Recent Patents on Endocrine, Metabolic & Immune Drug Discovery - Volume 8, Issue 1, 2014

This article reviews the more recent patents in three kinds of therapeutic strategies using the application of visible light to irradiate photosensible substances (PSs) of different natures. The light-activation of these PSs is directly responsible for the desired therapeutic effects. This group of light therapies includes photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). Therapeutic mechanisms triggered by the activation of the PSs depend basically (though not exclusively) on the release of reactive oxygen species (ROS) and the activation of immune responses (PDT and PIT) or the local generation of heat (PTT). The main difference between PIT and PDT is that in PIT, monoclonal antibodies (MABs) are associated to PSs to improve the selective binding of the PSs to the target tissues. All these therapeutic strategies offer the possibility of destroying tumor tissue without damaging the surrounding healthy tissue, which is not achievable with chemotherapy or radiotherapy. PDT is also used as an alternative or adjuvant antimicrobial therapy together with the traditional antibiotic therapy since these organisms are unlikely to develop resistance to the ROS induced by PDT. Furthermore, PDT also induces an immune response against bacterial pathogens. The current challenge in PDT, PIT and PTT is to obtain the highest level of selectivity to act on targeted sick tissues with the minimum effects on the surrounding healthy tissue. The development of new PSs with high affinity for specific tissues, new PSs- MABs conjugates to bind to specific kinds of tumors, and new light-sensible nanoparticles with low toxicity, will increase the clinical utility of these therapies.

Lysosomal storage diseases (LSDs) are a group of rare genetic multisystemic disorders, resulting in deficient lysosomal activity. These pathologies are characterized by progressive accumulation of storage material within the lysosomes, ultimately leading to organ dysfunctions. LSDs patient’s clinical outcomes have significantly improved, since the advent of enzyme replacement therapy (ERT). ERT is approved worldwide for 6 LSDs: Gaucher disease, Fabry disease, Mucopolysaccharidosis types I, II, and VI, and Pompe disease. The efficacy and safety of ERT for LSDs has been confirmed by extensive clinical trials, however therapy with infused protein is life-long and disease progression is still observed in treated patients. Obstacles to successful ERT, such as immune reactions against the infused enzyme, miss-targeting of recombinant enzymes, and difficult delivery to crucial tissues (i.e. brain and bone), determine the need for further research, in order to ameliorate therapeutic strategies. Viral gene therapy, stem cell based therapy, pharmacological chaperones and could be considered essential tools for future improvement of recombinant enzyme trafficking and targeting. This review will discuss recent patents and new strategic approaches for enzyme delivery to highlight the most relevant aspects, concerning next generation LSDs treatment.

Dendritic cell (DC) immunotherapy has been used to treat various types of tumors. Although it is already in use in clinical practice, the mechanisms through which it acts need clarification. In addition, the processes used to obtain DCs need to be improved so that more effective treatments can be offered. In this article, we present an update on the application of DC immunotherapy and the patents involved in the process.

Hyperprolactinemia is an unwanted adverse effect present in several typical and atypical antipsychotics. Aripiprazole is a drug with partial agonist activity at the level of dopamine receptors D2, which may be effective for antipsychotic- induced hyperprolactinemia. Therefore, we analyzed the literature concerning the treatment of antipsychoticinduced hyperprolactinemia with aripiprazole by updating a previous paper written on the same topic. More recent studies were reviewed. They showed that there are two options for the treatment of antipsychotic-induced hyperprolactinemia with aripiprazole. The safest strategy may require the addition of aripiprazole to ongoing treatments, in the case patients had previously responded to antipsychotic drugs and then developed hyperprolactinemia. However, it is advisable to monitor the patients in case relapses and/or side effect, although rare, might occur. Switching drugs should be considered when a patient does not appear to be responding to the previous antipsychotic, thus developing hyperprolactinemia. A cross-taper switch should always be considered, but the risk of a relapse in the disorder may occur more frequently and the patients should be closely monitored. However, limitations must be considered and further studies are needed to definitely elucidate this important issue. Some relevant patents are also described in this review.

