Disease Information

General Information of the Disease (ID: DIS00272)

Name	Amyotrophic lateral sclerosis
ICD	ICD-11: 8B60
Resistance Map

Type(s) of Resistant Mechanism of This Disease

IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

Click to Show/Hide the Full List of Drugs

Riluzole

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[1]
Resistant Disease	Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
Molecule Alteration	Expression		Up-regulation	Molecule Info
Resistant Drug	Riluzole			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	bEND.3 cells	Brain	Homo sapiens (Human)	CVCL_0170
	C8D1A cells	Colon	Mus musculus (Mouse)	CVCL_6379
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	High-performance liquid chromatography
Mechanism Description	Riluzole is moderately effective for ALS patients and prolongs survival by only three months. According to previous studies, increased P-gp transporter activity and expression are induced by ALS. As riluzole is a substrate of P-gp, the inductions potentially limit the brain distribution of riluzole and further promote drug resistance in the later stage of ALS disease.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1)				[1]
Sensitive Disease	Amyotrophic lateral sclerosis [ICD-11: 8B60.0]
Molecule Alteration	Expression		Down-regulation	Molecule Info
Sensitive Drug	Riluzole			Drug Info
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	bEND.3 cells	Brain	Homo sapiens (Human)	CVCL_0170
	C8D1A cells	Colon	Mus musculus (Mouse)	CVCL_6379
Experiment for Molecule Alteration	Western blotting analysis
Experiment for Drug Resistance	High-performance liquid chromatography
Mechanism Description	BEND.3 Cells were treated with riluzole and verapamil liposomes at different doses and time durations to determine the inhibitory levels of P-gp. In the buffer control treatment, the expression of P-gp was noted as a baseline level (100%). After the exposure to 5, 10, 20, 30, and 40 ug/ml cocktail liposomes for 48 h, bEND.3 cells resulted in a distinct decrease of P-gp expression with 93.0 plus or minus 5.2%, 85.8 plus or minus 4.7%, 50.3 plus or minus 5.6% 26.2 plus or minus 5.1%, and 20.8 plus or minus 4.9% of the baseline level, respectively. The extent of the decrease was linearly dependent on the concentration of verapamil in formulations (5 to 30 ug/ml), while inhibited levels of P-gp by 30 ug/ml and 40 ug/ml of verapamil cocktail liposome were not significantly different.

References

Ref 1	Verapamil and riluzole cocktail liposomes overcome pharmacoresistance by inhibiting P-glycoprotein in brain endothelial and astrocyte cells: A potent approach to treat amyotrophic lateral sclerosis .Eur J Pharm Sci. 2018 Jul 30;120:30-39. doi: 10.1016/j.ejps.2018.04.026. Epub 2018 Apr 26. 10.1016/j.ejps.2018.04.026