IP Library Granted Patent US 12,208,089
Granted Patent B2
US 12,208,089 · App. 17/330,143 · Granted Jan 28, 2025

Adjusting expression level of a gene encoding a Sirtuin protein by treating a human subject with a nitroxide

Inventor: Louis Habash (Irvine, CA)
A61K31/445
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,208,089
App. No.
17/330,143
Granted
Jan 28, 2025
Kind
B2
Abstract

Some embodiments disclosed herein include a method for increasing an expression level of a gene. The methods include administering an effective amount of a nitroxide antioxidant to a human subject having a decreased expression level of SIRT2, whereby expression level of the gene is increased.

Claims (17)

1. A method of increasing expression level of a gene encoding SIRT2 in a human subject, the method comprising:

identifying a human subject having both a decreased expression level of a gene encoding SIRT2 compared to a population of individuals of the same sex and similar age, and a disease or condition associated with decreased expression level of the gene encoding SIRT2, wherein the disease or condition is selected from the group consisting of systemic lupus erythematosus (SLE), cataracts, and osteoporosis; and

administering an effective amount of a nitroxide antioxidant to the subject, the nitroxide antioxidant selected from the group consisting of 2-ethyl-2,5,5-trimethyl-3-oxazolidine-1-oxyl (OXANO), 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), 4-amino-2,2,6,6-tetramethyl-1-piperidinyloxy (Tempamine), 3-Amin omethyl-PROXYL, 3-Cyano-PROXYL, 3-Carbamoyl-PROXYL, 3-Carboxy-PROXYL, 4-Oxo-TEMPO, 2,2,6,6-tetramethyl-4-oxo-1-piperidinyloxy (TEMPONE), 1-Hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine HCI (TEMPONE-H), 1,2-dipalmitoyl-sn-glycero-3-phospho (tempo) choline (TEMPO PC), and (4-[N,N-dimethyl-N-(2-hydroxyethyl)]ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO Choline),

whereby the administration of the nitroxide antioxidant increases the expression level of the gene encoding SIRT2.

2. The method of claim 1 , wherein the nitroxide antioxidant is TEMPOL.

3. The method of claim 1 , wherein the nitroxide antioxidant is OXANO.

4. The method of claim 1 , wherein the nitroxide antioxidant is TEMPO.

5. The method of claim 1 , wherein the nitroxide antioxidant is Tempamine.

6. The method of claim 1 , wherein the nitroxide antioxidant is TEMPONE.

7. The method of claim 1 , wherein the nitroxide antioxidant is TEMPONE-H.

8. The method of claim 1 , wherein the nitroxide antioxidant is TEMPO PC.

9. The method of claim 1 , wherein the nitroxide antioxidant is 3-Carboxy-PROXYL.

10. The method of claim 1 , wherein the nitroxide antioxidant is TEMPO Choline.

11. The method of claim 1 , wherein identifying a human subject having a decreased expression level of a gene encoding SIRT2 compared to a population of individuals of the same sex and similar age comprises measuring the expression level of the gene encoding SIRT2.

