MyVisionTest News Archive
Oct 11, 2008
Anti-S1P Treatment Inhibits Choroidal Neovascularization In Mice
Sphingosine-1-phosphate (S1P) is a bioactive lipid that promotes cell proliferation, migration, and protection from cell death (apoptosis). In pathological conditions, S1P has many actions that can promote inflammation, pathogenic fibrosis, and dysregulated angiogenesis.
Lpath Inc. has produced a monoclonal anti-S1P antibody (Sphingomab) directed against S1P. We hypothesize that this antibody could be used as a therapeutic molecular sponge to selectively absorb S1P, thus lowering the effective extracellular concentrations of S1P.
Growing evidence suggests that S1P could contribute to both the early and the late stages of exudative (or "wet") AMD. S1P has a pronounced non-VEGF dependent pro-angiogenic effect. S1P also stimulates migration, proliferation and survival of multiple cell types, including fibroblasts and endothelial and inflammatory cells. S1P is also linked to the production and activation of VEGF, FGF, PDGF, MCP-1, IL-6, IL-8 and other growth factors implicated in the pathogenesis of exudative AMD. Inhibiting the action of S1P could therefore be an effective therapeutic treatment for exudative AMD that may offer significant advantages over exclusively anti-VEGF approaches or act synergistically with them to address the complex processes and multiple steps that ultimately lead to AMD associated visual loss.
Recently, two papers showing the role of S1P in ocular disorders have been published. The papers present data that Lpath's therapeutic anti-S1P antibody, iSONEP, can mitigate not only choroidal neovascular (CNV) lesions but also fibrotic lesions in a standard animal model of human exudative AMD.
The results were published in the journal Experimental Eye Research.
The first paper shows how iSONEP almost completely mitigated the CNV lesions produced by laser-induced choroidal damage in a mouse model that mimics the pathologic neovascularization experienced by patients with wet AMD. Both the mouse form and the humanized form of the anti-S1P antibody were effective in nearly eliminating the lesions.
The paper also revealed subretinal fibrosis (scarring) was reduced in the lesions. This ability of iSONEP to mitigate scarring was consistent with a second paper which presents how S1P, the molecular target of iSONEP, not only was produced by ocular cells, but in fact acted on those cells to promote fibrotic responses responsible for scarring.
"This is the first published paper demonstrating that S1P is a mediator of CNV in an AMD model," said Glenn Stoller, head of Lpath's Ocular Division. "The results illustrate that antibody-mediated inhibition of S1P may be highly effective in preventing abnormal blood vessel growth and fibrosis beneath the retina."
Scott Pancoast, Lpath's president and CEO, added, "Inhibition of S1P is a novel approach to treating AMD, and it provides additional mechanisms of action as compared with anti-VEGF drugs."
Lpath has received approval from the FDA to commence a Phase 1 clinical trial with iSONEP in wet AMD patients, which is scheduled to begin soon.
Read more...
Exp Eye Res. 2008 Aug 6. [Epub ahead of print]
Tags: wet AMD, S1P
Sphingosine-1-phosphate (S1P) is a bioactive lipid that promotes cell proliferation, migration, and protection from cell death (apoptosis). In pathological conditions, S1P has many actions that can promote inflammation, pathogenic fibrosis, and dysregulated angiogenesis. Lpath Inc. has produced a monoclonal anti-S1P antibody (Sphingomab) directed against S1P. We hypothesize that this antibody could be used as a therapeutic molecular sponge to selectively absorb S1P, thus lowering the effective extracellular concentrations of S1P.
Recently, two papers showing the role of S1P in ocular disorders have been published. The papers present data that Lpath's therapeutic anti-S1P antibody, iSONEP, can mitigate not only choroidal neovascular (CNV) lesions but also fibrotic lesions in a standard animal model of human exudative AMD.
The results were published in the journal Experimental Eye Research.
The first paper shows how iSONEP almost completely mitigated the CNV lesions produced by laser-induced choroidal damage in a mouse model that mimics the pathologic neovascularization experienced by patients with wet AMD. Both the mouse form and the humanized form of the anti-S1P antibody were effective in nearly eliminating the lesions.
The paper also revealed subretinal fibrosis (scarring) was reduced in the lesions. This ability of iSONEP to mitigate scarring was consistent with a second paper which presents how S1P, the molecular target of iSONEP, not only was produced by ocular cells, but in fact acted on those cells to promote fibrotic responses responsible for scarring.
"This is the first published paper demonstrating that S1P is a mediator of CNV in an AMD model," said Glenn Stoller, head of Lpath's Ocular Division. "The results illustrate that antibody-mediated inhibition of S1P may be highly effective in preventing abnormal blood vessel growth and fibrosis beneath the retina."
Scott Pancoast, Lpath's president and CEO, added, "Inhibition of S1P is a novel approach to treating AMD, and it provides additional mechanisms of action as compared with anti-VEGF drugs."
Lpath has received approval from the FDA to commence a Phase 1 clinical trial with iSONEP in wet AMD patients, which is scheduled to begin soon.
Read more...
Exp Eye Res. 2008 Aug 6. [Epub ahead of print]
