI) from facial features offer a non-invasive, low-cost alternative to physical measurement, with uses in telemedicine, emergency care where a scale or measuring tools arent available, automated self-monitoring, and large-scale epidemiological research. Most of these models, however, are trained on government records, social media images, and celebrity photographs, sources that introduce dataset biases and fail to represent the general public. This study tests how well a face-to-BMI machine learning model generalizes across populations, specifically how morphological diversity and population-specific training data affect cross-cultural accuracy. We trained and evaluated Vision Transformer (ViT-H/14) models on paired BMI measurements and facial photographs from four Indigenous populations: the Orang Asli of Malaysia, the Ju/hoansi of Southern Africa, the Sama residing in the Philippines, and the Tsimane of Bolivia. To evaluate how training data composition affects predictions, we compared four training strategies, from single-population models (focal models) to models trained on the full combined global dataset (global models). In-distribution training always produced the best performance. Models exposed to a target populations morphology, whether focal or global, consistently predicted BMI most accurately for that population. But when a target population differed from the training sample, adding more cross-cultural variation to training improved out-of-distribution predictions. Therefore, training on a populations own data works best when that data exists, and training on data spanning a wide range of human morphology is the strongest fallback when it doesnt. These findings suggest that while target population training data produces the most accurate results, training on datasets that capture global morphological variation substantially improves performance in unrepresented populations. Broader diversity in training data is essential for developing machine learning health tools that generalize reliably across human populations.

bioinformatics↗

bioRxiv2026

High population density limits predator access in Antarctic fur seal breeding colonies

Population density can influence individual predation risk in colonial breeders through shared vigilance and predator deterrence. We investigated how predator-prey interactions are shaped by population density at two Antarctic fur seal (Arctocephalus gazella) breeding colonies at Bird Island, South Georgia, which differ four-fold in seal density. By deploying autonomous time-lapse cameras, we captured high-resolution images at one-minute intervals throughout the breeding season. Using a YOLOv8 neural network, we identified fur seal adult males, females and pups, as well as three predator-scavenger bird species: giant petrels (Macronectes spp.), brown skuas (Stercorarius antarcticus) and snowy sheathbills (Chionis alba). Abundance patterns corresponded to the known foraging and breeding behaviours of these species. Differences in seal density between the colonies were mainly driven by adult females and their pups, but not adult males. The ratios of predatory birds to pups were markedly lower at the high-density colony, while scavenger to pup ratios remained similar. Spatial analyses revealed that predators were largely excluded from areas of high seal density, whereas scavengers overlapped extensively with pups in both colonies. This study demonstrates the value of remote observation in resolving predator-prey interactions and illustrates how density can shape predation risk in a colonial breeder.

ecology↗

bioRxiv2026

Sensitivity profiling reveals consistent drug responses across preclinical neuroblastoma models

Despite intensive treatment, overall survival for high-risk and relapse neuroblastoma patients remains below 50%. Even though comprehensive molecular profiling enables treatment stratification, druggable alterations have been identified for only a subset of patients. In vitro drug screening offers a complementary approach. Here, we compare the translational potential of three preclinical drug screening methods: ex vivo short-term, in vitro patient-derived organoid and in vivo patient-derived xenograft (PDX) drug testing. In total, 55 screens were performed from 38 neuroblastoma samples and five pediatric non-malignant samples, testing 77-224 drugs per screen. Ex vivo short-term drug screens achieved higher success rates than organoid screens (65% versus 23%) and shorter turnaround times (14 days versus 3-12 months). Matched samples showed consistent drug sensitivities across sample origin (patient versus PDX-derived; mean r = 0.84) and method (ex vivo short-term versus organoids; mean r = 0.87), demonstrating that ex vivo short-term screens recapitulate drug sensitivities found in long-term organoid models. In parallel, as part of the ITCC-P4 consortium, ten compounds were tested in vivo in eight PDX models, with samples matching the ex vivo screens. For seven out of ten clinically available compounds, ex vivo drug responses were comparable with in vivo responses in matched PDX models. These results demonstrate that, while organoids and PDX models remain essential for drug discovery, ex vivo short-term drug screening provides a rapid alternative for functional precision oncology in neuroblastoma.

cell biology↗

bioRxiv2025

Predicting porcini: a decade of sporocarp monitoring reveals the meteorological triggers of Boletus edulis fruiting in central European beech forests

