Experts are developing groundbreaking therapies called host-directed therapies (HDT) to combat tuberculosis (TB) by harnessing the body's immune system, even against drug-resistant strains of the disease.
Associate Professor Susanna Brighenti from the Centre for Infectious Medicine (CIM), ANA Futura at the Karolinska Institutet, Stockholm, Sweden, is set to present her findings at this year's ESCMID Global Congress in Barcelona.
In 2022, there were 7.5 million newly diagnosed cases of TB globally, resulting in an estimated 1.3 million deaths. Multidrug-resistant TB (MDR-TB) accounted for approximately 410,000 cases and 160,000 deaths.
Assoc Professor Brighenti explains, "Mycobacterium tuberculosis (Mtb) has evolved mechanisms to evade the human immune response and resist antimicrobial treatments. While new antimicrobial therapies are emerging, the standard antibiotic treatment for TB remains arduous and lengthy, particularly for drug-resistant strains. Therefore, adjunct treatments are essential."
HDTs aim to bolster the body's immune response to TB, particularly MDR-TB, by targeting various immune pathways in infected cells. These therapies aim to restore or induce antimicrobial functions in host immune cells rather than directly inhibiting bacterial growth.
Assoc Professor Brighenti's research has identified small molecule compounds, including histone deacetylase (HDAC) inhibitors, which can enhance the expression of proteins associated with antibacterial defense. These compounds have shown promise in reducing Mtb growth inside immune cells by 50-75%, even without antibiotics.
She emphasizes, "These immunomodulatory compounds could complement standard therapy, potentially reducing the dosage and duration of antibiotic treatment, thereby improving patient outcomes."
By combining existing antibiotics with immune-enhancing compounds, the effect of antibiotics could be preserved while promoting clinical recovery and limiting inflammation and immunosuppression in TB patients.
Assoc Prof Brighenti believes that implementing immunotherapy alongside standard therapy could revolutionize TB treatment, similar to its impact on cancer and autoimmune diseases. Short-term, approved therapeutics could be used initially, followed by more precise immunomodulatory interventions tailored to individual patient needs in the long term.
It's clear that personalized medicine will play a crucial role in the future management of TB, ensuring that treatments are optimized for each patient's unique circumstances.
