Cell Therapy for Muscular Dystrophy

Muscular dystrophy is a major unmet medical need associated with an inevitable progressive muscle damage and loss of function. Currently, treatment is only symptomatic and supportive. This chapter focuses on cell therapy as a potential treatment approach for muscular dystrophy. Mechanism of action of cell therapy and its ability to alter disease pathology have been discussed. A review of preclinical and clinical studies has been presented with the advantages and shortcomings of various cell types. Rationale for our treatment protocol and experience of treating muscular dystrophy patients has been discussed. Our published results have shown the efficacy of the intrathecal and intramuscular administration of autologous bone marrow mononuclear cells in different types of muscular dystrophy patients. The scores on outcome measures such as 6-minute walk distance, North star ambulatory assessment, Brooke and Vignose scale, Functional independence measure, and manual muscle testing either improved or were maintained suggestive of slowing down disease progression. Efficacy and safety of the treatment was also studied using comparative MRI-MSK and EMG showing decreased fatty infiltration in various muscles post-cellular therapy. Thus, it was found that autologous BMMNC transplantation is a safe and effective treatment option and improves the quality of life of MD patients

In vitro and in vivo anticancer effects of mevalonate pathway modulation on human cancer cells.

BackgroundThe increasing usage of statins (the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) has revealed a number of unexpected beneficial effects, including a reduction in cancer risk.MethodsWe investigated the direct anticancer effects of different statins approved for clinical use on human breast and brain cancer cells. We also explored the effects of statins on cancer cells using in silico simulations.ResultsIn vitro studies showed that cerivastatin, pitavastatin, and fluvastatin were the most potent anti-proliferative, autophagy inducing agents in human cancer cells including stem cell-like primary glioblastoma cell lines. Consistently, pitavastatin was more effective than fluvastatin in inhibiting U87 tumour growth in vivo. Intraperitoneal injection was much better than oral administration in delaying glioblastoma growth. Following statin treatment, tumour cells were rescued by adding mevalonate and geranylgeranyl pyrophosphate. Knockdown of geranylgeranyl pyrophosphate synthetase-1 also induced strong cell autophagy and cell death in vitro and reduced U87 tumour growth in vivo. These data demonstrate that statins main effect is via targeting the mevalonate synthesis pathway in tumour cells.ConclusionsOur study demonstrates the potent anticancer effects of statins. These safe and well-tolerated drugs need to be further investigated as cancer chemotherapeutics in comprehensive clinical studies