Despite recent molecular and genomic advances, the reproductive biology of ectomycorrhizal fungi (EMF) remains poorly understood. In particular, the meteorological cues triggering sporocarp formation remain largely unknown, limiting our ability to induce fruiting in the laboratory. To address this knowledge gap, we analysed a decade-long (2015-2024) dataset of daily, near-exhaustive sporocarp observations from an intensively monitored population of Boletus edulis in a central European beech forest near Bielefeld, Germany. Using generalised linear mixed-effect models, we estimated the lagged effects of temperature and precipitation on sporocarp formation and identified the conditions associated with peak fruiting. Although sporocarps formed across a broad range of conditions, peak fruiting was associated with a mean temperature of approximately 13{degrees}C averaged over the preceding 20 days and increased linearly with precipitation accumulated over a 26-day window. Under projected warmer and drier autumn conditions, B. edulis sporocarp formation in European beech forests is likely to decline.

ecology↗

bioRxiv2025

What determines trophic niche breadth? A global analysis of freshwater fishes using isospaces

Trophic niche is one of the most tractable dimensions of a species niche. Several hypotheses have been proposed to explain global variation in species trophic niches, but empirical tests are limited. Stable isotope analysis (SIA) of {delta}{superscript 1}3C (a proxy for basal sources) and {delta}{superscript 1} N (a proxy for vertical trophic position) has increasingly been used to estimate trophic niche variation. We performed SIA on a dataset of over 33,000 stable isotope samples from freshwater fishes across six ecoregions. For 541 populations (358 species), we estimated the size of {delta}{superscript 1}3C x {delta}{superscript 1} N isospace--a bivariate representation of trophic niche breadth. We evaluated isospace variation in relation to environmental factors, species traits, and sampling scale, testing both novel and long-standing hypotheses about the drivers of trophic niche variation. A Boosted Regression Tree Model best predicted isospace, with environmental and trait-based variables among the strongest predictors. Fish isospaces were broader in regions with warmer temperatures, higher humidity, and precipitation variability, suggesting that more productive, diverse, and seasonal ecosystems are associated with broader trophic niches. Conversely, isospace size declined with increasing basin fish richness, which may reflect heightened interspecific competition or historical competitive exclusion. Isospace size was slightly smaller in large lakes compared to rivers, streams, and small lakes. Within-population variation in body size was strongly and positively associated with isospace size, highlighting the role of ontogenetic dietary shifts. Fish with truncate-rounded fins had broader isospaces than those with forked-lunate fins, likely due to the former having more limited movement and greater spatial isolation that resulted in greater between-individual niche variation. Primary consumers had larger isospaces than intermediate and top consumers. Predators showed relationships consistent those observed from analysis encompassing all trophic guilds, but non-predators deviated with regards to four variables--solar radiation, basin richness, average body size, and caudal fin aspect ratio. Isospace size increased with the number of sampled individuals, habitats and years surveyed. Although isospace patterns have well-documented limitations as trophic ecology metrics, our findings nonetheless conform with several longstanding hypotheses for trophic niche variation and stimulate new ideas about environmental and biological drivers of niche breadth.

ecology↗

bioRxiv2025

The "Grove-First" Framework: Starting in the Grove to Find Therapies for Huanglongbing

Citrus greening disease, also known as huanglongbing (HLB), is the most serious vector-borne bacterial disease of citrus world-wide1,2. There is an immediate global need to provide the citrus industry with relief from HLB and a return to profitable citrus production. Standard screening methods for HLB therapeutic treatments typically involve various laboratory-based assays to select treatments with antimicrobial properties3, which then advance to greenhouse and eventually field testing in a workflow that takes multiple years. Unlike traditional lab-first screening, we present a design of experiments framework4,5, referred to as Grove-First, that rapidly screens treatments with regulatory-friendly profiles in commercial citrus groves using trunk injection to select treatments that improve tree health and fruit yield over the course of a single growing season. Using this framework, we identified candidate treatments with effects comparable to or better than the standard oxytetracycline (OTC) on visual tree-health and/or yield indices in an initial screen of HLB-positive 8-year-old Valencia sweet orange trees. Expanded trials in commercial citrus groves allowed us to validate the initial screening results at other locations and in other citrus varieties. Grove-First rapidly accelerated the identification and large-scale field testing of HLB therapies, some of which are available for growers to use immediately and others that require further field testing and/or regulatory actions.

