Search

Background: Mucopolysaccharidosis (MPS) are a group of lysosomal storage diseases with substantial unmet medical needs—for both patients and caregivers. Approved therapies are limited, and the perception of investigative ones remains enigmatic. Method: Using an innovative survey concept based on the discrete choice experiment method (DEC) with neuronopathic and non-neuronopathic patient scenarios, we aimed to evaluate how parents of children with MPS perceive different approved and innovative therapies. The questionnaire was distributed via patient organizations in Germany, Switzerland, and Austria. Results: Most likely parents would choose an approach to repurposed treatments for their child (neuronopathic: 82%, 14/17 and non-neuronopathic: 94%, 16/17), followed by enzyme replacement therapy (ERT, both 88%, 15/17), hematopoietic stem cell therapy (HSCT, 70%, 12/17 and 76%, 13/17), and finally gene therapy (GT, 58%, 10/17 and 53%, 9/17). The general attitudes strongly influenced decision-making regarding treatment options. While over 80% of respondents who held a positive attitude toward ERT, HSCT, and ITTs indicated they would opt for these therapies in both neuronopathic and non-neuronopathic cases, only about half of the parents with a favorable general view of gene therapy (GT) expressed a positive perception of its likelihood as a treatment option. Furthermore, most parents found mild infections, injection site reactions (ISRs), hypertonia, and treatment-related hospitalizations acceptable and indicated patient organizations as their main source of information. Conclusions: This study provides an innovative survey method, thereby offering the rationale for a quantitative risk–benefit model and the importance of patient and caregiver-centered information dissemination, especially for innovative therapies. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases associated with reduced life expectancy and a substantial unmet medical need. Immunomodulatory drugs could be a relevant treatment approach for MPS patients, although they are not licensed for this population. Therefore, we aim to provide evidence justifying fast access to innovative individual treatment trials (ITTs) with immunomodulators and a high-quality evaluation of drug effects by implementing a risk–benefit model for MPS. The iterative methodology of our developed decision analysis framework (DAF) consists of the following steps: (i) a comprehensive literature analysis on promising treatment targets and immunomodulators for MPS; (ii) a quantitative risk–benefit assessment (RBA) of selected molecules; and (iii) allocation phenotypic profiles and a quantitative assessment. These steps allow for the personalized use of the model and are in accordance with expert and patient representatives. The following four promising immunomodulators were identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra might be the treatment of choice for patients with neurocognitive involvement. Nevertheless, a RBA should always be completed on an individual basis. Our evidence-based DAF model for ITTs directly addresses the substantial unmet medical need in MPS and characterizes a first approach toward precision medicine with immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

Bovine udder health is an important factor for animal wellbeing and the dairy farm economy. Thus, researchers aim to understand factors causing mastitis. The gold standard for diagnosing mastitis in cows is the conventional culturing of milk samples. However, during the last few years, the use of molecular methods has increased. These methods, especially sequencing, provide a deeper insight into the diversity of the bacterial community. Yet, inconsistent results regarding the mammary microbiome have been published. This study aimed to evaluate the udder health of eight dairy cows at seven days postpartum with the standard methods in veterinary practice. Additionally, swabs from the teat canal and milk samples were analyzed using 16S rRNA gene amplicon sequencing. The sensitive low-biomass milk samples displayed only a few contaminations even though they were sampled in a field environment. In healthy udders, no bacterial communities were detected by the bacterial culture nor the 16S rRNA gene amplicons. The results from the standard examination of the cows, the cell count, and the bacteriological examination were comparable with the results from 16S rRNA gene amplicon sequencing when cows displayed subclinical or latent mastitis. Besides the pathogen detected in bacterial culturing, a second bacterial strain with low but significant abundance was detected by sequencing, which might aid in the understanding of mastitis incidence. In general, molecular biological approaches might lead to promising insights into pathological events in the udder and might help to understand the pathomechanism and infection source via epidemiological analyses. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidoses (MPS) are a group of rare, heterogeneous, lysosomal storage disorders. Patients show a broad spectrum of clinical features with a substantial unmet medical need. Individual treatment trials (ITTs) might be a valid, time- and cost-efficient way to facilitate personalized medicine in the sense of drug repurposing in MPS. However, this treatment option has so far hardly been used—at least hardly been reported or published. Therefore, we aimed to investigate the awareness and utilization of ITTs among MPS clinicians, as well as the potential challenges and innovative approaches to overcome key hurdles, by using an international expert survey on ITTs, namely, ESITT. Although 74% (20/27) were familiar with the concept of ITTs, only 37% (10/27) ever used it, and subsequently only 15% (2/16) published their results. The indicated hurdles of ITTs in MPS were mainly the lack of time and know-how. An evidence-based tool, which provides resources and expertise needed for high-quality ITTs, was highly appreciated by the vast majority (89%; 23/26). The ESITT highlights a serious deficiency of ITT implementation in MPS—a promising option to improve its treatability. Furthermore, we discuss the challenges and innovative approaches to overcome key barriers to ITTs in MPS. [ABSTRACT FROM AUTHOR]

