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We are studying the rejuvenating effect of a drug Entolimod on the immune system of dogs

May 20, 2022


The study of the rejuvenating effect of an immunostimulatory drug Entolimod will allow us to learn more about age-related changes in a dog’s immune system while testing ways to correct unfavorable ones. Preliminary results of this research direction are expected by the end of this summer.


What’s the problem?


The older we get, the easier it is for infections to attack us. We have all seen how, at the peak of the coronavirus pandemic, people over the age of 65 were more likely to become infected, suffered more from the disease, and had a higher risk of death. This risk is not just a coronavirus-related problem and is not only true for humans. All mammals, including dogs, also experience a decline in immune functions and become more vulnerable to infections as they age.


Curiously, the aged immune system does not give up entirely. While its ability to battle infections weakens, the immune system in other ways stays on alert and becomes prone to “systemic inflammation,” a typical pathological condition during aging.


The hyperreactivity of the aged immune system is manifested by the release of alarming proteins called cytokines. The cytokine release drives many unpleasant physical symptoms we experience during infections, like fever, running nose, swelling, sore throat, muscle ache, etc.


Typically, in response to such signals, the immune system recruits and activates the needed number of immune cells to fight the disease. But if cytokine release exceeds the normal range, it may become uncontrolled (the phenomenon named the cytokine storm), leading to acute inflammation associated with massive death of healthy cells. This dangerous situation can lead to a septic shock that could be lethal. The aged immune system is prone to developing this pathological reaction making septic shock one of the significant risks for the elderly.


Finding a solution


Our goal is to rejuvenate the immune system of our dogs to make all its components work effectively and in a balanced way. For this purpose, we chose a drug named Entolimod. Entolimod stimulates the immune system and was invented almost 20 years ago by researchers at Cleveland Clinic as a powerful antidote against radiation injuries.


We hypothesize that, beyond protecting against radiation sickness, Entolimod can also treat the age-related decline of the immune system. Scientists call this decline immunosenescence.


How exactly does Entolimod work? It ramps up hematopoiesis—the formation, development, and maturation of blood cells: red blood cells, white blood cells, and platelets. Earlier on, the developers studied the drug on mice, and experiments confirmed that old mice began to age more slowly after receiving a short course and responded better to vaccination. A clinical trial of Entolimod in elderly humans is currently underway at Mayo Clinic.


What we are doing


In January 2022, we launched the Entolimod study on our dogs. We divided our dogs into two groups: the first was injected with Entolimod, and the second received a placebo. By the end of this summer, we plan to get data on how the drug affected the immune system and whether it will be able to improve the basic parameters compared to the dogs who received a placebo.


In addition to studying the drug's effects, we will collect new data on changes in various parameters of the immune system and learn more about age-related changes in dogs—this area remains little studied.


We look forward to publicly sharing the results of this study. Our team continues to look for ways to prolong the life of our pets.


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Scientific background


If you want to learn more about our research and you’re not put off by scientific language, explore the following articles:


Haderski, Gary J et al. “TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects.” PloS one vol. 15,2 e0227940. 6 Feb. 2020, doi:10.1371/journal.pone.0227940


Yoon SI, Kurnasov O, Natarajan V, Hong M, Gudkov AV, Osterman AL, Wilson IA. Structural basis of TLR5-flagellin recognition and signaling. Science. 2012 Feb 17;335(6070):859-64. doi: 10.1126/science.1215584. PMID: 22344444; PMCID: PMC3406927.


Krivokrysenko, Vadim I et al. “The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.” PloS one vol. 10,9 e0135388. 14 Sep. 2015, doi:10.1371/journal.pone.0135388


Clinical Trial: Entolimod on Immunosenescence in Healthy Geriatric Subjects Receiving Influenza Vaccination



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Vaika's fundamental goal is improving the health of aged animals. We do not limit our activities to Aging Sled Dog Study but are open for collaborations and are always eager to help other researchers