Tuberculosis succumbs to a new strategy – C&EN

Tuberculosis and the Urgent Need for New Treatments Aligned with Sustainable Development Goals

Overview of Tuberculosis Impact

Tuberculosis (TB) remains the world’s deadliest infectious disease, with approximately 10.8 million people contracting TB and 1.25 million deaths reported in 2023, according to the World Health Organization. This public health challenge directly relates to Sustainable Development Goal (SDG) 3: Good Health and Well-being, which aims to end epidemics of communicable diseases including TB.

Innovative Compound JNJ-6640: A New Strategy Against TB

Scientists from Johnson & Johnson, the London School of Hygiene and Tropical Medicine, and multiple partners have discovered a novel compound, JNJ-6640, that targets Mycobacterium tuberculosis through a unique mechanism. This breakthrough supports SDG 3 by contributing to the development of effective treatments to combat TB.

Mechanism of Action and Scientific Significance

1. JNJ-6640 inhibits the enzyme amidophosphoribosyltransferase (PurF), essential for de novo purine biosynthesis in M. tuberculosis.
2. Purines are critical for nucleic acid synthesis, energy metabolism, and cellular signaling, making PurF a vital target.
3. Inhibiting PurF disrupts purine production, leading to bacterial death.

This approach challenges previous assumptions that targeting purine biosynthesis would be ineffective due to bacterial purine recycling, highlighting new avenues for drug discovery and innovation (SDG 9: Industry, Innovation, and Infrastructure).

Collaborative Research Efforts and Global Health Impact

• The project exemplifies international collaboration between pharmaceutical and academic institutions, reflecting SDG 17: Partnerships for the Goals.
• Support from the Gates Foundation’s Tuberculosis Drug Accelerator underscores the importance of funding and partnerships in addressing global health crises.
• Research findings indicate that JNJ-6640, when combined with existing TB drugs bedaquiline and pretomanid, enhances treatment efficacy in animal models.

Challenges and Future Directions

• JNJ-6640 exhibits poor metabolic stability and limited solubility, which must be addressed to develop viable drug candidates.
• Efforts are underway at the Holistic Drug Discovery and Development Centre (H3D) to design improved PurF inhibitors.
• The goal includes replacing linezolid, a current TB treatment drug with toxic side effects, thereby improving patient safety and treatment outcomes.

Contribution to Sustainable Development Goals

• SDG 3 (Good Health and Well-being): Advances in TB treatment directly reduce mortality and morbidity from infectious diseases.
• SDG 9 (Industry, Innovation, and Infrastructure): The discovery of JNJ-6640 represents innovative pharmaceutical research and development.
• SDG 17 (Partnerships for the Goals): The collaborative nature of the research highlights the critical role of global partnerships in achieving health targets.

Conclusion

The discovery of JNJ-6640 marks a promising step forward in the fight against tuberculosis, aligning with multiple Sustainable Development Goals aimed at improving global health through innovation and collaboration. Continued research and development are essential to overcome current challenges and translate this scientific advancement into effective, accessible treatments worldwide.

1. Sustainable Development Goals (SDGs) Addressed or Connected to the Issues Highlighted in the Article

1. SDG 3: Good Health and Well-being
   • The article focuses on tuberculosis (TB), a major global health issue causing millions of infections and deaths annually.
   • It discusses the discovery of a new compound, JNJ-6640, aimed at improving TB treatment, directly contributing to health improvement.
2. SDG 9: Industry, Innovation, and Infrastructure
   • The article highlights scientific innovation in drug discovery through collaboration between pharmaceutical companies and research institutions.
   • Development of new drugs and drug candidates reflects advances in scientific research infrastructure.
3. SDG 17: Partnerships for the Goals
   • The article emphasizes collaborative efforts among multiple partners, including Johnson & Johnson, London School of Hygiene and Tropical Medicine, and the Gates Foundation.
   • This cooperation exemplifies global partnerships to combat infectious diseases.

2. Specific Targets Under Those SDGs Identified Based on the Article’s Content

1. SDG 3: Good Health and Well-being
   • Target 3.3: By 2030, end the epidemics of AIDS, tuberculosis, malaria, and neglected tropical diseases and combat hepatitis, water-borne diseases, and other communicable diseases.
   • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases that primarily affect developing countries.
2. SDG 9: Industry, Innovation, and Infrastructure
   • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors, and encourage innovation.
3. SDG 17: Partnerships for the Goals
   • Target 17.6: Enhance North-South, South-South, and triangular regional and international cooperation on and access to science, technology, and innovation.
   • Target 17.7: Promote the development, transfer, dissemination, and diffusion of environmentally sound technologies to developing countries.

3. Indicators Mentioned or Implied in the Article to Measure Progress Towards the Identified Targets

1. Indicator for Target 3.3:
   • Incidence rate of tuberculosis (number of new TB cases per year) – the article states 10.8 million people contracted TB in 2023.
   • Tuberculosis mortality rate – the article mentions 1.25 million deaths due to TB in 2023.
2. Indicator for Target 3.b:
   • Number of new TB drugs developed and approved – the article references the last FDA-approved TB drug (pretomanid in 2019) and the new compound JNJ-6640 under development.
   • Progress in clinical trials and drug efficacy against TB strains.
3. Indicator for Target 9.5:
   • Number of scientific collaborations and partnerships in drug discovery.
   • Number of innovative compounds developed targeting TB.
4. Indicator for Targets 17.6 and 17.7:
   • Number and extent of international partnerships supporting TB research (e.g., Gates Foundation’s Tuberculosis Drug Accelerator).
   • Access to new technologies and knowledge sharing among countries and institutions.

4. Table: SDGs, Targets and Indicators

Source: cen.acs.org