plant biology↗

bioRxiv2025

Sequencing by Expansion (SBX) -- a novel, high-throughput single-molecule sequencing technology

Remarkable advances in high-throughput sequencing have enabled major biological discoveries and clinical applications, but achieving wider distribution and use depends critically on further improvements in scale and cost reduction. Nanopore sequencing has long held the promise for such progress, but has had limited market penetration. This is because efficient and accurate nanopore sequencing of nucleic acids has been challenged by fundamental signal-to-noise limitations resulting from the poor spatial resolution and molecular distinction of nucleobases. Here, we describe Sequencing by Expansion (SBX), a single-molecule sequencing technology that overcomes these limitations by using a biochemical conversion process to encode the sequence of a target nucleic acid molecule into an Xpandomer, a highly measurable surrogate polymer. Expanding over 50 times longer than the parent DNA templates, Xpandomers are engineered with high signal-to-noise reporter codes to enable facile, high-accuracy nanopore sequencing. We demonstrate the performance of SBX and present the specialized molecular structures, chemistries, enzymes and methods that enable it. The innovative molecular and systems engineering in SBX create a transformative technology to address the needs of existing and emerging sequencing applications.

genomics↗

bioRxiv2024

Sustainability in the laboratory: evaluating the reuseability of microtiter plates for PCR and fragment detection

1.Single-use plastics (SUPs) are indispensable in laboratory research, but their disposal contributes substantially to environmental pollution. Consequently, reusing common SUP items such as microtiter plates represents a promising strategy for improving laboratory sustainability. However, the key challenge lies in determining whether SUP reuse can be implemented without sacrificing data quality. To investigate this, we conducted a simple experiment to assess the impact of reusing microtiter plates on microsatellite genotyping accuracy. Plates previously used for PCR and fragment detection were cleaned opting for an environmentally friendly approach using regular soap and then reused. Our results indicate that, while reusing PCR plates significantly increases genotyping error rates due to residual DNA contamination, detection plates can be reused without compromising data quality. Our approach offers laboratories a practical and sustainable option for reducing SUP waste and costs while maintaining research integrity.

molecular biology↗

bioRxiv2024

3D spatial distribution of Sost mRNA and Sclerostin expression in response to in vivo mechanical loading

Bones adapt to external mechanical loads through a process known as mechanoadaptation. Osteocytes are the bone cells that sense the mechanical environment and initiate a biological response. Investigating the changes in osteocyte molecular expression following mechanical loading has been instrumental in characterizing the regulatory pathways involved in bone adaptation. However, current methods for examining osteocyte molecular expression do not preserve the three-dimensional structure of the bone, which plays a critical role in the mechanical stimuli sensed by the osteocytes and their spatially controlled biological responses. In this study, we used WISH-BONE to investigate the spatial distribution of Sost-mRNA transcripts and its encoded protein, sclerostin, in 3D mouse tibia midshaft following in vivo tibia loading. Our findings showed a decrease in the percentage of Sost-positive osteocytes predominantly at 25% and 37% of the bone length, and in the posterior-lateral side of the tibia after loading. Sclerostin-positive osteocytes in the loaded legs were found to be similar to the contralateral legs after 2 weeks of loading. This work is the first to provide a 3D analysis of Sost and sclerostin distribution in loaded versus contralateral mouse tibia midshafts. It also highlights the importance of the bone region analyzed and the method utilized when interpreting mechanoadaptation results. WISH-BONE represents a powerful tool for further characterization of mechanosensitive genes regulation in bone and holds potential for advancing the development of new treatments targeting mechanosensitivity-related bone disorders.

bioengineering↗

bioRxiv2024

Operant alcohol self-administration targets GluA2-containing AMPAR expression and synaptic activity in the nucleus accumbens in a manner that drives the reinforcing properties of the drug

