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Patient's own bone-marrow stem cells could treat resistant TB

9 January 2014

Patients' own bone-marrow stromal (stem) cells could be used to treat resistant tuberculosis (TB), according to a preliminary study by an international research team.

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Conventional treatment for multi-drug resistant TB uses a combination of antibiotics which are toxic to patients. In this study, published today in The Lancet Respiratory Medicine, researchers claim using patients' own bone-marrow stromal cells is safe and could help overcome the body's excessive inflammatory response, repair and regenerate inflammation-induced damage to lung tissue, and lead to improved cure rates.

The World Health Organization estimates that in Eastern Europe, Asia, and South Africa 450,000 people have multi-drug resistant TB, and around half of these will fail to respond to existing treatments.   

TB bacteria trigger an inflammatory response in immune cells and surrounding lung tissue that can cause immune dysfunction and tissue damage. Bone-marrow mesenchymal stromal cells (MSCs) are known to migrate to areas of lung injury and inflammation and repair damaged tissue. They also modify the body's immune response and could boost the clearance of TB bacteria.

The current challenges of treating multi-drug resistant TB are not insurmountable... Further evaluation in phase 2 trials is now urgently required to ascertain efficacy.

Professor Alimuddin Zumla (UCL Research Department of Infection)

In this phase 1 safety study, 30 patients with multi-drug resistant or extensively-drug resistant TB aged 21-65 years old receiving standard TB antibiotic treatment were also given an infusion of around 10 million of their own stromal cells. The cells were obtained from the patient's own bone marrow, then cultured into large numbers in the laboratory before being re-transfused into the same patient. 

MSC infusion was generally safe and well tolerated. During the 6 months follow-up, no serious adverse events were recorded. The most common grade 1 or 2 adverse events were high cholesterol levels (14 of 30 patients), nausea (11 patients), and lymphopenia or diarrhoea (10 patients).

Further analyses showed 16 patients treated with MSCs were deemed cured at 18 months compared with only 5 of 30 TB patients with similar disease not treated with MSCs.

Co-author Professor Alimuddin Zumla, Professor of Infectious Diseases and International Health at UCL and a BRC-supported researcher, said: "The results of this novel and exciting study show that the current challenges and difficulties of treating multi-drug resistant TB are not insurmountable, and they bring a unique opportunity with a fresh solution to treat hundreds of thousands of people who die unnecessarily of drug-resistant TB.

"Further evaluation in phase 2 trials is now urgently required to ascertain efficacy and further safety in different geographical regions such as South Africa where multi-drug resistant and extensively-drug resistant TB are rife."

Professor Markus Maeurer from Karolinska University Hospital in Stockholm, who led the research, explained a follow up with more patients is needed to establish the safety and efficacy of MSC therapy: "The procedures for obtaining stromal cells from the patient's own bone marrow are relatively simple, and if successful in phase 2 trials, will provide a viable adjunctive therapy for patients with multi-drug resistant TB not responding to conventional drug treatment or those with severe lung damage."



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