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

Authors
Zorzopulos, Jorge; Opal, Steven M.; Hernando Insúa, Andrés; Rodriguez, Juan M.; Elías, Fernanda; Fló, Juan; López, Ricardo A.; Chasseing, Norma Alejandra; Lux, Victoria Adela R.; Coronel, Maria Florencia; Franco, Raul; Montaner, Alejandro D; Horn, David L
Publication Year
2017
Language
English
Format
article
Status
Published version
Description
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.
Fil: Zorzopulos, Jorge. Immunotech; Argentina
Fil: Opal, Steven M.. Memorial Hospital of Rhode Island; Estados Unidos. Alpert Medical School; Estados Unidos
Fil: Hernando Insúa, Andrés. Fundación Pablo Cassara; Argentina
Fil: Rodriguez, Juan M.. Fundación Pablo Cassara; Argentina
Fil: Elías, Fernanda. Fundación Pablo Cassara; Argentina
Fil: Fló, Juan. Immunotech; Argentina
Fil: López, Ricardo A.. Imunotech; Argentina
Fil: Chasseing, Norma Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Lux, Victoria Adela R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Coronel, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Franco, Raul. Imunotech; Argentina
Fil: Montaner, Alejandro D. Fundación Pablo Cassara; Argentina
Fil: Horn, David L. David Horn Llc; Estados Unidos
Subject
IMT504
MESENCHYMAL STEM CELLS
Bioquímica y Biología Molecular
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Patología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/24562