Tracing the virus could be key to drug options for kidney transplants

by Dr. Gregor Bond

More than 15,000 Europeans undergo kidney transplants on average each year, and while medical advances have helped many recipients enjoy healthy lives, the risks of organ rejection and infection remain major challenges.

With every transplant, success depends on using balanced doses of immunosuppressive drugs to reduce the risk of infection and graft rejection. Decades of clinical trials, and the keen instincts of medical practitioners, tell us that there is an average dose level of a drug needed to support patient care and comfort.

However, this ‘golden middle’ dose is not an exact science.

This is partly because healthcare providers currently have no way of measuring the immune system to determine whether the organ recipient needs more or less immunosuppressant.

Tracking Torque Teno virus to minimize transplant rejection

That could change, thanks to research conducted by leading kidney transplant specialists at 13 university transplant centers in Austria, Czech, France, Germany, the Netherlands and Spain. Since last August, they have been conducting clinical studies on using the common but little-known Torque Teno virus (TTV) as a tool to minimize rejection or infection.

The word ‘virus’ usually has negative associations, as we know from the tragic fight against the coronavirus. But the human body produces an army of ‘good’ bacteria that defend itself against the ‘bad’ bacteria. As for the Torque Teno virus, previous studies have established that it is present in nearly all humans but is apatogenic – in other words, harmless.

Individual drug dosage

Researchers involved in the kidney transplant study, in which I was a participant, believe that by tracking blood levels of Torque Teno virus, healthcare providers will finally have the tools to monitor transplant recipients’ immune system responses. Having a clearer picture of what’s going on will allow individualized doses of immunosuppressive drugs to significantly improve post-transplant care.

Transplant recipients rely on these drugs not only to control the immune system’s urge to reject foreign organs, but also to ward off infection. Therefore, finding an effective and relatively unobtrusive way to monitor the immune system and guide individual drug dosages would be a major step in helping reduce rejection and infection.

That’s where TTV comes into play. Research shows that a strong immune system can fend off TTV and reduce its concentration in the blood. Conversely, if a person’s immune system is weak or suppressed by drugs, the virus will spread more in the blood. Ongoing trials aim to show that a low concentration of TTV indicates a risk of organ rejection, while a high TTV load in the blood indicates a risk of infection.

If clinical trials prove that the use of TTV as an ‘immunometer’ is safe and effective, this will be a major development that could help doctors optimize patient care. During the trial, a specially developed PCR test was used to monitor participants’ blood levels of TTV. These tests are safe and relatively affordable, and are very similar to those used to check respiratory specimens for evidence of the coronavirus.

With support from the EU’s Horizon research and innovation fund, our research team worked with 260 kidney transplant recipients in participating clinics and hospitals. The first group of 130 was treated using conventional methods, while the second underwent TTV-guided dosing. No new surgical interventions were used, and the drugs are well established, so the trials pose little risk to participants. Nonetheless, safety is the top priority. There are strict safety protocols for drug dosing and an independent safety monitoring board conducts regular reviews.

The TTV team is not alone in exploring new ways to improve transplants and long-term care. Other respected researchers are also working to fine-tune the dosage of immunosuppressive drugs and reduce or eliminate the need for them. But it could be years before some of the most promising efforts are ready for clinical practice. Until then, new tools are needed to improve care for existing and future transplant recipients.

The TTV trial is still in its early stages and may need to be repeated outside the EU to collect more diverse data. But we believe a novel approach using ‘good’ viruses as a measure of immunity could yield positive results for organ transplant recipients.

Other medical fields where monitoring and controlling the immune system are critical to successful treatment, including oncology and rheumatology, may also be useful.

Even if the goal is not achieved, trial data and regular interactions between leading experts can be a springboard for other medical development breakthroughs. This is what is so exciting about the opportunity created by the EU’s Horizon program, and why pan-European research collaboration and support is so important for the future of healthcare in the EU – and around the world.

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