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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]

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 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]