Name	Intervertebral disc degeneration
ICD	ICD-11: FA80

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Theses findings reveal an epigenetic interplay mechanism in NPC senescence and IVD degeneration, presenting a critical pro-senescence role of ALKBH5 and m6A hypomethylation, highlighting the therapeutic potential of targeting the m6A/DNA (cytosine-5)-methyltransferase 3B (DNMT3B)/E4F1 axis for treating IVD degeneration.
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Down regulation
In-vitro Model	Nucleus pulposus cell (The NP tissues were cut into pieces after collection during surgery)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[1]
Response Summary	Theses findings reveal an epigenetic interplay mechanism in NPC senescence and IVD degeneration, presenting a critical pro-senescence role of ALKBH5 and m6A hypomethylation, highlighting the therapeutic potential of targeting the m6A/DNMT3B/Transcription factor E4F1 (E4F1) axis for treating IVD degeneration.
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulator	RNA demethylase ALKBH5 (ALKBH5)		ERASER	Regulator Info
Target Regulation	Up regulation
In-vitro Model	Nucleus pulposus cell (The NP tissues were cut into pieces after collection during surgery)

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene				[5]
Response Summary	Subsequent loss- and gain-of-function experiments reveal WTAP is increased in senescent nucleus pulposus cells, and significantly promotes Long intergenic non-protein coding RNA 657 (NORAD) m6A modification. This study shows interruption of NORAD m6A modification or the NORAD/PUMILIO/E2F3 axis could serve as a potential therapeutic target to inhibit the senescence of NPCs and development of intervertebral disc degeneration(IVDD).
Responsed Disease	Intervertebral disc degeneration [ICD-11: FA80]
Target Regulator	Wilms tumor 1-associating protein (WTAP)		WRITER	Regulator Info
Pathway Response	Cellular senescence			hsa04218
Cell Process	Cell senescence
In-vitro Model	Nucleus pulposus cells (NPCs) (Nucleus pulposus cells)
In-vivo Model	After 50g male NORAD-KO or C57 mice at age of 8 weeks were anesthetized with 3% (w/v) pentobarbital (2 ml/kg) and grouped randomly, investigators blinded to the group allocation performed the experiment. The disc levels in rat tail (Co6/7, 7/8, and 8/9) were located by palpation on the coccygeal vertebrae and confirmed by trial radiography. Needles (33-G) were used to puncture the annulus fibrosus layer though the tail skin, in parallel to the end plates. To ensure that the needle did not penetrate too deeply , the length of the needle was pre-determined according to the dimensions of annulus fibrosus and the NP , which were measured in a preliminary experiment and found to be approximately 4 mm. Five kinds of solution were prepared for intradisc injection, including AA V vector, AAV containing shPUM1, AAV containing shPUM2 for Norad KO mice, AAV vector, AAV containing shE2F3, AAVcontaining OE-E2F3 for WT mice.

Ref 1	m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency. Clin Transl Med. 2022 Mar;12(3):e765. doi: 10.1002/ctm2.765.
Ref 2	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800020380)
Ref 3	The glutamate/cystine antiporter SLC7A11/xCT enhances cancer cell dependency on glucose by exporting glutamate. J Biol Chem. 2017 Aug 25;292(34):14240-14249. doi: 10.1074/jbc.M117.798405. Epub 2017 Jun 19.
Ref 4	Clinical pipeline report, company report or official report of Purple Biotech.
Ref 5	WTAP-mediated m(6)A modification of lncRNA NORAD promotes intervertebral disc degeneration. Nat Commun. 2022 Mar 18;13(1):1469. doi: 10.1038/s41467-022-28990-6.
Ref 6	Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95. doi: 10.1093/jnci/djt210. Epub 2013 Sep 23.
Ref 7	Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28.