The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

中文翻译：

---

免疫调节性寡核苷酸IMT504：对骨髓间充质干细胞的影响，作为一流的免疫保护/免疫再生疗法。

人和动物对侮辱的免疫反应（即，感染，创伤，肿瘤转化和放射）基于复杂的细胞和化学信使网络。侮辱后立即出现异常高的炎症，或引起慢性炎症的异常延长的促炎刺激会导致威胁生命或严重衰弱的疾病。在临床前研究中，间充质干细胞（MSC）移植已被证明是一种有效的治疗方法，该方法评估了多种炎性疾病。MSC可导致炎症消退，为再生和实际再生做准备，然后最终恢复到正常基线或体内平衡。但是，在移植的MSC的临床试验中，尚未实现对巨大医学益处的期望。作为MSC移植的实用替代方案，具有增强内源性MSC扩增和/或活化能力的合成药物也可能是有效的。关于这一点，IMT504是一类主要的免疫调节寡核苷酸的原型，可诱导MSCs的体内扩增，导致神经性疼痛，骨质疏松症，糖尿病和败血症的临床前模型显着改善。IMT504易于制造，并且具有出色的临床前安全记录。在迄今为止研究的少数患者中，即使在非常高的剂量下，IMT504也具有良好的耐受性。有必要进行进一步的临床研究，以证明IMT504可用于解决多种人类疾病中的炎症和再生，这些疾病可能会受益于免疫保护/免疫再生疗法。