SHIELD-Fabry
Project data
Project financing: 13 930 904,32 PLN (including financing for UMED: 10 026 097,22 PLN), financed by the Medical Research Agency (ABM) - ABM/2024/1.
Project description:
SHIELD-Fabry is a prospective randomized crossover study, investigating the effect of minimal doses of corticosteroids as an adjunctive treatment to enzyme replacement therapy in Fabry disease with cardiac involvement. Study subjects will be recruited from patients – diagnosed with FD with cardiac involvement, on ERT or chaperone therapy. The ultimate number of study participants is estimated to be at the level of 40 subjects. This number seems to be adequate, given the eligibility of patients already diagnosed with FD. Additionally, The Association of Families with Fabry Disease will provide reliable access to the patient community and therefore streamline recruitment of potential study participants.
Fabry Disease (FD) represents a genetic disorder inherited in an X-chromosome-coupled recessive manner, linked to the Xq22 region. Mutation of the GLA gene leads to a severe deficiency or complete absence of activity of the α-galactosidase A (α-Gal A) enzyme, which catalyses the hydrolysis of globotriaosylceramide (Gb-3), cleaving the terminal galactose residue from the molecule. The enzymatic deficiency casuses a progressive accumulation of glycolipids – globotriaosylceramide and its deacylated form, globotriaosylphosphingosine (lyso-Gb-3) – in the plasma and in various cells of the body, leading to damage in those cells and significant disruption of their normal function. The resulting lesions mainly involve podocytes, cardiomyocytes, endothelial cells, vascular musculature, and nerve fibres. Due to the heterogeneity of organs affected, symptoms are often very vague, making diagnosis and therapy very challenging.
Given the observable clinical symptoms, natural history of multi-organ dysfunction, and the emphasis on the key role of inflammatory pathogenesis in FD, these all provide a strong rationale to target the inflammation component of the disease pathway, or at least seek adjunctive therapies to address this area in Fabry patients. This may not only prolong life, but also significantly improve its quality, which seems to be the key outcome of the chronic care in this group of patients.
- Beneficiary
Medical University of Lodz (Leader)
The Central Teaching Hospital of the Medical University of Lodz (Partner)
The Association of Families with Fabry Disease (Partner)
- Coordinating Principal Investigator
Krzysztof Kaczmarek, MD, PhD