Recent Patents on Endocrine, Metabolic & Immune Drug Discovery - Volume 4, Issue 1, 2010

Immunoisolation is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. During the past decades a number of different approaches of immunoisolation have been described. The approaches include (i) intravascular devices, which are anatomized to the vascular system, (ii) extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites, and (iii) extravascular microcapsules. Many reviews describing the advantages and pitfalls of the different approaches of immunoisolation have been described during recent years. Almost none of these reviews however describe the technical advances and (pre)clinical results described in the numerous patents on the subject. Therefore this review presents the recent novelties described in patents related to immunoisolation of tissue.

Medullary thyroid carcinoma (MTC) is a rare tumor arising from neural crest-derived parafollicular C cells. Metastatic MTC patients are incurable because the cancer does not respond to radiotherapy or chemotherapy. The elucidation over the past two decades of multiple genetic abnormalities in MTC has provided specific targets for therapy. The identification of activating mutations of the RET tyrosine kinase receptor (TKR) in both hereditary and sporadic MTC makes this malignancy an excellent model to examine the effect of a group of small organic molecule tyrosine kinase inhibitors (TKIs) for treatment of metastatic MTC. Clinical trials with several TKIs targeting RET and other TKRs have shown positive results with generally tolerable toxicity. Approximately one-third to one-half of MTC patients have a reduction in tumor size up to 50%, with the longest treatment duration of approximately four years. The most common treatment-related toxicities are rash, nausea and diarrhea. Despite promising initial results these studies are in their early stages; however, the possibility of testing the sensitivity of primary MTC cells from each subject to different TKIs could increase the effectiveness of the treatment. A brief outline on current patents that are the focus on the treatment of Thyroid Cancer has also been provided in this review.

Osteoporosis, a common disease today, has serious impacts on both patients and society, because prognosis can be complicated and therapy costly. It is therefore important to identify risk factors for osteoporosis to ensure the prevention and early detection. Adjustment of confounding factors is important for accurate evaluation of risk factors. In societies with long average life spans, the number of people with multiple chronic diseases has increased in recent years, resulting in many reports of secondary osteoporosis caused by medication. In this report, we aim to review the possibility that antihypertensive drugs impact osteoporosis by investigating epidemiological research results. As a search strategy, PubMed has been searched using the keywords “osteoporosis,” “bone mineral density,” “fracture,” “hypertension,” and “drug-induced” in April 2009. The abstracts have been screened and epidemiological studies have been included. In addition, the authors have also screened reference lists of relevant papers. The results of the present review seem to suggest the possibility that thiazide diuretics and β-blockers have positive effects on bone, whereas loop diuretics appear to have adverse effects. In examining effects of drugs on bone, detailed review is necessary on the duration, time since suspension of use, and quantity of drugs used. This review summarizes the impact of antihypertensive drug on bone mineral density and recent patents for the treatment of osteoporosis.

Osteoporosis is a major public health problem affecting all countries and giving rise to fractures. The World Health Organization (WHO) published a set of diagnostic criteria to define osteoporosis in postmenopausal Caucasian women, using bone mineral density (BMD) values measured by dual energy X-ray absorptiometry (DXA). Currently, measurement of BMD by DXA (g/cm2) has been the standard method for diagnosing osteoporosis, in addition to assessing fracture risk and therapeutic effects. Quantitative computed tomography (QCT) can quantify volumetric BMD (mg/cm3), and cancellous bone can be measured independently of surrounding cortical bone and aortic calcification. Recently, quantitative ultrasound (QUS) is emerging as a relatively low-cost and readily accessible alternative means to identify osteoporosis and evaluate fracture risk. More recently, finite element (FE) method based on data from computed tomography (CT) has been used to assess bone strength, fracture risk, and therapeutic effects on osteoporosis. In this review, recent patents and methods for assessing bone mineral density, bone strength, fracture risk and therapeutic effects on osteoporosis are outlined.

Recent research interest has focused on the role of vaccination in preventing type 1 diabetes in high-risk patients. High-risk subjects are identified on the basis of genetic and antibody markers. While no single intervention strategy has been demonstrated to have universal efficacy, this review focuses on the developments and recent patents in this field.

Obesity is at an epidemic level. All patients who are overweight and obese should be treated with diet, exercise, behavioral therapy or a combination thereof; however, these therapies may not be adequate for a number of patients. Pharmacotherapy should be considered for patients who are obese, are overweight with cardiovascular risk factors, or have failed standard therapy. Several medications, such as phentermine and diethylpropion for short-term treatment as well as sibutramine and orlistat for long-term treatment, are currently available. There are also off-label uses of other medications such as antidepressants, anticonvulsants, and anti-diabetic medications, for the management of obesity. All of these medications provide additional weight loss when used as an adjunct to the standard therapy of lifestyle modification. The objective of this review is to summarize different patents and new approaches in the treatment of obesity.

Cell microencapsulation holds promise for the treatment of many diseases by the continuous delivery of therapeutic products. The complexity of many diseases, such as neurological and metabolic disorders needs the generation of new drugs and especially new pathways to deliver the drug at proper concentration and into the correct localization. One hopeful technology is the developing of new biomaterial components with the capacity to envelope drugs, cells or tissues, being able to distribute the therapy; and at the same time, to be isolated from the immune system. Microcapsules technology has this capacity: releasing the necessary drug in a precise location with a long-term efficacy, and keeping the grafts isolated from the immune system. The objective of this review is to summarize the last patents and news related with microencapsulation technology, and the possible therapeutic applications in different disorders.

Dendritic Cells (DC) play a pivotal role in the initiation of T-cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. The interaction of T cell with DC is crucial for directing T cell differentiation towards the Th1, Th2 or Th17 type, and several factors determining the direction of the T cell polarization. IL-12 plays a central role in the immune system, not only by augmenting the cytotoxic activity of T cells and NK cells and regulating IFN-γ production, but also by the capacity of IL-12 to promote the development of Th1. Some plant-derived terpenes regulate differentiation of DC from human monocytes. Terpene compounds-primed DC enhances the differentiation of naive T cell towards the Th1 type, which is dependent on IL-12 secretion. Some patents on terpene compounds, which may lead to the development of effective immunotherapy for cancer, are also discussed in the review.

Obesity is currently one of the greatest health problems in industrialized countries, and yet there is no reliable method to fight this pandemic. Bariatric surgery is the most effective method to reduce body weight in morbidly obese patients, suggesting that gastrointestinal tract derived signals are crucial for energy balance regulation. This would indicate that homeostatic mechanisms responsible for body weight maintenance, involving the brain-gut axis are critical for obesity prevention and development. Several descriptive studies have proven the presence of gastric endogenous systems that modulate energetic balance (ghrelin - obestatin system and endocannabinoid system); however, these systems and their interactions are still not well known. The present review describes recent investigations that support the role of the stomach as an energy balance regulator which exerts its effects over known and probably unknown gastrointestinal systems. Additionally, information covering new gastrointestinal derived peptides patents for obesity treatment is provided as well.

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.