Thyroid dysfunction and psychiatric disorders share a bidirectional relation. Thyroid hormones have been found to affect the central nervous system both structurally and functionally. Conventional antidepressant drug therapy is characterized by a delayed and at times suboptimal response. Various strategies have been devised in order to circumvent this limitation. L- Thyroxine has been used as both acceleration therapy and augmentation therapy as adjuvant therapy with antidepressants. The hormone has also been used as monotherapy, both in prevention and management of depression. The potential use of thyroid hormone as an adjunct therapy in management of euthyroid depression and relevant patents has been discussed.

In the recent years, a large number of potential biomarkers for Chronic Obstructive Pulmonary Disease (COPD) have been described. One of the important biomarkers is Surfactant Protein D (SPD) since serum SPD levels have been associated with lung function or health status in patients with severe COPD. Several interesting evidences of the protein and gene polymorphisms have been described. The present review highlights the current literature, recent patents and, future prospects of this important collection.

In the management and treatment of osteoporosis, the target is to assess fracture risk and the end-point is to prevent fractures. Traditionally, measurement of bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) 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, and cancellous bone can be measured independently of surrounding cortical bone and aortic calcification. Hip structure analysis (HSA) is a method using the DXA scan image and provides useful data for assessing hip fracture risk. Recently, new tools to assess osteoporosis and fracture risk have been developed. One of the recent advances has been the development of the FRAX (Fracture Risk Assessment Tool), which is helpful in conveying fracture risk to patients and providing treatment guidance to clinicians. Another advance is the finite element (FE) method based on data from computed tomography (CT), which is useful for assessing bone strength, fracture risk, and therapeutic effects on osteoporosis. In selecting the most appropriate drug for osteoporosis treatment, assessment by bone metabolic markers is an important factor. In this review, recent patents for assessing osteoporosis and fracture risk are discussed.

Metabolic syndrome (MetS) is a syndrome that involves at least three disorders dyslipidemia, insulin resistance, obesity and/or hypertension. MetS has been associated with several chronic diseases in the adulthood; however, in the recent years, the syndrome was redefined in children. Girls with early menarche and asthma, and children with MetS and asthma that reach adulthood appear to have higher risk to develop severe or difficult to control asthma and a higher probability to suffer cardiovascular diseases. It has been proposed that patients with MetS and endocrinological disorders should be considered a different entity in which pharmacologic treatment should be adjusted according to the individual. Recent patents on the field have addressed new issues on how endocrine control should be managed along with asthma therapeutics. In the near future, new approaches should decrease the high morbidity and mortality associated to these types of patients.

Diabetes is a chronic metabolic disorder in humans constituting a major health concern today whose prevalence has continuously increased worldwide over the past few decades. Production of reactive oxygen species (ROS) and disturbed capacity of antioxidant defense in diabetic subjects have been reported. It has been suggested that enhanced production of free radicals and oxidative stress is the central event for the development of diabetic complications. Antioxidants can play an important role in the improvement of diabetes. There are many reports on the effects of antioxidants in the management of diabetes. This study aimed at evaluating the effect of antioxidant extract and purified sweet and sour Cherries on hyperglycemia, microalbumin and creatinine level in alloxan-induced diabetic rats. Thirty six adult Male Wistar rats were divided equally into six groups. Diabetes was induced in the rats by an intraperitoneal injection with 120 mg/kg body weight of alloxan. Oral administration of cherry extract at a concentration of 200 mg/kg body weight for 30 days significantly reduced the levels of blood glucose, and urinary microalbumin. Also an increase in the creatinine secretion level in urine was observed in the diabetic rats treated with the cherry extract as compared to untreated diabetic rats. In this paper, the most recent patent on the identification and treatment of diabetes is used. In conclusion, cherry antioxidant extract proved to have a beneficial effect on the diabetic rats in this study. In light of these advantageous results, it is advisable to broaden the scale of use of sweet and sour cherries extract in a trial to alleviate the adverse effects of diabetes.