Recent Patents on Endocrine, Metabolic & Immune Drug Discovery - Volume 6, Issue 3, 2012

The central objective in treating patients with Parkinson's disease (PD) is two-fold (i) to increase the striatal dopamine content and (ii) to prevent further degeneration of the surviving dopaminergic neurons in the substantia nigra region of the ventral midbrain. Most of the current PD drugs contribute to the former and provide symptomatic relief. Although compounds such as Levodopa (L-DOPA) improve the striatal dopamine content, their long-term usage is associated with progressive decrease in drug response, motor fluctuations, dyskinesias and drug-induced toxicity. In addition, these drugs fail to prevent the progression of the degenerative process. This has shifted the focus onto alternative therapeutic approaches involving natural products that could provide independent therapy or offer neuroprotective support to the existing drugs. The current review describes the neuroprotective and therapeutic utility of such natural products including herbal extracts, phytochemicals and bioactive ingredients from other natural sources either in isolation or in combination, with potential application in PD, highlighting the relevant patents.

In the present study, we evaluated recent patents that describe products or methods able to down-regulate the pro-inflammatory action of HMGB-1, also called as amphoterin. High Mobility Group Box-1 (HMGB-1) has been implicated in the pathogenesis of inflammatory diseases. HMGB-1 has been proposed to be a crucial mediator in the pathogenesis of many diseases including sepsis, arthritis, cancer, autoimmunity diseases and diabetes. It has been suggested that HMGB-1 itself can signal through RAGEs (receptor for advanced glycation end products) and through the Toll-Like Receptors TLR2 and TLR4. Activation of these receptors results ultimately in the activation of Nuclear Factor-kappaB (NFkappaB), inducing the up-regulation of leukocyte adhesion molecules, production of pro-inflammatory cytokines and angiogenic factors in both hematopoietic and endothelial cells, thereby promoting inflammation. There are several patents proposed for controlling the production, secretion and neutralization of HMGB-1 and consequently the inflammatory process. We have divided the patents in six groups based on mechanism of action. The group 1 is associated with inhibition of HMGB-1 using anti-HMGB-1 antibodies; group 2: inhibition of HMGB-1 releases from the nucleus into the extracellular space; group 3: HMGB-A box as a competitive antagonist of HMGB-1; group 4: blockage of RAGE-HMGB-1 signaling using RAGE antagonists; group 5: blockage of TLR-HMGB-1 signaling using anti-TLR2 antibodies and group 6: other molecules that modulate HMGB-1 activity using e.g. human soluble thrombomodulin. The mechanism of HMGB-1 action, its role and efficiency of each group of patents proposed for controlling inflammation are discussed.

Thrombin activatable fibrinolysis inhibitor (TAFI) is a zymogene that potently inhibits fibrinolysis through the removal of the carboxy-terminal lysine and arginine residues from partially degraded fibrin polymers. In addition, TAFI has a suppressor effect on conversion of inactive plasminogen to plasmin. Since impaired fibrinolysis is a very well established risk factor for cardiovascular morbidity and mortality, understanding the role of TAFI in cardiovascular disorders, insulin resistance, diabetes and other endocrine problems may hold promise for improving management of these diseases. This paper includes a review of current evidence on TAFI pathway and its alteration in endocrine and cardiovascular disorders and relevant patents.

Endometriosis is an inflammatory disease characterized by the presence of endometrial glandular epithelial and stromal cells growing in the extra-uterine environment. The disease affects: ovarian function, oocyte quality, embryo development and implantation, and uterine function resulting in infertility or spontaneous pregnancy loss. Even though the world’s prevalence is above 10 %, an effective treatment has not yet been found. New pharmacological approaches have been designed and patented that could serve as future therapies for this disease.

Glaucoma is an eye condition mainly developed from an excessive intraocular pressure. The condition tends to be inherited and may not show up until later in life. The increased pressure, can damage the optic nerve, provoking loss of vision. Without treatment, glaucoma can cause blindness within a few years; consequently glaucoma has to be diagnosed before long-term visual loss occurs. If it is diagnosed and treated early, the disease can be controlled. Usually, the patient does not notice any early symptoms or pain from this increased pressure, so the early diagnosis is problematic. Over half of the patients with glaucoma are unaware they have this blinding disease and by the time they are diagnosed, they already have irreversibly lost approximately 30-50% of their retinal ganglion cells. Glaucoma diagnosis is currently based on specific signs of the disease, characteristic optic nerve head changes and visual field loss. Thus, improved methods for early diagnosis of glaucoma are needed. Molecular genetics are valuable for the understanding the pathophysiology and cure of glaucoma, but still are not widely used for its diagnosis. Genetic studies on glaucoma have revealed many genes and chromosomal loci associated to glaucoma. Consequently, a better understanding of the molecular mechanisms underlying glaucoma is required to obtain early diagnosis and avoid potential disease progression. In this article, we revise the patents and the corresponding literature on the latest developments and approaches in glaucoma diagnosis, using mainly molecular genetics.

The hypothalamus and posterior pituitary form a complex neurohumoral system playing a key role in maintaining body fluid homeostasis and reproductive function. We review the pathophysiology mechanisms of posterior pituitary hormones and their implications, beyond water balance and delivery, in social functioning, pair bonding and affiliative behavior. Actual and future treatments for neurohypophysis related disorders are also discussed, particularly focusing on the development of new therapeutic compounds and patents.

Microtubules (MTs) are ubiquitous eukaryotic proteinaceous filaments showing a hollow cylindrical structure. MTs are composed of α-β-tubulin heterodimers arranged in linear protofilaments. MTs have a significant electric dipolar moment along their axes, which makes them capable of being aligned parallel to the applied electromagnetic field direction. Tubulin heterodimers were purified from rat brains. MTs were obtained by polymerization in vitro. Samples of microtubules adsorbed under and without electromagnetic fields with 500 Hz frequency. Our results demonstrate the effect of electromagnetic field with 500 Hz frequency to increase the polymerization of MTs. Some relevant patents are also outlined in this article.

The patents annotated in this section have been selected from various patent databases. These recent patents are relevant to the articles published in this journal issue, categorized by therapeutic areas/targets & therapeutic agents related to endocrine, metabolic and immune drug discovery.....