CHST-15 siRNAは生体ブタ食道の66%の粘膜を切除モデルを計30頭のブタに対して行った。この中でCHST-15 siRNAの投与により、3週間後の粘膜収縮率が有意に軽度でCHST-15 siRNAは食道粘膜切除術後の狭窄を生理食塩水投与に比して有意に予防することが明らかになった。また、250nM、2,500nM、25,000nMの各濃度の投与を行うモデルにおいて、３週間後の粘膜収縮率は2,500nMで薬効はプラトーに達することが明らかになった。さらに既存治療である副腎皮質ステロイドの投与で見られた食道壁の壊死や膿瘍形成などのような有害事象も来さないことを明らかにした。
CHST-15 siRNA was used in 66% of the mucosa of the living pig esophagus was excised in a total of 30 pigs. Among them, administration of CHST-15 siRNA significantly prevented stenosis after esophageal mucosal resection compared to saline administration, with a significantly milder (P<0.01). In a model in which 250 nM, 2,500 nM, and 25,000 nM concentrations were administered, mucosal shrinkage rates after 3 weeks were 55.2 ± 5.1%, 40.3 ± 3.9%, and 38.8 ± 7.1%, respectively, indicating that the efficacy of the drug reached a plateau at 2,500 nM. Furthermore, the study showed that the drug did not cause necrosis of the esophageal wall and abscess formation, which have been observed with existing treatments such as corticosteroids. We believe that we have provided proof of concept for our study that CHST-15 siRNA, a novel nucleic acid drug, can inhibit stricture and scar formation after gastrointestinal endoscopy.
|
