Use of sterculic acid to treat choroidal neovascularization
Sterculic acid is a naturally occurring fatty acid found in the seeds of several plants. NEI investigators have recently discovered that sterculic acid is a potent inhibitor of oxidized lipid-mediated inflammation both in vitro and in vivo. Sterculic acid has potent anti-angiogenic activity and daily drops can inhibit choroidal neovascularization in the retina of laser treated rats.
The present invention is directed to methods of using sterculic acid for the treatment of inflammation; in particular, 7-ketocholesterol (7KCh) mediated inflammation, neural cytotoxicity and angiogenesis. 7KCh is a potent VEGF inducer and sterculic acid can completely ablate this induction. Diseases suspected of being mediated by 7KCh-induced inflammation/cytotoxicity include atherosclerosis, age-related macular degeneration, and Alzheimer’s disease. Diseases mediated by unregulated angiogenesis include certain cancers and age-related macular degeneration. Also disclosed are methods of treating atherosclerosis or Alzheimer’s disease using sterculic acid.
Inventors
Ignacio R. Rodriguez, Ph.D., National Eye Institute
William Samuel, Ph.D., National Eye Institute
Development Status
In vitro and animal model data have been collected, a patent application has been filed. This technology is appropriate for further development through a CRADA or license.
DHHS Reference No. E-092-2010
Licensing Contact
Sury Vepa, Ph.D., J.D.
Office of Technology Transfer
National Institutes of Health
Nitisinone for treatment of oculocutaneous/ocular albinism and for increasing pigmentation
Oculocutaneous albinism (OCA) is a congenital disorder characterized by the complete or partial absence of pigment in the eyes, skin and hair. In ocular albinism, only the eyes lack pigment. Patients with albinism experience varying degrees of vision loss primarily due to factors affecting visual pathway development. The most common form of OCA in North America (OCA1) is due to defects in tyrosinase, the rate-limiting step in pigment production. Patients with type OCA1a albinism show no measurable tyrosinase activity while type OCA1b albinism patients have greatly diminished tyrosinase activity.
Nitisinone (NTBC) is an FDA-approved drug used in the treatment of tyrosinemia, type 1 by blocking the normal degradation pathway of tyrosine thus allowing greater circulating plasma levels of tyrosine. NEI has found that administration of NTBC can result in increased circulating tyrosine levels, an increase in tyrosinase activity, and subsequently, increased pigmentation in an experimental animal model of OCA. Thus, NTBC administration may represent a useful method for treating some forms of albinism.
Inventors
Brian P. Brooks, M.D., National Eye Institute
William A. Gahl, M.D., Ph.D., National Human Genome Research Institute
David R. Adams, M.D., Ph.D., National Human Genome Research Institute
Development Status
Data has been collected in animal models, a patent application has been filed, pilot clinical studies as a therapeutic may be appropriate at this time. This technology is appropriate for further development under a CRADA or license.
DHHS Reference No. E-113-2010
Licensing Contact
Sury Vepa, Ph.D., J.D.
Office of Technology Transfer
National Institutes of Health
Methods for using interferon gamma to absorb fluid from the subretinal space
The accumulation of subretinal fluid is associated with certain adverse ocular conditions, including chronic macular edema, age-related macular degeneration, diabetic retinopathy, or retinal injury, and may be associated with abnormal retinal pigmented epithelium (RPE) cell proliferation and migration, and inflammatory, dystrophic diseases of the retina and choroid.
NEI is developing methods by which interferon-gamma (IFN-gamma) can be used to remove subretinal fluid through external application or subretinal injection. Claims in the pending patent application are directed to methods for treating decreases in visual acuity associated with diseases that cause subretinal fluid to accumulate. Additional claims are directed at methods for treating age-related macular degeneration, macular edema, retinopathy, retinal detachment, or glaucoma, which involve decreasing the amount of fluid present in the subretinal space.
Applications
This technology can be used to treat decreases in visual acuity associated with accumulation of fluid in the subretinal space due to disease or injury.
Inventors
Rong Li, Ph.D., National Eye Institute
Sheldon S. Miller, Ph.D., National Eye Institute
Arvydas Maminishkis, Ph.D., National Eye Institute
Development status
Preclinical and animal model studies in progress. Patent applications filed.
DHHS Reference No. E-169-2008
Licensing Contact
Sury Vepa, Ph.D., J.D.
Office of Technology Transfer
National Institutes of Health
Treatment and prevention of age-related macular degeneration and other eye-related diseases with miRNAs
Small, noncoding RNAs or microRNAs (miRNAs) regulate gene expression by repressing translation and degrading messengerRNA. miRNAs are involved in many critical biological processes and are implicated in the development of the eye. The retinal pigmented epithelium (RPE) plays a significant role in regulating the environment around the photoreceptors in the distal retina. Expression profiling of miRNA in RPE and the adjacent retina and choroid has identified six highly expressed miRNAs within RPE cells. Further experiments indicate that miRNA 204 and miRNA 211 play a critical role in the control of transepithelial electrical resistance.
NEI is developing uses for anti-miRNAs or miRNA mimics directed against miRNA 204 and miRNA 211 to prevent epithelial cell differentiation, proliferation, and migration. Therapeutic use of anti-miRNA 204 or antimiRNA 211 may be applicable to treating ocular diseases including age-related macular degeneration, proliferative vitreal retinopathy, and neovascular diseases.
Inventors
Fei Wang, Ph.D.
Sheldon S. Miller, Ph.D., National Eye Institute
Development Status
Knockout mouse experiments are in progress, patent applications are filed, efficacy testing in neovascular eye disease models is planned.
DHHS reference No. E-056-2008
Licensing Contact
Sury Vepa, Ph.D., J.D.
Office of Technology Transfer
National Institutes of Health
PEDF related studies
Second-Generation PEDF Related Peptides Pigment epithelium-derived factor (PEDF) is a protein in the serpin superfamily, which has neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. PEDF levels in the human eye change with aging, retinopathic diseases such as AMD and diabetic retinopathy, and certain cancers.
The NEI Laboratory of Retinal Cell and Molecular Biology (LRCMB) is interested in developing secondgeneration peptides that express the individual biological properties of the multifunctional PEDF. PEDF-Receptor Agonists and Antagonists PEDF-R is a phospholipase-linked membrane protein, which acts as a high-affinity PEDF receptor. PEDF binding stimulates phospholipase activity, suggesting a molecular pathway by which the cell surface ligand:receptor interaction could generate a lipid mediated cell signal.
LRCMB is interested in developing agonists and antagonists of PEDF ligand:receptor interactions, or designing and testing materials that interfere with or stimulate a single activity of PEDF. Because PEDF acts as a multifunctional regulatory protein of the eye, these projects have the potential to generate diagnostic or therapeutic materials related to ocular diseases triggered by pathological neovascularization, retinal degenerations, and tumors.
Senior Investigator
S. Patricia Becerra, Ph.D., National Eye Institute
DHHS Reference No. E-185-1992
Technology Specialist
Alan E. Hubbs, Ph.D.
Office of Technology Transfer
National Institutes of Health