The ectoparasite Ixodes ricinus is an important vector for many tick-borne diseases (TBD) in the northern hemisphere, such as Lyme borreliosis, rickettsiosis, human granulocytic anaplasmosis, or tick-borne encephalitis virus. As climate change will lead to rising temperatures in the next years, we expect an increase in tick activity, tick population, and thus in the spread of TBD. Consequently, it has never been more critical to understand relationships within the microbial communities in ticks that might contribute to the tick's fitness and the occurrence of TBD. Therefore, we analyzed the microbiota in different tick tissues such as midgut, salivary glands, and residual tick material, as well as the microbiota in complete Ixodes ricinus ticks using 16S rRNA gene amplicon sequencing. By using a newly developed DNA extraction protocol for tick tissue samples and a self-designed mock community, we were able to detect endosymbionts and pathogens that have been described in the literature previously. Further, this study displayed the usefulness of including a mock community during bioinformatic analysis to identify essential bacteria within the tick. [ABSTRACT FROM AUTHOR]

Brown trout (Salmo trutta) is an important aquaculture species in Germany, but its production faces challenges due to global warming and a high embryo mortality. Climate factors might influence the fish's bacterial community (BC) and thus increase embryo mortality. Yet, knowledge of the physiological BC during ontogeny in general is scarce. In this project, the BC of brown trout has been investigated in a period from unfertilized egg to 95 days post fertilization (dpf) using 16S rRNA gene amplicon sequencing. Developmental changes differed between early and late ontogeny and major differences in BC occurred especially during early developmental stages. Thus, analysis was conducted separately for 0 to 67 dpf and from 67 to 95 dpf. All analyzed stages were sampled in toto to avoid bias due to different sampling methods in different developmental stages. The most abundant phylum in the BC of all developmental stages was Pseudomonadota, while only two families (Comamonadaceae and Moraxellaceae) occurred in all developmental stages. The early developmental stages until 67 dpf displayed greater shifts in their BC regarding bacterial richness, microbial diversity, and taxonomic composition. Thereafter, in the fry stages, the BC seemed to stabilize and changes were moderate. In future studies, a reduction in the sampling time frames during early development, an increase in sampling numbers, and an attempt for biological reproduction in order to characterize the causes of these variations is recommended. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storage-induced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT). [ABSTRACT FROM AUTHOR]

The article titled "An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis" has been retracted by the journal Pharmaceutics. The retraction was made due to concerns about the use of unpublished trial data without permission and potential inaccuracies in the data. The investigation confirmed that the authors did not have appropriate permission to use the trial data and that there were errors in the presentation of the data. The authors of the article have agreed to the retraction. [Extracted from the article]

Mucopolysaccharidosis (MPS) encompasses a group of genetic lysosomal storage disorders, linked to reduced life expectancy and a significant lack of effective treatment options. Immunomodulatory drugs could have the potential to be a relevant medical approach, as the accumulation of undegraded substances initiates an innate immune response, which leads to inflammation and clinical deterioration. However, immunomodulators are not licensed for this indication. Consequently, we aim to provide evidence advocating fast access to innovative individual treatment trials (ITTs) with immunomodulatory drugs and high-quality evaluation of drug effects by implementing a risk-benefit model tailored for MPS. The iterative methodology of our novel decision analysis framework (DAF) involves three key steps: (i) literature review on promising treatment targets and immunomodulators in MPS; (ii) quantitative risk-benefit assessment (RBA) of selected molecules; (iii) assigning phenotypic profiles and quantitative evaluations. The results facilitate a personalized application of the model and are based on published evidence as well as interdisciplinary experts' consensus and patient perspectives. Four promising immunomodulators have been identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra is anticipated as a treatment of choice for neuronopathic MPS patients. Nevertheless, a comprehensive RBA should always be completed on an individual basis. Our evidence-based DAF tool for ITTs directly addresses the substantial unmet medical need in MPS and characterizes an initial stride toward precision medicine with immunomodulators., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Lyme borreliosis is a vector-borne disease in humans and animals caused by bacteria from the Borrelia burgdorferi sensu lato complex ( Bb sl). The possible transmission of Bb sl from companion animals to humans via ticks makes this disease important in terms of One Health approaches. Thus, early and accurate diagnosis and treatment are of utmost importance. Today's standard for the detection of specific antibodies against Bb sl is a two-tiered test system based on an ELISA for screening combined with a line immunoassay (LIA) for confirmation. In this study, 200 canine and 200 equine serum samples with known antibody status were tested with two different LIAs (A and B). Results were compared regarding sensitivity, specificity, the diagnostic outcome for dogs and horses, as well as operability of the test. The results for canine serum samples corresponded to 94.0%, making both LIAs a good choice for LB diagnostic in dogs. For equine serum samples, the agreement of both tests was 65.5%, displaying the challenge equine samples still provide in LB diagnostic. Major concerns were the interpretation of the OspA antigen (AG) signal and the use of unspecific (i.e., p100/p83) or too sensitive signals on the LIA. The operability of both LIAs was equally user-friendly. Regarding the tests' evaluation, the scanning process provided by LIA A was a major advantage considering the comparability of the tests.