Repurposing of authorised medicines has been under discussion for a long time. Drug repurposing is the process of identifying a new use for an existing medicine in an indication outside the scope of the original approved indication. Indeed, the COVID-19 health crisis has brought the concept to the frontline by proving the usefulness of this practise in favour of patients for an early access to treatment. Under the umbrella of the Pharmaceutical Committee and as a result of the discussions at the European Commission Expert Group on Safe and Timely Access to Medicines for Patients (STAMP) a virtual Repurposing Observatory Group (RepOG) was set up in 2019 to define and test the practical aspects of a pilot project thought to provide support to "not-for-profit" stakeholders generating or gathering data for a new therapeutic use for an authorised medicine. The group's initial plan was impacted by the outbreak of the SARS-CoV-2 pandemic and the launch of the pilot needed to be postponed. This article describes the progress and the activities conducted by the group during this past and yet extraordinary 2020-2021 to keep the project alive and explores on the background of this topic together with the obvious opportunities this health crisis has brought up in terms of repurposing of medicines.
- Publikační typ
- časopisecké články MeSH
Advanced therapy medicinal products (ATMPs) represent a new generation of biopharmaceuticals that comprise gene therapy medicinal products (GTMPs), somatic cell therapy products (CTMPs), tissue engineered products (TEPs), and combined advanced therapy medicinal products (cATMPs). The joint effort of the academia-industry-regulatory triangle translated scientific progress into ten authorized ATMPs in the European Community. This notion holds promise for the whole field of ATMP therapies that have been increasingly evaluated in a number of clinical studies, also in the Czech Republic (CR). Here, we prepared an overview of regulatory framework, past and present clinical studies, and already authorized ATMPs in the CR. Clinical studies on ATMPs in the CR were mapped using public databases, particularly ClinicalTrials.gov, the European Union Clinical Trials Register, and the State Institute for Drug Control database. We found 50 registered clinical studies using ATMPs in the CR that mostly involve CTMPs (n = 36), followed by GTMPs (n = 4) and TEPs (n = 4). The majority of the studies use autologous ATMPs (76%) and are aimed at the treatment of oncologic conditions (58%) and musculoskeletal disorders (24%). The most frequent autologous cell type was dendritic cells (42%), bone marrow mononuclear cells (16%) and bone marrow mesenchymal stromal cells (13%). Allogeneic ATMPs (12%) are mostly aimed at the treatment of venous ulcers (33%) and utilize keratinocytes and fibroblasts (33%). In summary, ATMPs are increasingly tested in clinical trials in the CR, which will most likely lead to their translation into broader clinical use. However, to stimulate market viability of registered ATMPs, implementation of the sophisticated reimbursement system will be required.
- MeSH
- biologické přípravky terapeutické užití MeSH
- buněčná a tkáňová terapie trendy MeSH
- Evropská unie MeSH
- genetická terapie trendy MeSH
- lidé MeSH
- tkáňové inženýrství trendy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
The research and development of advanced therapy medicinal products (ATMPs) has been active in Europe and worldwide during recent years. Yet, the number of licensed products remains low. The main expected legal change in the near future in the European Union (EU) concerns the regulation on clinical trials (536/2014), which will come into force in 2018. With this new framework, a more harmonized and swift process for approval of clinical trials is anticipated, which is expected to support the entry of new innovations into the EU market. A survey on ATMPs in clinical trials during 2010-2015 in the EU was conducted in order to study the trends of ATMP development since the earlier survey published in 2012. According to the results, the number of clinical trials using ATMPs is slowly increasing in the EU. Yet, the focus is still in early development, and the projects are mainly carried out by small and medium-sized enterprises, academia, and hospitals. Oncology is the main area of clinical development. Yet, the balance between cell-based products and gene therapy medicinal products in this area may be changing in the future due to the new T-cell technologies. Many limitations and challenges are identified for ATMP development, requiring proportionate regulatory requirements. On the other hand, for such a novel field, the developers should be active in considering possible constraints and actively engage with authorities to look for solutions. This article provides up to-date information on forthcoming regulatory improvements and discusses the main challenges hampering the commercialization of ATMPs in the EU.
- MeSH
- biomedicínský výzkum ekonomika zákonodárství a právo normy MeSH
- Evropská unie MeSH
- farmaceutický průmysl ekonomika zákonodárství a právo normy MeSH
- klinické zkoušky jako téma ekonomika zákonodárství a právo normy MeSH
- transfer technologií * MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
For teeth as for any organ, knowledge of normal development is essential for the proper interpretation of developmental anomalies in mutant mice. It is generally accepted that tooth formation is initiated with a single signaling center that, in the incisor region, is exclusively related to the development of the functional adult incisor. Here, using a unique combination of computer-aided three-dimensional reconstructions and whole mount in situ hybridization of mandibles from finely staged wild-type mouse embryos, we demonstrate that several Sonic hedgehog (Shh) expression domains sequentially appear in the lower incisor region during early development. In contrast to the single Shh expression domain that is widely assumed to be present in each lower incisor area at ED12.5-13.5, we identified two spatially distinct regions of Shh expression that appear in an anterior-posterior sequence during this period. The initial anterior, more superficially located Shh expression region represented the rudimentary (so-called deciduous) incisor, whereas only the later posterior deeper situated region corresponded to the prospective functional incisor. In the more advanced embryos, only this posterior Shh expression in the incisor bud was detectable as a precursor of the enamel knot. This study offers a new interpretation of published molecular data on the mouse incisor from initiation through ED13.5. We suggest that, as with Shh expression, other molecular data that have been ascribed to the progressive development of the mouse functional incisor at early stages, in fact, correspond to a rudimentary incisor whose development is aborted.
- MeSH
- čelisti embryologie metabolismus MeSH
- embryonální vývoj MeSH
- epitel metabolismus MeSH
- myši transgenní MeSH
- myši MeSH
- proteiny hedgehog genetika metabolismus MeSH
- řezáky embryologie metabolismus MeSH
- trans-aktivátory genetika metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
