# US 10,501,798 B2 · Method and kit for prognosis of OPA1 gene induced diseases, E.G. Kjers optic atrophy

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- Number: US 10,501,798 B2
- Document ID: US10501798B2
- Status: Granted
- Kind: B2
- Application number: 15/129,020
- Filed: 2015-03-27
- Published: 2017-04-13
- Granted: 2019-12-10
- Earliest claimed: 2014-03-27
- Assignees: Universite Toulouse III - Paul Sabatier; Centre National De La Recherche Scientifique
- Applicants: Universite Toulouse III-Paul Sabatier; Centre National De La Recherche Scientifique
- Inventors: Noelie Davezac; Pascale Belenguer; Aurelie Millet
- Web page: https://patentgrep.com/patent/US10501798B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/573: for enzymes or isoenzymes
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/16: Ophthalmology
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Providing Nuclear factor (erythroid-derived 2)-like 2 (NRF2)-activated genes products, e.g. SOD1 and CAT, in their use in the prognosis of an OPA1 gene- or OPA1 gene product-deficit-induced disease, or related complications, e.g. optic atrophy and optic neuropathy, in a biological sample selected from fibroblasts, epithelial cells, blood samples or a mixture thereof, of a patient affected or suspected to be affected by the disease.

## Claims

### Claim 1

A method for the in vitro diagnosis and treatment of OPA1-deficit induced autosomal dominant optic atrophy (DOA, OMIM# 165500) and/or a complication associated with OPA1-deficit induced DOA selected from “DOA plus” syndrome disorders in a subject, comprising
measuring in a biological sample selected from the group consisting of fibroblasts, epithelial cells, blood samples and mixtures thereof, of said subject, expression and/or activity of a Nuclear Factor (erythroid-derived 2)-like 2 (NRF2)-activated gene product selected from the group consisting of NRF2, SOD1, SOD2, catalase, GSTP1, NQO1, Glutathione Reductase, Peroxiredoxin 1, Hemeoxigenase 1, Thioredoxin reductase 1, and Glutamate Cystein Ligase,
comparing said expression and/or activity measured in said biological sample of said subject to that of a measured expression and/or activity of a same NRF2-activated gene product in a biological sample selected from the group consisting of fibroblasts, epithelial cells, blood samples and a mixture thereof taken from a control subject,
determining that said expression and/or activity measured in said biological sample from said subject is lower than said measured expression and/or activity in said biological sample from said control subject, and concluding said subject as suffering from said OPA1-deficit induced DOA and/or said complication associated with OPA1-deficit induced DOA,
administering to said subject suffering from said OPA1-deficit induced DOA and/or said complication associated with OPA1-deficit induced DOA a treatment comprising administering at least one compound selected from the group consisting of Glutathione, Vitamin A, Vitamin C, Vitamin E, Coenzyme Q10 and Coenzyme Q10 analogs, Manganese, Iodide, Carotenoid terpenoids, Natural phenols, Phenolic acids and their esters, nonflavonoid phenolics, organic antioxidants selected from the group consisting of Capsaicin, Bilirubin, oxalic acid, phytic acid, N-Acetylcysteine, R-α-Lipoic acid, and fat and water soluble Uric acid, ARE inducers selected from the Sulforafane, Nordihydroguaiaretic acid, Diallyl Sulfid, Diallyl disulfid, Diallyl trisulfid, Pterostilbene, 1,2-dithiole-3-thione (D3T), 5,6-dihydro-cyclopento-(c)-1,2-dithiole-(4H)-thione (CPDT), Oltipraz, Salicylcurcuminoids, BG12, and Bardoxolonemethyl, and combinations thereof.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said “DOA plus” syndrome disorders are selected from the group consisting of external ophthalmoplegia, ataxia, deafness, glaucoma, Primary Open Angle Glaucoma, myopathy, peripheral neuropathy, and neurodegenerative diseases related to the age.

### Claim 3 (depends on 1)

The method according to claim 1, wherein said control subject is one of:
(i) a healthy subject not suffering from said OPA1-deficit induced DOA and/or said complication associated with OPA1-deficit induced DOA and having the same age as said subject, or
(ii) said subject for whom said expression and/or activity has been previously measured.

### Claim 4 (depends on 3)

The method according to claim 3 wherein said control subject is said subject for whom said expression and/or activity has been previously measured the said previous measure being performed at birth of said subject.

### Claim 5 (depends on 1)

The in vitro method according to claim 1 wherein the biological sample of said subject is not an invasive sample obtained from a retina or an optic nerve.