title: Gene and protein therapies utilizing VEGF for ALS.
abstract: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is usually fatal within 2-5years. Unfortunately, the only treatment currently available is riluzole, which has a limited efficacy. As a redress, there is an expanding literature focusing on other potential treatments. One such potential treatment option utilizes the vascular endothelial growth factor (VEGF) family, which includes factors that are primarily associated with angiogenesis but are now increasingly recognized to have neurotrophic effects. Reduced expression of a member of this family, VEGF-A, in mice results in neurodegeneration similar to that of ALS, while treatment of animal models of ALS with either VEGF-A gene therapy or VEGF-A protein has yielded positive therapeutic outcomes. These basic research findings raise the potential for a VEGF therapy to be translated to the clinic for the treatment of ALS. This review covers the VEGF family, its receptors and neurotrophic effects as well as VEGF therapy in animal models of ALS and advances towards clinical trials.
authors.affiliation: Department of Neurosurgery, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, United States.
authors.forename: Orion P
authors.initials: OP
authors.lastname: Keifer
authors.affiliation: Department of Neurosurgery, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, United States.
authors.forename: Deirdre M
authors.initials: DM
authors.lastname: O'Connor
authors.affiliation: Department of Neurosurgery, Emory University, 101 Woodruff Circle, Atlanta, GA 30322, United States. Electronic address: nboulis@emory.edu.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Boulis
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015195:Drug Design; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D011506:Proteins / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D011506:Proteins; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: AAV; ALS; CNS; Clinical trials; FIG4; FTD; FUS; Gene therapy; HRE; ICV; IGF-1; NFκB; NRP; PlGF; Protein therapy; SETX; SOD1; TAR DNA-binding domain protein; TDP43; UBQLN2; UTR; VEGF; VEGFR; adeno-associated virus; amyotrophic lateral sclerosis; central nervous system; frontotemporal dementia; fused in sarcoma; hypoxia response element; insulin-like growth factor 1; intracerebroventricular; neuropilin; nuclear factor kappa-light-chain-enhancer of activated B cells; placental growth factor; polyphosphoinositide phosphatase; senataxin; superoxide dismutase 1; ubiquitin-like protein ubiquilin 2; untranslated region; vascular endothelia growth factor receptor; vascular endothelial growth factor