Search Results (7)

Diabetic retinopathy (DR) is one of the leading causes of preventable blindness worldwide. It is characterized by a spectrum of disease that spans mild non-proliferative diabetic retinopathy (NPDR) all the way to neovascular glaucoma and tractional retinal detachment secondary to proliferative diabetic retinopathy (PDR). Most eyes with DR remain asymptomatic unless vision-threatening complications, such as diabetic macular edema (DME) and/or PDR, develop. Current treatment options include laser photocoagulation and/or anti-VEGF intravitreal injections. Patients under treatment with anti-VEGF agents usually require constant monitoring and multiple injections to optimize outcomes. This treatment burden plays a key role in suboptimal adherence to treatment in many patients, compromising their outcomes. Gene therapy has emerged as a promising therapeutic option for DR. The mechanism for current trials evaluating gene therapies for DR consists of delivering transgenes to the retina that express anti-angiogenic proteins that inhibit VEGF. Preliminary results from the SPECTRA (4D-150) and ALTITUDE (ABBV-RGX-314) studies are promising, demonstrating an improvement in the diabetic retinopathy severity score and a reduction in the treatment burden. In contrast, the INFINITY (ADVM-022) trial was complicated by several cases of severe inflammation and hypotony that led the sponsor to discontinue further development of this product for DME. Full article

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases. Full article

Age-related skeletal muscle atrophy and weakness not only reduce the quality of life of those afflicted, but also worsen the prognosis of underlying diseases. We evaluated the effect of RGX365, a protopanaxatriol-type rare ginsenoside mixture, on improving skeletal muscle atrophy. We investigated the myogenic effect of RGX365 on mouse myoblast cells (C2C12) and dexamethasone (10 µM)-induced atrophy of differentiated C2C12. RGX365-treated myotube diameters and myosin heavy chain (MyHC) expression levels were analyzed using immunofluorescence. We evaluated the myogenic effects of RGX365 in aging sarcopenic mice. RGX365 increased myoblast differentiation and MyHC expression, and attenuated the muscle atrophy-inducing F-box (Atrogin-1) and muscle RING finger 1 (MuRF1) expression. Notably, one month of oral administration of RGX365 to 23-month-old sarcopenic mice improved muscle fiber size and the expression of skeletal muscle regeneration-associated molecules. In conclusion, rare ginsenosides, agonists of steroid receptors, can ameliorate skeletal muscle atrophy during long-term administration. Full article

The controlled release of antibiotics prevents the spread of pathogens and thereby improves healing processes in regenerative medicine. However, high concentrations may interfere with healing processes. It is therefore advantageous to use biodegradable materials for a controlled release. In particular, multilayer materials enable differential release at different surfaces. For this purpose, collagen sheets of different properties can be bonded by photochemical crosslinking. Here, we present the development and application of an easily accessible, additively manufactured sample holder to study the controlled release of vancomycin from modularly assembled collagen laminates in two directions. As proof-of-concept, we show that laminates of collagen sheets covalently linked by rose bengal and green light crosslinking (RGX) can be tightly inserted into the device without leakage from the upper to lower cavity. We used this sample holder to detect the release of vancomycin from symmetrically and asymmetrically loaded two-layer and three-layer collagen laminates into the upper and lower cavity of the sample holder. We show that these collagen laminates are characterized by a collagen type-dependent vancomycin release, enabling the control of antibiotic release profiles as well as the direction of antibiotic release. Full article

Suprachoroidal drug delivery technology has advanced rapidly and emerged as a promising administration route for a variety of therapeutic candidates, in order to target multiple ocular diseases, ranging from neovascular age-related macular degeneration to choroidal melanoma. This review summarizes the latest preclinical and clinical progress in suprachoroidal delivery of therapeutic agents, including small molecule suspensions, polymeric entrapped small molecules, gene therapy (viral and nonviral nanoparticles), viral nanoparticle conjugates (VNCs), and cell therapy. Formulation customization is critical in achieving favorable pharmacokinetics, and sustained drug release profiles have been repeatedly observed for multiple small molecule suspensions and polymeric formulations. Novel therapeutic agents such as viral and nonviral gene therapy, as well as VNCs, have demonstrated promise in animal studies. Several of these suprachoroidally-administered therapies have been assessed in clinical trials, including small molecule suspensions of triamcinolone acetonide and axitinib, viral vector RGX-314 for gene therapy, and VNC AU-011. With continued drug delivery research and optimization, coupled with customized drug formulations, suprachoroidal drug delivery may address large unmet therapeutic needs in ophthalmology, targeting affected tissues with novel therapies for efficacy benefits, compartmentalizing therapies away from unaffected tissues for safety benefits, and achieving durability to relieve the treatment burden noted with current agents. Full article

For medical application, easily accessible biomaterials with tailored properties are desirable. Collagen type I represents a biomaterial of choice for regenerative medicine and tissue engineering. Here, we present a simple method to modify the properties of collagen and to generate collagen laminates. We selected three commercially available collagen sheets with different thicknesses and densities and examined the effect of rose bengal and green light collagen crosslinking (RGX) on properties such as microstructure, swelling degree, mechanical stability, cell compatibility and drug release. The highest impact of RGX was measured for Atelocollagen, for which the swelling degree was reduced from 630% (w/w) to 520% (w/w) and thickness measured under force application increased from 0.014 mm to 0.455 mm, indicating a significant increase in mechanical stability. Microstructural analysis revealed that the sponge-like structure was replaced by a fibrous structure. While the initial burst effect during vancomycin release was not influenced by crosslinking, RGX increased cell proliferation on sheets of Atelocollagen and on Collagen Solutions. We furthermore demonstrate that RGX can be used to covalently attach different sheets to create materials with combined properties, making the modification and combination of readily available sheets with RGX an attractive approach for clinical application. Full article