Anderson-Fabry Disease (AFD)
Anderson-Fabry disease (AFD) is a condition affecting the X chromosome characterized by the underactive enzyme alpha-galactosidase and classified as a lysosomal storage disorder. Although AFD is considered a progressive disease affecting multiple body systems, one of its major complications is infiltrative cardiomyopathy with a range of cardiovascular symptoms. Protheragen is a research service provider to accelerate the drug discovery and development drought for rare cardiovascular diseases like AFD.
Overview of Anderson-Fabry Disease (AFD)
Anderson-Fabry disease (AFD) is classified as a rare X-linked inherited lysosomal storage disorder that stems from either complete or partial absence of alfa-galactosidase A enzymatic activity in lysosomes, leading to glycosphingolipid deposits in different tissues. It mainly affects the heart which often presents as left ventricular hypertrophy and may progress to cardiac fibrosis, heart failure, valvular disease, cardiac arrhythmias, and sudden cardiac death. The global prevalence of individuals with AFD is approximately 1 in 40,000 to 1 in 170,000 live births.
Fig.1 Imaging findings and "red flags" of AFD cardiomyopathy. (Fuertes Kenneally, L., et al., 2022)Pathogenesis of Anderson-Fabry Disease (AFD)
Anderson-Fabry disease (AFD) results from mutations in the GLA gene at the locus Xq22 on the X chromosome. These mutations lead to deficiency or total lack of the α-galactosidase enzyme, causing an excess of globotriaosylceramide (Gb3) which is sent to the lysosomes in many tissues such as the heart, kidneys, skin, and vascular endothelium. Gb3 infiltration into the heart may cause left ventricular hypertrophy (LVH), valvular disease, systolic and diastolic dysfunctions as well as conduction system diseases.
Fig.2 Pathophysiology and therapy options for AFD. (Averbuch, T., et al., 2023)Therapeutics Development for Anderson-Fabry Disease (AFD)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Migalastat | Accomplishing the activation of the enzyme (α-Gal) and enhancing its catabolic activity. | α-Gal A | NCT06904261 | Phase III |
| PRX-102 | It functions by enzymatically breaking down glycosphingolipid accumulations, specifically targeting Gb3. | GL3 | NCT05710692 | Phase II/III |
| HM15421 | Binds selectively to the misfolded enzyme in the endoplasmic reticulum, stabilizing its conformation. | α-Gal A | NCT06858397 | Phase I/II |
| EXG110 | Transduces a functional GLA gene to individual cells via a viral vector. | GLA | NCT06819514 | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen's commitment to every service we offer precision and excellence makes certain that our partners are able to effectively perform the drug development and, in the end, deliver transformative therapies. Our multidisciplinary team tailor solutions for complex disease challenges using their vast knowledge in diagnostics, therapeutics, and disease models.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for AFD
Using cutting-edge genetic manipulation technologies, our company offers tailored AFD animal model construction services and guarantees that optimized AFD animal models fulfill bespoke research requirements, enabling thorough exploration of the pathology and the assessment of innovative therapy methods.
Genetically Engineered Animal Model
Genetically Engineered animal models for AFD are created by inducing mutations in the GLA gene, enabling thorough in vivo exploration of disease mechanisms and therapeutic interventions.
Optional models:
- GLA knockout mouse model
- TgG3S/GLA knockout mouse model
- Other models
- TgG3S mouse model
- GLA knockout rat model
Alongside our primary research offerings, Protheragen serves a full range of preclinical support which encompasses pharmacokinetic examinations as well as safety evaluations for drugs. Our team employs advanced technologies and sound techniques to verify that each candidate compound survives multilevel safety and efficacy evaluations. For further details, kindly reach us if you are interested in our services.
References
- Fuertes Kenneally, Laura et al. "Fabry Disease Cardiomyopathy: A Review of the Role of Cardiac Imaging from Diagnosis to Treatment." Reviews in cardiovascular medicine 23.6 (2022): 192.
- Averbuch, Tauben et al. "Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies." Frontiers in cardiovascular medicine 10 (2023): 1152568.
For research use only, not for clinical use.