Table 4. Experimental therapeutic targets in FLD.
| Target | Mechanism | Agent | Ref. |
|---|---|---|---|
| Somatostatin receptors | Block of cAMP signalling through binding to somatostatin receptors | Pasireotide1 | (79) |
| Octreotide1 | (79,80) | ||
| Intracellular Ca++ levels and toxic bile acids | Block of cAMP signalling by increasing intracellular Ca++ | UDCA2 | (81) |
| TRPV4 agonist2 | (82) | ||
| Matrix metalloproteases (MMPs) | Inhibition of MMP function | Marimastat3 | (83) |
| PPARγ | Inhibition of ERK1/2 and mTOR–S6 kinase signalling pathways | Pioglitazione4 | (84) |
| Telmisartan4 | (84,85) | ||
| Macrophages | Direct inhibition of monocyte-macrophage transdifferentiation | Clodronate5 | (31) |
| CXCR3 | Inhibition of monocyte recruitment acting on the CXCL10 receptor | AMG-4875 | (30) |
Adapted from (29). 1, octreotide and pasireotide demonstrated to slow hepatic cyst growth and to reduce peribiliary fibrosis in PCK rats. Clinical trials in phase I-II are currently ongoing in polycystic liver disease (octreotide in NCT00426153, pasireotide in NCT01670110); 2, ursodeoxycholic acid (UDCA) and transient receptor potential cation channel subfamily V (TRPV4) agonist are strategies under investigation acting both on the same pathways; 3, marimastat decreased hepatic cystogenesis both in vitro and in PCK rats; 4, pioglitazone and telmisartan, agonists of peroxisome proliferator-activated receptor-γ (PPARγ), showed efficacy in reducing cyst area, cholangiocyte proliferation and pericystic fibrosis in PCK rats; 5, bisphosphonate clodronate and AMG-487 were able to reduce either cyst growth or pericystic inflammation and fibrosis in Pkhd1del4/del4 mice.