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The first dialyzer performs traditional diffusion dialysis and ultrafiltration to maintain pH, fluid and electrolyte balance. The second dialyzer is the site of oxygen delivery. Pressure in both limbs of the circuit is monitored during the circulation procedure.
Source publication
Over the past decade much progress has been made towards the treatment of disease with recombinant adeno-associated viral vectors, ranging from cancer to muscular dystrophies, and autoimmune diseases to cystic fibrosis. Given inherent challenges of vector delivery we developed a system incorporating commercially available dialysis equipment. This c...
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Purpose
Vietnam is estimated to have approximately 30,000 hemophilia B (HB) carriers, with hundreds of new cases registered annually. However, comprehensive molecular studies on HB remain limited. Therefore, this study aimed to characterize genetic variants and assess their clinical significance in unrelated Vietnamese patients with HB.
Patients a...
Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B...
Introduction:
Muscle hematomas are the second most common complication of hemophilia and insufficient treatment may result in serious and even life-threatening complications. Hemophilic dogs and rats do experience spontaneous muscle bleeding, but currently, no experimental animal model is available specifically investigating spontaneous muscle ble...
Aims
Gene therapy trials aim to provide a functional cure for patients with haemophilia B (HB), and treatment impact is analyzed by factor IX expression levels (FELs). We investigated the relationship of FELs with health-related quality of life (HRQoL) and costs.
Materials and methods
This was a retrospective cross-sectional analysis of the Europe...
Recombinant factor IX Fc fusion protein (rFIXFc) is a recombinant coagulation factor composed of a single molecule of recombinant factor IX (rFIX) covalently fused to the Fc domain of human immunoglobulin G1 (IgG1) with no intervening sequence. An extensive nonclinical program was performed to support the clinical development of rFIXFc for treatmen...
Citations
... Bilirubin and Albumin measurement protocols were the same as in previous work [23]. Hollow fiber inner radius (µm) 100 [57] 100 [58] Hollow fiber outer radius (µm) 140 [57] 140 [59] Hollow fiber length (cm) 21 [60] 20 [58] Area (m 2 ) 1.3 [57] 0.4 [58] Housing inner radius (mm) 20 [57] 11 (measured) ...
Liver failure is the 12th leading cause of death worldwide. Protein-bound toxins such as bilirubin are responsible for many complications of the disease. Binder dialysis systems use albumin or another binding molecule in dialysate and detoxifying sorbent columns to remove these toxins. Systems like the molecular adsorbent recirculating system and BioLogic-DT have existed since the 1990s, but survival benefits in randomized controlled trials have not been consistent. New binder dialysis systems, including open albumin dialysis and the Advanced Multi-Organ Replacement system, are being developed. Optimal conditions for binder dialysis have not been established. We developed and validated a computational model of bound solute dialysis. It predicted the impact of changing between two test setups using different polysulfone dialyzers (F3 and F6HPS). We then predicted the impact of varying the dialysate flow rate on toxin removal. We found that bilirubin removal declines with dialysate flow rate. This can be explained through a linear decline in free bilirubin membrane permeability. Our model quantifies this decline through a single parameter (polysulfone dialyzers). Validation for additional dialyzers and flow rates will be needed. This model will benefit clinical trials by predicting optimal dialyzer and flow rate conditions. Accounting for toxin adsorption onto the dialyzer membrane may improve results further.
Liver failure is the 12th leading cause of death worldwide. Protein bound toxins such as bilirubin are responsible for many complications of the disease. Binder dialysis systems use albumin dialysate and detoxifying sorbent columns to remove these toxins. Systems like the Molecular Adsorbent Recirculating System (MARS) and BioLogic-DT have existed since the 1990s, but survival benefit in randomized controlled trials have not been consistent. Thus, a new generation of binder dialysis systems, including Open Albumin Dialysis (OPAL) and the Advanced Multi-Organ Replacement System (AMOR) are being developed. Optimal conditions for binder dialysis have not been established. We developed and validated a computational model of bound solute dialysis using established thermodynamic theories. Our objective is to improve AMOR therapy. We confirmed our model's validity by predicting the impact of changing between two benchtop dialysis setups using different polysulfone dialyzers (F3 and F6HPS). We then applied it to predict the impact of varying dialysate flow rate on toxin removal. We found that bilirubin removal is independent of dialysate flow rate within the clinically relevant range (20 mL/min - 800 mL/min), matching our model's predictions. At very low dialysate flow rates (2 mL/min), bilirubin removal declines, deviating from the thermodynamic model. This model may be useful to achieving optimal clinical outcomes by setting optimal dialyzer and flow rate conditions. Further improvement is possible by accounting for toxin adsorption onto the dialyzer membrane.
Duchenne muscular dystrophy (DMD) is a fatal, X-linked disease caused by mutations in the massive dystrophin gene that lead to extremely low or non-detectable levels of dystrophin. Conversely, Becker muscular dystrophy (BMD) is a highly variable and significantly less severe disease that results from truncated or poorly expressed dystrophin variants. Based on the insights from BMD patient mutations and knowledge of the working domains of dystrophin, various miniaturized mini- and micro-dystrophin constructs have been developed for gene therapy and tested in preclinical animal models. Much of the central rod domain can be deleted with minimal loss of function, provided that spectrin-like repeats 16 and 17, which contain the neuronal nitric oxide synthase localization domain, are maintained. The N-terminal actin-binding domain and the C-terminal dystroglycan-binding domain (covering parts of “hinge 4” and the cysteine-rich domain) provide important functions and stability, while the function of the C-terminal domain appears redundant. While a range of viral vectors expressing these miniaturized genes have been utilized for DMD gene therapy, the recent focus has been on recombinant adeno-associated viral vectors (rAAV), which have now been tested extensively in mdx mouse and DMD dog models, and have own entered clinical trials. These vectors have shown significant improvement in the DMD pathology of mice and dogs, although complete correction has yet to be attained. Gene editing through exon-skipping oligonucleotides and CRISPR/Cas9 is also being developed, with varying success and a sense that both technologies are still in their infancy. While promising rAAV clinical trials have begun, there is still work to be done to advance the field of gene replacement for DMD.