Rationale: The positive reinforcing effects of alcohol (ethanol) drive its repetitive use and contribute to alcohol use disorder (AUD). Ethanol alters the expression of glutamate AMPA receptor (AMPAR) subunits in reward-related brain regions, but the extent to which this effect regulates ethanols reinforcing properties is unclear. Objective: This study investigates whether ethanol self-administration changes AMPAR subunit expression and synaptic activity in the nucleus accumbens core (AcbC) to regulate ethanols reinforcing effects in male C57BL/6J mice. Results: Sucrose-sweetened ethanol self-administration (0.81 g/kg/day) increased AMPAR GluA2 protein expression in the AcbC, without effect on GluA1, compared to sucrose-only controls. Infusion of myristoylated Pep2m in the AcbC, which blocks GluA2 binding to N-ethylmaleimide-sensitive fusion protein (NSF) and reduces GluA2-containing AMPAR activity, reduced ethanol-reinforced responding without affecting sucrose-only self-administration or motor activity. Antagonizing GluA2-lacking AMPARs, through AcbC infusion of NASPM, had no effect on ethanol self-administration. AcbC neurons receiving projections from the basolateral amygdala (BLA) showed increased sEPSC area under the curve (a measurement of charge transfer) and slower decay kinetics in ethanol self-administering mice as compared to sucrose. Optogenetic activation of these neurons revealed an ethanol-enhanced AMPA/NMDA ratio and significantly reduced paired-pulse ratio, suggesting elevated GluA2 contributions specifically within the BLA[->]AcbC pathway. Conclusions: Ethanol use upregulates GluA2 protein expression in the AcbC and AMPAR synaptic activity in AcbC neurons receiving BLA projections and enhances synaptic plasticity directly within the BLA[->]AcbC circuit. GluA2-containing AMPAR activity in the AcbC regulates the positive reinforcing effects of ethanol through an NSF-dependent mechanism, highlighting a potential therapeutic target in AUD.

neuroscience↗

bioRxiv2024

Woman the Hunter? Female foragers sometimes hunt, yet gendered divisions of labor are real

Gendered divisions of labor are a feature of every known contemporary hunter-gatherer (forager) society. While gender roles are certainly flexible, and prominent and well-studied cases of female hunting do exist, it is more often men who hunt. A new study (Anderson et al., 2023) surveyed ethnographically known foragers and found that women hunt in 79% of foraging societies, with big-game hunting occurring in 33%. Based on this single type of labor, which is one among dozens performed in foraging societies, the authors question the existence of gendered division of labor altogether. As a diverse group of hunter-gatherer experts, we find that claims that foraging societies lack or have weak gendered divisions of labor are contradicted by empirical evidence. We conducted an in-depth examination of Anderson et al. (2023) data and methods, finding evidence of sample selection bias and numerous coding errors undermining the papers conclusions. Anderson et al. (2023) have started a useful dialogue to ameliorate the popular misconception that women never hunt. However, their analysis does not contradict the wide body of empirical evidence for gendered divisions of labor in foraging societies. Furthermore, a myopic focus on hunting diminishes the value of contributions that take different forms and downplays the trade-offs foragers of both sexes routinely face. We caution against ethnographic revisionism that projects Westernized conceptions of labor and its value onto foraging societies.

evolutionary biology↗

bioRxiv2024

Prelude to Malignancy: A Gene Expression Signature in Normal Mammary Gland from Breast Cancer Patients Suggests Pre-tumorous Alterations and Is Associated with Adverse Outcomes

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes is still missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

genomics↗

bioRxiv2023

GTExome: Modeling commonly expressed missense mutations in the human genome

A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability. Information about the consequences of each mutation is provided to the user including if disulfide bonds, hydrogen bonds, or salt bridges are broken, buried prolines introduced, buried charges are created or lost, charge is swapped, a buried glycine is replaced, or if the residue that would be removed is a proline in the cis configuration. Also, if the mutation site is in a binding pocket the number of pockets and their volumes are reported. The user can assess this information and then select from available experimental or computationally predicted structures of native proteins to create, visualize, and download a model of the mutated protein using Fast and Accurate Side-chain Protein Repacking (FASPR). For AlphaFold modeled proteins, confidence scores for native proteins are provided. Using this tool, we explored a set of 9,666 common missense mutations from a variety of tissues from GTEx and show that most mutations can be modeled using this tool to facilitate studies of proteinprotein and protein-drug interactions. The open-source tool is freely available at https://pharmacogenomics.clas.ucdenver.edu/gtexome/ Author SummaryGTExome greatly simplifies the process of studying the three-dimensional structures of proteins containing missense mutations that are critical to understanding human health. In contrast to current state-of-the-art methods, users with no external software or specialized training can rapidly produce three-dimensional structures of any possible mutation in nearly any protein in the human exome. Accomplishing this requires reliance on AlphaFold based structural models. We therefore compared the protein models created by GTExome where possible to known experimental structures. We find that by avoiding specific mutations, the majority of proteins are amenable to being modeled by GTExome with similar results to the direct use of AlphaFold.

