Dr. Santiago Ramón-García
Dr. Santiago Ramón-García, an innovator in global health, with the support of RESULTS Canada recently received a grant through Grand Challenges Canada toward his tuberculosis (TB) research work that will undoubtedly make life-saving impacts on TB treatment, especially to treat the drug resistant forms of the disease (MDR- and XDR-TB), for which there are no effective therapies available.
Santiago had always been concerned with global health disparities, but it was during his undergraduate studies that he formed a passion for TB research. It was at the University of Zaragoza in Spain that he met Dr. José A. Aínsa who was studying antibiotic resistance in Mycobacterium tuberculosis and, interested in Dr. Aínsa’s research, Santiago decided to pursue a TB-focused PhD. “I was interested in learning more and I also thought this could be my small contribution to give back to the world,” says Santiago. “We have to be grateful for the opportunities we have been given just from being born in a developed country.”
Dr. Ramón-García’s new grant will aid his work in finding new therapeutic drug combinations to treat TB to shorten the current tedious and long TB treatment regimen and also highlighting the staggering impact of multi-drug resistant TB.
Santiago wants to bring awareness of tuberculosis as one of the most devastating diseases in the world that kills nearly two million people each year and 1/3 of the global population is infected, and move away from the misconception that TB is a “disease of the past.” He also wants to remind others that - while TB is curable - currently very few drugs are effective and the treatment is long (six months), with uncomfortable side effects. One story that struck Santiago in particular was of patients with extensively drug-resistant TB (XDR-TB) in South Africa who were forced to remain in a hospital surrounded with barbed wire to prevent the patients from escaping and transmitting an almost untreatable disease to their communities. “It is clear that we need new therapies to make standard TB treatment shorter and to treat multidrug-resistant TB and extensively drug-resistant TB patients more effectively,” said Santiago. For this reason, part of his research focuses on emerging, hard-to-treat strains that, even with a very aggressive toxic drug therapy, take years to be cured.
The lack of substantial antibiotics to treat drug-resistant TB and the significant delay and cost of bringing new drugs onto the market (the last discovered TB drug was approved in the 1960s) alarms Santiago, but it also motivates his work. In his research program, he uses an unconventional innovative approach: to identify new synergistic combinatorial TB therapies using clinically approved drugs. Identification of synergistic combinations using drugs approved for other therapeutic applications can allow the introduction of new TB therapies in shorter time. Because these drugs have known properties and safety profiles, any newly identified combination could be rapidly evaluated in clinical trials.
Santiago uses the analogy “2+2=16” to illustrate how these drug combinations work: every drug alone may not be effective to treat TB, but - when put in combination - their activities synergize, and the effect becomes greater than the sum of the individual drug contributions and, now effective against TB.
Video and resources: Dr. Ramón-García encourages others to watch this two-minute video, addressed to the general public, explaining his research’s approach and, his recently published paper on the subject here. To view to the journal Antimicrobial Agents & Chemotherapy thatrecently published the foundations of he and his team’s work, click here.
Encouraged by results showing that synergistic drug combinations are quite common, Santiago and his research team are extending their screening program and many promising new combinations are in the pipeline. Dr. Ramón-García’s new grant will allow him to test two synergistic drug combinations in vivo. Proving their concept works in vivo will open the door to clinical studies and also the validation of more new combinations.
Santiago is most excited about using the new drug combinations to treat patients in collaboration with a leading drug testing clinic in South Africa (Dr. Andreas Diacon). MDR-TB and XDR-TB strains isolated from critically ill patients will be tested for sensitivity to the drug combination, followed by Early Bactericidal Activity (EBA) testing in patients. These experiments could quickly lead to clinical trials.
“Developing new drugs (or drug combinations) for TB therapy is only the first step,” said Santiago. “To really deliver them to the people who most need it in a global approach we need ‘Integrated Innovation.’” “Integrated innovation” is a concept developed by Grand Challenges Canada. It is the coordinated application of scientific/technological, social and business innovation to develop solutions to complex challenges, from the coordinated and willing efforts of many parties. Santiago is optimistic that his work will generate interest to form a collaboration with the Global Fund to Fight AIDS, Tuberculosis and Malaria and the Canadian International Development Agency. This could help moving faster toward his goal.
“I consider myself a normal person with normal skills. While skills are always an asset, I think the critical point is willingness to make a difference. Any person can do it. We just need to always evolve, not become stagnant, and get involved,” said Santiago.
Santiago discussed his role as a global health innovator and champion, and offered this advice: “Full commitment, perseverance, and passion are what drive a career. We need passionate and committed people in all aspects of our society but, more specifically, in the field of TB and neglected diseases. We also need believers: people that truly believe that with hard work a difference can be made for the good of our world - in this case to fight TB. When I see and read stories of patients with TB and the harsh situations they go through, they are my inspiration and the reason I happily go to work every day.”
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