Exudative

AMD, also termed neovascular AMD, is caused by proliferation of choroidal neovascularization (CNV), leading to bleeding and loss of photoreceptors through fibrovascular scarring. CNV and related manifestations (subretinal hemorrhage, detachment of the retinal pigment epithelium, and fibrovascular disciform scarring) are click here the most common causes of severe vision loss resulting from AMD.5 Untreated, exudative AMD can lead to progressive and substantial loss of central vision and a reduction in quality of life. The relationship between vascular endothelial growth factor-A (VEGF-A) and AMD pathogenesis has led to the development of anti-VEGF therapies that inhibit CNV leakage and reduce vessel permeability.6 Several VEGF antagonists have been developed, including monoclonal antibodies (ranibizumab and bevacizumab); receptor fragments (aflibercept); and other molecules (pegaptanib, a DNA aptamer).7, 8, 9, 10, 11, 12 and 13 These agents have radically altered the management of neovascular AMD and have become the current standard of care. Anti-VEGF agents are

injected directly into the vitreous cavity. Although treatment has evolved from monthly dosing to individualized regimens, the best results are achieved with GSK1120212 chemical structure injections every 4–8 weeks in order to maintain improvement in central vision, placing a considerable burden of treatment on patients, physicians and healthcare systems.7 and 14 MP0112 is a recombinant protein of the designed ankyrin repeat protein (DARPin) family. DARPins are small, single-domain proteins that can selectively bind to a target protein with high affinity and specificity.15 These genetically engineered antibody-mimetic proteins show greater stability and at least equal affinity

with immunoglobulins, making them effective investigational and therapeutic tools.16 The in vitro and in vivo effectiveness has been demonstrated in areas that MycoClean Mycoplasma Removal Kit include preclinical tumor targeting and diagnostics.17, 18, 19, 20, 21 and 22 In vitro, MP0112 has been shown to act as a highly potent antagonist to all VEGF-A isoforms (KD of 1–4 pM; data on file; Molecular Partners, Zurich-Schlieren, Switzerland). Animal studies have demonstrated the high efficacy of MP0112 to inhibit abnormal neovascularization (data on file, Molecular Partners). In a rabbit model of ocular pharmacokinetics with vascular leakage inhibition as read-out, MP0112 was fully active for at least 30 days, whereas ranibizumab did not show activity after 30 days due to faster clearance (data on file, Molecular Partners). Good laboratory-practice toxicology studies were performed and revealed that inflammation can result from potential toxicity in patients (data on file, Molecular Partners).