Expert opinion on biological therapy
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Obesity is a global epidemic with important healthcare and financial implications. Most current antiobesity pharmacological therapies are unsatisfactory due to undesirable side effects. Many drugs have been withdrawn due to safety concerns. Maintaining weight loss remains the Achilles' heel of antiobesity therapy. ⋯ Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist, which has a protracted pharmacokinetic profile compared to native GLP-1 while maintaining its biological activity. It induces weight loss by reducing appetite and energy intake. It stimulates insulin release and decreases glucagon secretion in response to hyperglycaemia. Treatment with liraglutide, in addition with diet and exercise, induces sustained mean weight loss of 7.6 kg at 2 years (weight loss induced by orlistat = 5.7 kg, phentermine/topiramate controlled release 15/92 = 10.9 kg). It reduces blood pressure and improves glycaemic control, which has clinically relevant significance on reducing obesity-related morbidity and mortality. Liraglutide is reasonably well tolerated with gastrointestinal side effects being most commonly encountered. Novo Nordisk filed for regulatory approval of liraglutide 3.0 mg for obesity treatment in December 2013.
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Expert Opin Biol Ther · Jul 2014
ReviewBiological therapies in the acute respiratory distress syndrome.
The acute respiratory distress syndrome (ARDS) is characterised by life-threatening respiratory failure requiring mechanical ventilation, and multiple organ failure. It has a mortality of up to 30 - 45% and causes a long-term reduction in quality of life for survivors, with only approximately 50% of survivors able to return to work 12 months after hospital discharge. ⋯ Although understanding of the pathophysiology of ARDS has improved, to date there are no effective pharmacological interventions that target a specific mechanism, with the only potentially effective therapies to date aiming to limit ventilator-associated lung injury. However, we believe that through this improved mechanistic insight and better clinical trial design, there is cautious optimism for the future of biological therapies in ARDS, and expect current and future biological compounds to provide treatment options to clinicians managing this devastating condition.
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Expert Opin Biol Ther · Jul 2014
ReviewAllogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer.
Chimeric antigen (or antibody) receptors (CAR) are fusion proteins typically combining an antibody-derived targeting fragment with signaling domains capable of activating immune cells. Recent clinical trials have shown the tremendous potential of adoptive cell transfer (ACT) of autologous T cells engineered to express a CD19-specific CAR targeting B-cell malignancies. Building on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic cells are now being explored. ⋯ CAR-modified allogeneic cells have the potential to act as universal effector cells, which can be administered to any patient regardless of MHC type. Such universal effector cells could be used as an 'off-the-shelf' cell-mediated treatment for cancer.
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Expert Opin Biol Ther · Jun 2014
ReviewNew developments in exon skipping and splice modulation therapies for neuromuscular diseases.
Antisense oligonucleotide (AON) therapy is a form of treatment for genetic or infectious diseases using small, synthetic DNA-like molecules called AONs. Recent advances in the development of AONs that show improved stability and increased sequence specificity have led to clinical trials for several neuromuscular diseases. Impressive preclinical and clinical data are published regarding the usage of AONs in exon-skipping and splice modulation strategies to increase dystrophin production in Duchenne muscular dystrophy (DMD) and survival of motor neuron (SMN) production in spinal muscular atrophy (SMA). ⋯ The main approach of AON therapy in DMD and SMA is to rescue ('knock up' or increase) target proteins through exon skipping or exon inclusion; conversely, most conventional antisense drugs are designed to knock down (inhibit) the target. Encouraging preclinical data using this 'knock up' approach are also reported to rescue dysferlinopathies, including limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, distal myopathy with anterior tibial onset and Fukuyama congenital muscular dystrophy.
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Expert Opin Biol Ther · May 2014
Sipuleucel-T and immunotherapy in the treatment of prostate cancer.
Immunotherapy represents an emerging modality of treatment utilized in patients with prostate cancer, among various other malignancies. ⋯ The role of immunotherapy in cancer continues to grow and encompass agents with different mechanisms, and ongoing efforts to identify appropriate timing of therapy and patients for use is integral to the management of prostate cancer.