12. The method of claim 1 , wherein the disease or condition is SLE.

13. The method of claim 1 , wherein the disease or condition is cataracts.

14. The method of claim 1 , wherein the disease or condition is osteoporosis.

Continuity (1)
Related Publication 20220378765A1 · Dec 1, 2022
References Cited (53)
US 5352442A · Proctor · 1994 [cited by applicant]
US 5462946A · Mitchell et al. · 1995 [cited by applicant]
US 6096759A · Wilcox · 2000 [cited by examiner]
US 7153866B1 · Mitchell · 2006 [cited by examiner]
US 8778969B2 · Proctor · 2014 [cited by examiner]
US 9101619B2 · Habash · 2015 [cited by examiner]
US 9314457B2 · Gibson · 2016 [cited by examiner]
US 9522143B2 · Habash · 2016 [cited by examiner]
US 9522144B2 · Habash · 2016 [cited by examiner]
US 9545398B1 · Habash · 2017 [cited by examiner]
US 9579311B1 · Habash · 2017 [cited by examiner]
US 9700550B1 · Habash · 2017 [cited by examiner]
US 9744162B1 · Habash · 2017 [cited by examiner]
US 9937162B2 · Gibson · 2018 [cited by examiner]
US 10064852B2 · Habash · 2018 [cited by examiner]
US 10159665B2 · Habash · 2018 [cited by examiner]
US 10231959B2 · Habash · 2019 [cited by examiner]
US 10245256B2 · Habash · 2019 [cited by examiner]
US 10441568B2 · Goldstein et al. · 2019 [cited by applicant]
US 10441578B2 · Habash · 2019 [cited by examiner]
US 10828291B2 · Habash · 2020 [cited by examiner]
US 10874654B2 · Habash · 2020 [cited by examiner]
US 11324737B1 · Habash · 2022 [cited by examiner]
US 11510913B1 · Habash · 2022 [cited by examiner]
US 20080319014A1 · Habash · 2008 [cited by examiner]
US 20090209581A1 · Habash · 2009 [cited by examiner]
US 20120046314A1 · Habash · 2012 [cited by examiner]
US 20180078538A1 · Habash · 2018 [cited by examiner]
US 20190224178A1 · Habash · 2019 [cited by examiner]
US 20190224179A1 · Habash · 2019 [cited by examiner]
Tang et al. Circulation, Nov. 21, 2017, vol. 136, No. 21, pp. 2051-2067 (Year: 2017). [cited by examiner]
Soule et al. Free Radical Biology & Medicine, 2007, vol. 42, pp. 1632-1650 (Year: 2007). [cited by examiner]
Yamamoto et al. Molecular Endocrinology, 2007, vol. 21, No. 8, pp. 1745-1755 (Year: 2007). [cited by examiner]
Machado de Oliveira et al. Frontiers in Pharmacology, May 2012, vol. 3, Article 82, 9 pages (Year: 2012). [cited by examiner]
Teena et al. Biomolecules, 2020, 10, 1466; doi:10.3390/biom10101466, 16 pages (Year: 2020). [cited by examiner]
Yu et al. J. Neurochem., 2016, vol. 137, pp. 371-383 (Year: 2016). [cited by examiner]
Rizzi et al. International Journal of Cardiology, 2013, vol. 165, pp. 165-173 (Year: 2013). [cited by examiner]
Ritchie et al. Journal of Molecular and Cellular Cardiology, 2007, vol. 42, pp. 1119-1128 (Year: 2007). [cited by examiner]
Negrini et al. Nature Reviews Molecular Cell Biology, 2010, vol. 11, pp. 220-228 (Year: 2010). [cited by examiner]
Oliveira (Journal of Neurochemistry, 2010, vol. 114, pp. 1-12) (Year: 2010). [cited by examiner]
Kitada et al. Frontiers in Endocrinology, Mar. 2019, vol. 10, article 187, 12 pages (Year: 2019). [cited by examiner]
Martinez-Jimenez et al. (Diabetes Metab. Syndr. Jan.-Feb. 2019;13(1):582-589; Epub Nov. 10, 2018) (Year: 2019). [cited by examiner]
Hiratsuka et al. (Biochemical and Biophysical Research Communications, 2003, vol. 309, p. 558-566) (Year: 2003). [cited by examiner]
Kitada, et al., Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function. Front. Endocrinol., Mar. 27, 2019 | https://doi.org/10.3389/fendo.2019.00187. [cited by applicant]
Sarikhan et al. “SIRT2 deacetylase represses NFAT transcription factor to maintain cardiac homeostasis.” The Journal of biological chemistry vol. 293,14 (2018): 5281-5294. doi:10.1074/jbc.RA117.000915. [cited by applicant]
Lantier et al. SIRT2 knockout exacerbates insulin resistance in high fat-fed mice. PloS one vol. 13,12 e0208634. Dec. 11, 2018, doi:10.1371/journal.pone.0208634. [cited by applicant]
Park, et al., SIRT2 is a tumor suppressor that connects aging, acetylome, cell cycle signaling, and carcinogenesis. Translational Cancer Research, (2012); 1(1), 15-21. DOI: 10.3978/j.issn.2218-676X.2012.05.01. [cited by applicant]
De Oliveira, et al. “SIRT2 as a Therapeutic Target for Age-Related Disorders.” Frontiers in pharmacology vol. 3 82. May 3, 2012, doi: 10.3389/fphar.2012.00082. [cited by applicant]
Zhang, et al. “The Clinical Significance of SIRT2 in Malignancies: A Tumor Suppressor or an Oncogene ?. ” Frontiers in oncology vol. 10 1721. Sep. 8, 2020, doi:10.3389/fonc.2020.01721. [cited by applicant]
Wang, et al. “Downregulation of SIRT2 by Chronic Stress Reduces Expression of Synaptic Plasticity-related Genes through the Upregulation of Ehmt2.” Experimental neurobiology vol. 28,4 (2019): 537-546. doi:10.5607/en.201… [cited by applicant]
Donato et al., Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease, Circulation Research, Sep. 14, 2018, vol. 123, pp. 825-848. [cited by applicant]
Yu et al., High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects, Journal of Neurochemistry, 2016, vol. 137, Iss. 3, pp. 371-383. [cited by applicant]
International Search Report and Written Opinion for PCT/US2022/030066 issued Sep. 1, 2022. [cited by applicant]