Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

ZORZOPULOS J; OPAL MS; HERNANDO INSÚA A; RODRIGUEZ JM; ELÍAS F; FLÓ J; LÓPEZ RA; CHASSEING NA; LUX-LANTOS VA; CORONEL MF; RAUL FRANCO; ELÍAS F; MONTANER AD; DAVID HORN

World Journal of Stem Cells

Baishideng Publishing Group Inc.

Lugar: Pleasanton, CA 94588; Año: 2017 vol. 9 p. 45 - 67

The immune responses of humans and animals to insults (i.e. infections, traumas, tumoral transformation, and radiation) are based on an intrincate 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 demonstrated to be an effective therapy in preclinical studies representing 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, expectations of great medical benefit have not been yet 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 thusfar, IMT504 has been well-tolerated, even in 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 likely would benefit from an immunoprotective/immunoregenerative therapy.