A new combined therapy to treat human Tuberculosis (TB)

Every year, around 2 million people die from TB worldwide, which is caused by the airborne bacteria Mycobacterium tuberculosis (Mtb).

Oxford Researchers have discovered a mechanistic link between the rare Niemann-Pick type C (NPC) disease and pathogenic mycobacteria, including Mtb. A combined treatment of SERCA (sarco-endoplasmic reticulum Ca2+-ATPase) antagonist and an inhibitor of glycosphingolipid biosynthesis, which is clinically approved for use in NPC disease, showed clearance of pathogenic mycobacteria. This combined therapeutic represents a new approach for TB treatment that targets the host cell and could, therefore, overcome the development of antibiotic-resistant strains of TB.

A growing need

Tuberculosis (TB) is an infectious illness caused by the airborne bacteria Mycobacterium tuberculosis (Mtb). An incredible one-third of the world’s population is infected with Mtb, and every year 8.6 million people are diagnosed with TB. Around two million people die from the disease, a large number of whom are immune-compromised individuals.

The only approved vaccine, Bacillus Calmette-Guerin (BCG) has limited efficacy, and the emergence of antibiotic-resistant TB strains has reduced the number of therapeutic options available. There is a growing need to develop new TB therapies to prevent and treat the disease.

A surprising combination

Oxford Researchers have discovered that pathogenic mycobacteria, including Mtb, secrete lipids that inhibit the Niemann Pick type C (NPC) pathway, which has important implications for understanding host-pathogen interactions and for developing new therapies to combat TB. Treatment with SERCA (sarco-endoplasmic reticulum Ca2+-ATPase) antagonists combined with an inhibitor of glycosphingolipid biosynthesis was found to promote clearance of pathogenic mycobacteria via a calcium-dependent mechanism.

This is particularly surprising as other classes of an agent known to be useful against NPC disease, such as miglustat, a clinically approved inhibitor of glycosphingolipid biosynthesis for NPC disease, did not enhance mycobacterial clearance by itself.

This new combined therapy provides a new angle to approach TB treatment that targets the host cell and could overcome the development of resistance. Oxford University Innovation has filed a patent application on this invention and would like to speak with parties interested in taking a licence to further develop this therapy for treatment of TB.

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