The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice

Mark D. Minden; Cindy Audiger; Geneviève Chabot-Roy; Sylvie Lesage; Jean-Sébastien Delisle; Barbara Biemans; Violetta Dimitriadou

doi:10.12659/AOT.945249

05 November 2024 : Original article

The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice

Mark D. Minden^1ABCDE, Cindy Audiger^23BCDE, Geneviève Chabot-Roy^2BCDE, Sylvie Lesage

^23ABCDE, Jean-Sébastien Delisle

^24BCDE, Barbara Biemans^5ADE, Violetta Dimitriadou^5ABCDE*

DOI: 10.12659/AOT.945249

Ann Transplant 2024; 29:e945249

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Table 1 Treatment regimens.

Group designation	Cytarabine				Apraglutide/hGLP-2/vehicle				No. of main animals (age)	No. of recovery animals
Group designation	Dose level (mg/kg)	Dose frequency	Treatment days	Dose volume (mL/kg)/route	Dose level (mg/kg)	Dose frequency	Treatment days	Dose volume (mL/kg)/route	No. of main animals (age)	No. of recovery animals

Vehicle control	0				0	Once daily	−4 to +12	10/SC	(12–18 weeks)
Cytarabine only	30	Twice daily	0 to +4	10/IP	0				15	3
Co-apraglutide/cytarabine	30	Twice daily	0 to +4	10/IP	3.3	Once every 24 hours	0 to +12	10/SC	10
Pre- + co-apraglutide/cytarabine	30	Twice daily	0 to +4	10/IP	3.3	Once every 24 hours	1–4 -+12	10/SC	15	3
Pre- + co-apraglutide/cytarabine	30	Twice daily	0 to +4	10/IP	3.3	Once every 48 to 72 hours	−4, −2, 0, 3, 6, 9, 12	10/SC	10

Vehicle control					0	Once daily	4		22 (8–11 wo)
Cytarabine only	30	Twice daily	0 to +4						22 (8–11 wo)
Apraglutide/cytarabine	30	Twice daily	0 to +4		0.11	Once daily	−4 to +4		22 (8–11 wo)
Apraglutide/cytarabine	30	Twice daily	0 to +4		0.33	Once daily	−4 to +4		22 (8–11 wo)
Apraglutide/cytarabine	30	Twice daily	0 to +4		1.1	Once daily	−4 to +4		22 (8–11 wo)
hGLP-2/cytarabine	30	Twice daily	0 to +4		0.6 mg/kg	Once daily	−4 to +4		22 (8–11 wo)	–


Vehicle control	0	–	–	–	0	Once every 48 hours	−8, −6, −4, −2, 0, 2, 4, 6	10/SC	10	–
Melphalan only	17.5	Single dose	0	10/IP	0	-	-	-	10	–
Apraglutide/melphalan	17.5	Single dose	0	10/IP	3.3	Once every 48 hours	−8, −6, −4, −2, 0, 2, 4, 6	10/SC	10	v
Apraglutide/melphalan	17.5	Single dose	0	10/IP	17.5	Once every 48 hours	−8, −6, −4, −2, 0, 2, 4, 6	10/SC	4	–
Allogeneic transplant/apraglutide	8.5 (Exp. 1); (7 Exp. 2)	Single dose	−1 (TBI), 0 (BMT)	10 BM; 2.5 SPL	3.3	Once every 48 hours	−9, −7, −5, −3, −1, 1, 3, 5, 7	300/SC	10 (Exp.1); 10 (Exp.2)
Allogeneic transplant/control	8.5 (Exp. 1); 7 (Exp. 2)	Single dose	−1 (TBI), 0 (BMT)	10 BM; 2.5 SPL	0	Once every 48 hours	−9, −7, −5, −3, −1, 1, 3, 5, 7	300/SC	10 (Exp.1); 10 (Exp.2)
Transplant control/control	0				0	Once every 48 hours	−9, −7, −5, −3, −1, 1, 3, 5, 7	300/SC	5 (Exp.2)
BM – bone marrow; Exp. – experiment; IP – intraperitoneal; SC – subcutaneous; SPL – spleen; wo – week old. NOD/SCID mice were gamma irradiated and injected with 5 million human leukemia cells via the tail vein on day −48.

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The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice

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