Table 3.
Strategies that reverse new-onset diabetes in nonobese diabetic mice (2005–present).
| Agent | Details | Disease reversal | Ref. | ||
|---|---|---|---|---|---|
| Number | % |
Follow-up (weeks) |
|||
| FTY720 | Sphingosine-1-phosphate analog; 3 mg/kg by oral gavage daily | 5/10 | 50 | 24 | [151] |
| EGF plus gastrin | 1 µg/kg/day EGF plus 3 µg/kg/day gastrin ip.; 2 injections/day for 2 weeks | 5/6 | 83 | 12 | [67] |
| Anti-CD3 plus hInsB24-C4 | 40 µg anti-CD3 F(ab’)2 (145–2C11) iv. on days 0–4 plus 40 µg hInsB24-C4 in. on days 0, 2, 7 and 12 | 17/31 | 55 | 9 | [64] |
| Lisofylline plus exendin-4 | 27 mg/kg/day lisofylline plus 18 nM/day exendin-4 sc. by osmotic mini-pump for 28 days | 5/9 | 56 | 24 | [66] |
| Insulin-coupled fixed splenocytes | 5 × 107 cells iv. | 10/19 | 53 | 25 | [18] |
| Regulatory T cells | CD4+CD25+CD62L+ cells from NOD.BDC2.5 mice expanded in vitro with antigen-pulsed DCs and IL-2; 0.8–1.5 × 106 cells on days 0 and 14 | 4/11 | 36 | 24 | [157] |
| Anti-CD3 plus exendin-4 | 10 µg anti-CD3 (145–2C11) iv. for 5 days plus 0.075 µg exendin-4 ip. for 10 days | 20/45 | 44 | 3 | [65] |
| Anti-human CD20 | NOD/hCD20 mice; B cell-depleting anti-hCD20 (2H7); 500 µg followed by 3 injections of 250 µg at 3-day intervals | 4/14 | 29 | 19 | [56] |
| Microspheres carrying antisense oligonucleotides | Antisense oligonucleotides to CD40, CD80 and CD86; sc. proximal to pancreatic lymph nodes 2-times/week for 25 days | 7/15 | 47 | 8 | [163] |
| α1-antitrypsin (Aralast™) | 2 mg ip. every 3 days; 5 injections | 21/24 | 88 | 39 | [179] |
| Cytotoxin-coupled anti-CD22 | B cell-depleting N-acetyl-calicheamicin dimethyl acid-conjugated anti-CD22 (Cy34.1); 160 µg/kg ip.; 2 injections, 5 days apart | 6/10 | 60 | 14 | [60] |
| Imatinib (Gleevec®) | 1.5 mg by oral gavage daily for 10 weeks | 8/17 | 47 | 35 | [168] |
| Sunitinib (Sutent®) | 2 mg by oral gavage daily for 9 weeks | 5/6 | 83 | 9 | [168] |
| GLP-1 plus gastrin | 100 µg/kg GLP-1 plus 1.5 µg/kg gastrin ip. twice daily for 3 weeks | 7/7 | 100 | 8 | [68] |
| DPP-4 inhibitor plus proton pump inhibitor | 10 mg/kg DPP-4 inhibitor by oral gavage once daily plus 30 mg/kg proton pump inhibitor sc. twice daily for 12 weeks | 6/8 | 75 | 12 | [69] |
| Nanoparticles carrying peptide/MHC complexes | NRP-V7/H-2Kd or MimA2/H-2Db; NRP-V7 and MimA2 are mimotopes of IGRP206–214 and DMK138–146, respectively; iv. 2-times/week until euglycemic for 4 weeks | 8/11 | 73 | 13 | [180] |
Studies are listed in chronological order. All employed female NOD mice except where noted. Follow-up for disease reversal is from time of disease onset. In some studies, mice were treated with insulin that was later withdrawn; see references for details.
DMK: Dystrophia myotonica kinase; DPP: Dipeptidyl peptidase; GLP: Glucagon-like peptide; hIns: Human insulin; IGRP: Islet-specific glucose-6-phosphatase catalytic subunit-related protein; in.: Intranasally; ip.: Intraperitoneally; iv.: Intravenously; NOD: Nonobese diabetic; PDGFR: PDGF receptor; sc.: Subcutaneously.