Recent Patents on Endocrine, Metabolic & Immune Drug Discovery - Volume 7, Issue 1, 2013

Despite decades of research, current cancer therapies extend survival but often do not actually cure the disease. Immune cell based therapy is described here that can eliminate tumor cells without the toxicity associated with chemotherapy or allogeneic bone marrow transplant (BMT). Allogeneic BMT has beneficial graft vs. tumor (GVT) effects but accompanied by the undesirable graft vs. host disease (GVHD). The mechanism described here relates to generating the Mirror Effect™ that elicits a host vs. tumor (HVT) effect along with a non-toxic host vs. graft (HVG) response. The HVT effect generated by inducing the Mirror Effect™ in a host is effective in cancer therapy, as well as other diseases. The patent strategy, employed for successful patent prosecution related to the elucidation of the Mirror Effect™, is also discussed.

Metabolic syndrome (MetS) is characterised by symptoms of obesity, insulin resistance, hypertension, dyslipidemia and diabetes mellitus. The pathophysiological mechanisms involved in MetS are complex and involved dysregulation of many biochemical and physiological regulatory mechanisms of the body. Elevated levels of low density lipoproteins like VLDL, and LDL with reduction of HDL seen in patients with MetS contribute to atherogenic dyslipedemia. Melatonin has been suggested to be effective in improving MetS through its anti-hyperlipidemic action. Melatonin reduced both adiposity, and body weight in experimental animal studies and also attenuated weight gain and obesityinduced metabolic alterations and this effect of melatonin is attributed to its anti-oxidative effects. Melatonin administration has been shown to inhibit insulin release by acting through both MT1 and MT2 melatonin receptors present in pancreatic β-cells. Melatonin also increased insulin sensitivity and glucose tolerance in animals fed with either high fat or high sucrose diet. Melatonin exerts most of its beneficial actions by acting through MT1 and MT2 melatonin receptors present in various tissues of the body and some of the metabolic actions of melatonin have been blocked by melatonin antagonist like luzindole. Ramelteon, the newly available melatonin agonist will also have more promising role in the control of MetS. The numbers of patents are available with regard to treatment of MetS. Drug related to antidepressant fluoxetine is used for treatment of MetS (US Patent No. 2008001400450). Anti-oxidants like S-adenosyl-methionine, Vitamin E, and Vitamin C have been found beneficial in treating MetS (US Patent No. 8063024). Melatonin being a powerful Antioxidant will have a promising role in treating patients with metabolic syndrome.

The increase of allergic diseases has accompanied the global population growth and the major challenge is to reduce morbidity. The currently available treatments present limitations regarding efficacy and safety. Hence, patients with chronic allergic conditions seek alternatives to achieve better control of symptoms. Many natural products have been identified as potential anti-allergic agents. In addition, plant formulations have demonstrated, in general, to be safe in clinical trials and demonstrate additional effects along with Western medicines such as synergism and modulation of the immune system. It is known that plants represent a source of new therapeutic agents and some of them have shown mechanisms of action similar to synthetic agents. However, in general, herbs and their combination are patented mainly by Asian countries to be used in food and drinks or cosmetics and dietary supplements and the anti-allergic mechanisms of action are not yet fully elucidated. In this review, we highlight relevant patent and studies with cultivated plants, plant formulations, and secondary metabolites that have been evaluated with respect to its anti-allergic potential.

Uncontrolled diabetic patients often develop diabetic nephropathy (DN). Since, it involves different molecular pathways, such as polyol pathway, protein kinase - C (PKC) activation, inflammatory and oxidative stress etc., and so multi-targeted drugs would be required for its management. Although, combination therapies with various conventional medicines are already in use, but herbal preparations are being preferred as adjuvant therapy, because of their multi targeted drug action due to the presence of natural cocktail of various secondary metabolites. This review describes pathogenesis of DN, possible approaches for its management and information about recent patents and bio-products, which are in pipe line of drug development.

A growing body of evidence has implicated the plasminogen activating system in various aspects of neurophysiology and pathophysiology. In ischemic stroke, blood-brain barrier (BBB) regulations, typically involving matrix metalloproteinases (MMPs), inhibitors tissue inhibitors of metalloproteinases (TIMPs) and the low density lipoprotein receptor- related protein/alpha 2-macroglobulin receptor (LRPs) as mediators became interesting since tissue plasminogen activator (tPA)-related BBB breakdown with risk of secondary hemorrhage was considered to involve these mediators too. The mechanism by which tPA implements its actions within the central nervous system (CNS) has been the topic of much controversy. Binding of plasminogen to surfaces is of crucial importance in regulating the function of this system. tPA can modulate permeability of the neurovascular unit in physiological conditions and pathological events exacerbating injury in ischemic stroke, vascular dementia, traumatic brain injury or neurotoxic events. The plasminogen activating enzyme system is widely appreciated for its role in fibrinolysis and thrombolysis and in other areas related to remodelling of the extracellular matrix. However, this enzyme system also has a major impact in the central nervous system under pathological circumstances. The aim of this review is to revise the last patents and news to understand the mechanism by which t-PA modulates BBB permeability.

A 40-year-old female patient with bipolar disorder and premenstrual dysphoric disorder did not present any physical evidence of virilization, treated with quetiapine and lithium carbonate. Laboratory testing showed evidence of hyperandrogenism (Testosterone levels 88.5ng/dL). After control, testosterone levels were normal (free testosterone 0.20 pg/ml, total testosterone 27.90ng/dl), as free thyroxine levels decreased (T4 0.83ng/dl) and increased progesterone levels (progesterone 3.80ng/ml). We consider an association between increased androgenic hormone levels in women, quetiapine and lithium carbonate treatment as well as the presence of an affective disorder and premenstrual dysphoric disorder. Some relevant patents are also outlined in this review.