Therapy Accelerator for Rare Diseases

Preclinical models

In Vitro Models

The search for effective treatments often begins with a deeper understanding of the disease itself. In the lab, we can use cell models to identify the molecular and immunological causes of a disease. By recreating disease conditions in vitro, researchers can explore the underlying mechanisms and test potential therapies. An ideal cell model accurately reflects the disease phenotype and serves as a predictive tool for therapy development.

Therapy Development

To create a “molecular fingerprint” of a disease, we use a variety of techniques, including genomic analysis, proteomics, metabolomics, and transcriptomics. Once we understand the cellular malfunctions, we can begin developing targeted treatments. These treatments may involve dietary supplements, drug repurposing (identifying known compounds that might work for new purposes), or the development of cell or gene therapies specific to the disease. Initially, we test and optimize these therapies on cell models. If successful, further testing in animal models may follow before moving to human trials. Our long-term goal is to enhance the predictive power of in vitro models so that, in the future, animal testing may no longer be necessary for efficacy and toxicity assessments.

Leveraging Existing Expertise

At Radboudumc, multiple groups are already developing in vitro models for different diseases. By collaborating across departments, we aim to enhance existing models and increase the availability of advanced in vitro systems, including organ-on-a-chip technology. Our goal is to foster a supportive, collaborative environment that maximizes the use of our current infrastructure and resources.

Clinical translation of Cell- and Gene therapies

Genetic therapies

Genetic therapies are defined by a therapeutic strategy that aims to correct the pathological consequences of a genetic defect underlying disease. While these defects typically reside within the genomic DNA, pathological effects are usually caused by aberrant RNA and/or protein production. Consequently, the correction of such defects can occur at the DNA level (e.g. gene augmentation, genome editing), RNA level (e.g. splicing modulation, allele-specific transcript degradation, RNA editing) or protein level (enzyme replacement), delivery being a shared challenge. Several groups within the Radboudumc are experts for one or more of the aforementioned strategies, aiming at treating or curing specific rare diseases. The selection which approach is most suitable for a given disease depends on many factors including the genetic defect, its pathophysiological consequences at the molecular level and the ease with which therapeutic molecules can be delivered to the target cells within the human body or ex vivo. In addition, access to model systems for preclinical assessment of therapeutic strategies and biomarkers to detect and quantify treatment responses is crucial.

Cell-based therapies

In cell-based therapies, living cells from a patient or donor are used to provide therapy for various conditions. Cell-based therapies can be performed with unmodified cells directly harvested from the patient or healthy donor, but these may also be expanded, activated and/or genetically modified to increase their specificity and efficacy. Currently, different cell types, including stem cells, T cells, dendritic cells and NK cells, are used for specific targets in patients. Furthermore, various developments are aimed at using immune cells that can specifically recognize and destroy cancer cells. Within Radboudumc, initiatives in the field of cell-based therapies have been brought from the laboratory to the clinic for many years. The most active departments in this area are Medical BioSciences (MBS) and the Laboratory of Hematology from the department of Laboratory Medicine in close collaboration with the department of Pharmacy and several clinical departments, e.g. Hematology, Medical Oncology, Gynecology, Human Genetics, Gastroenterology and other departments treating oncology patients
Gene- and cell therapies are advanced therapy medicinal products (ATMPs). At Radboudumc, we have established an excellent infrastructure to translate preclinical findings with ATMPs into the clinic. This includes support for (pre)clinical product development and a fully operational GMP facility that is licensed and equipped for manufacturing and QC of cell-based ATMPs as investigational products. 

Innovative clinical trial design

Many rare diseases currently have no treatment, but regulators require the same high-quality evidence for approval as for more common diseases. Therefore, a major challenge in the evaluation of potential therapies for rare diseases is the scarcity of data (small patient populations) combined with heterogeneity in patient characteristics and responses.

Innovative study designs and methods are needed to assess the safety and efficacy of these potential therapies. We are focusing on promising innovative designs such as platform trials, adaptive trials, and personalised n=1 trials, combined with the most beneficial patient selection and outcomes, to accelerate the development of therapies for rare diseases.

Master track 'Therapy Development'

There is a significant need to train (Biomedical Sciences) students in developing drug, cell- and gene-based therapies from a preclinical, clinical, and regulatory perspective. To address this need, a new BMS master specialisation ‘Therapy Development’ will be developed.

About the specialisation

Developing therapies for rare diseases requires a comprehensive understanding of advanced science and technology as well as the complexities that these diseases present. The new specialisation covers all aspects of traditional therapy development, with an accent on tailoring this for rare diseases. With this specialisation, we aim to create a clear path for students interested in therapy development. This will additionally help in strengthening the capacity within Radboudumc to train professionals who can connect research, drug development and valorisation to accelerate the advancement of drug, cell- and gene-based therapies.

BMS Master’s programme

Do you want to know more about the Biomedical Sciences Master’s programme? Check this webpage.

Training professionals

More information about this specific topic will follow soon.

Internal External networks

The rapidly evolving landscape of rare disease therapy development necessitates a collaborative and sustainable approach to address the unique challenges in this field. A number of initiatives aim for a value-based and sustainable business model for rare diseases medicines, which fits with Radboudumc’s mission. Such networks are also highly valuable to showcase Radboudumc's expertise to sustain and expand relevant collaborations and to increase access to expert knowledge on therapy development that is currently missing. By strengthening local, national and international connections and participating in national and international initiatives and public-private partnerships, Radboudumc researchers can make significant contributions to improving the lives of patients with rare disease. This will allow them to effectively influence the field of rare disease therapy development and contribute to Radboudumc's position as a leading institution in this domain.

Within the Radboudumc, the Therapy Accelerator for Rare Diseases aims accelerate rare disease therapy development by promoting exchange of expertise and infrastructure, and by developing of novel research projects and partnerships. To achieve this, we foster and support learning communities and connect researchers with relevant private parties. Regionally, the Therapy Accelerator team represents Radboudumc within Pharma Delta, a public-private ecosystem of knowledge institutes, governments and pharma and biotech companies within the Nijmegen/Oss/Boxmeer region. At the national level, together with Nationaal Farmaceutisch kennisccentrum at LUMC and Medicijn voor Maatschappij at AmsterdamUMC we have initiated RARE-NL to support drug repurposing and rare disease therapy development under socially sustainable conditions. Within Europe, we participate in the European Rare Diseases Research Alliance (ERDERA), which aims to accelerate patient access to therapies by enhancing international collaboration, exchange of knowledge and data, and alignment of research and innovation activities.

Learning communities

Drug repurposing

One of the cost-efficient options for development of pharmaceutical treatments for rare diseases is the re-use of existing medication for other clinical applications, drug repurposing. This prevents a large part of the development costs of (small molecule) drugs as is traditionally done for common diseases. There is considerable experience in house on preclinical therapy development for rare diseases, both with traditional drug (or nutrition)-based interventions as innovative therapies (antisense, gene and cell therapy). Yet, the road to the clinic is difficult to oversee for preclinical researchers, expertise with these trajectories is fragmented, and preclinical researchers often reinvent the wheel.

To solve the identified gap of fragmented availability of expertise, we propose to establish a learning community in which clinicians, researchers and support staff are brought together, strongly integrated with ancillary expertise in supportive departments on trials, valorization, regulations, approval, drug access protocols, etc. This will facilitate exchange of experiences and easy access to standardized protocols and support.

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Advanced in vitro models

More information about this specific topic will follow soon.