bioinformatics↗

bioRxiv2023

Regulation of Chromatin Architecture by Transcription Factor Binding

Transcription factors (TF) bind to chromatin and regulate the expression of genes. The pair Myc:Max binds to E-box regulatory DNA elements throughout the genome, controlling transcription of a large group of specific genes. We introduce an implicit modeling protocol for Myc:Max binding to mesoscale chromatin fibers to determine TF effect on chromatin architecture and shed light on its mechanism of gene regulation. We first bind Myc:Max to different chromatin locations and show how it can direct fiber folding and formation of microdomains, and how this depends on the linker DNA length. Second, by simulating increasing concentrations of Myc:Max binding to fibers that differ in the DNA linker length, linker histone density, and acetylation levels, we assess the interplay between Myc:Max and other chromatin internal parameters. Third, we study the mechanism of gene silencing by Myc:Max binding to the Eed gene loci. Overall, our results show how chromatin architecture can be regulated by TF binding. The position of TF binding dictates the formation of microdomains that appear visible only at the ensemble level. On the other hand, the presence of linker histone, acetylations, or different linker DNA lengths regulates the concentration-dependent effect of TF binding. Furthermore, we show how TF binding can repress gene expression by increasing fiber folding motifs that help compact and occlude the promoter region. Importantly, this effect can be reversed by increasing linker histone density. Overall, these results shed light on the epigenetic control of the genome dictated by TF binding.

genomics↗

bioRxiv2023

Long-term selection on mitocoding genes buried in mammalian and avian nuclear genomes

Sporadically genetic material that originates from an organelle genome integrates into the nuclear genome. However it is unclear what processes maintain such an integration over longer evolutionary time. Recently it was shown that nuclear DNA of mitochondrial origin (NUMTs) may harbour genes with intact mitochondrial reading frames despite the fact that they are highly divergent to the hosts mitochondrial genome. Two major hypotheses have been put forward to explain the existence of such mitocoding nuclear genes: (A) recent introgression from another species and (B) long-term selection. To address whether these intriguing possibilities do play a role we scanned the genomes of more than 1,000 avian and mammalian species for NUMTs. We indeed identified that the subclass of divergent NUMTs harbouring mitogenes with intact reading frames are widespread across mammals and birds. We can show that for these NUMTs signatures of cross-species introgression are widespread in birds, but not mammals with the exception of ungulates. We can also show that a substantial fraction of deeply divergent NUMTs are maintained by selection. For a small number of NUMT genes we identify an evolutionary signature that is consistent with adaptive evolution including one human NUMT that is shared among seven ape species. This highlights the intriguing possibility that NUMT insertions occasionally may be functional.

evolutionary biology↗

bioRxiv2020

Asprosin Neutralizing Antibodies as a Treatment for Metabolic Syndrome

Recently, we discovered a new glucogenic and centrally-acting orexigenic hormone - asprosin. Asprosin is elevated in metabolic syndrome (MS) patients, and importantly, its genetic loss results in reduced appetite, leanness and robust insulin sensitivity, leading to protection from MS. Here we demonstrate that anti-asprosin monoclonal antibodies (mAbs) are a dual-effect pharmacologic therapy that targets the two key pillars of MS - over-nutrition and the blood glucose burden. Anti-asprosin mAbs from three distinct species lowered appetite and body weight, and improved blood glucose in a dose-dependent and epitope-agnostic fashion in three independent MS mouse models, with an IC50 of [~]1.5 mg/kg. In addition, mAb treatment ameliorated MS associated dyslipidemia and hepatic dysfunction. The mAbs displayed half-life of over 3 days in vivo, with equilibrium dissociation-constants in picomolar to low nanomolar range. This evidence paves the way for further development towards an investigational new drug application and subsequent human trials for treatment of MS, a defining physical ailment of our time.

physiology↗