The World Health Organization grossly classifies the various types of astrocytomas using a grade system with grade IV gliomas having the worst prognosis. Oncolytic virus therapy is a novel treatment option for GBM patients. Several patents describe various oncolytic viruses used in preclinical and clinical trials to evaluate safety and efficacy. These viruses are natural or genetically engineered from different viruses such as HSV-1, Adenovirus, Reovirus, and New Castle Disease Virus. While several anecdotal studies have indicated therapeutic advantage, recent clinical trials have revealed the safety of their usage, but demonstration of significant efficacy remains to be established. Oncolytic viruses are being redesigned with an interest in combating the tumor microenvironment in addition to defeating the cancerous cells. Several patents describe the inclusion of tumor microenvironment modulating genes within the viral backbone and in particular those which attack the tumor angiotome. The very innovative approaches being used to improve therapeutic efficacy include: design of viruses which can express cytokines to activate a systemic antitumor immune response, inclusion of angiostatic genes to combat tumor vasculature, and also enzymes capable of digesting tumor extra cellular matrix (ECM) to enhance viral spread through solid tumors. As increasingly more novel viruses are being tested and patented, the future battle against glioma looks promising.
Migraine is a painful, sometimes debilitating disorder, which is frequently associated with various neurological symptoms. Its prevalence in the population is higher than that of any other neurological disorders, thus the burden of this disease on society is considerable. Although the introduction of triptans nearly two decades ago revolutionized the treatment of the disease there is still a huge unmet need regarding drugs with better properties. Formerly, migraine therapy primarily aimed at treating the pathological alterations of meningeal blood vessels that are thought to directly initiate a migraine headache attack. By now, it has been increasingly recognized by drug companies that abnormal neural function may be more important in the development of the disease and also in triggering an attack. Migraine is associated with an increased neuronal excitability and episodes of cortical spreading depression. Understanding the molecular mechanisms underlying the abnormal functioning of over-activated neuronal circuits may help to identify novel anti-migraine drug targets. Besides a general description of the pathophysiology and pharmacotherapy of migraine this review paper aims at discussing the possible drug targets through which migraine-related hyperexcitability and over-excitation can be attenuated. It will be shown how these new ideas appear in the recent patent literature.
Alzheimers disease (AD) is the most prevalent neurological disease with dementia. AD-related dementia is caused by death and dysfunction of neurons involved in cognitive function. It has been generally believed that increased levels of toxic amyloid-betas (Aβs) are linked to the occurrence of neuronal death as well as dysfunction (Aβ cascade theory). Consequently, lowering levels of toxic Aβs in the brain is considered to be central for therapy of AD. Multiple drug candidates based on this therapeutic strategy have been developed and are being vigorously developed. Some clinical studies have indicated that this strategy is effective. In addition to this theory, Aβ-independent pathomechanisms have been shown to contribute to the progression of AD-related dementia, justifying alternative strategies for AD treatment that are effective against Aβ-independent pathomechanisms. A possible therapeutic strategy belonging to them is to directly suppress AD-related neuronal death and dysfunction. A series of studies indicated that a 24-amino-acid bioactive peptide named Humanin was shown to inhibit neuronal cell death induced by enforced expression of familial AD-related genes. Humanin also protected neurons from being killed by toxic Aβs in vitro. In addition, neuronal dysfunction-associated dementia of mice caused by muscarinic receptor antagonists and intracranially injected toxic Aβs was ameliorated by Humanin therapy. Multiple studies have indicated the existence of a putative specific Humanin receptor on the cell membrane. These results together suggest that an endogenous AD-related humoral factor(s) may inhibit the progression of AD-related dementia by inhibiting both neuronal cell death and dysfunction in vivo. Malfunction of this self-defense mechanism is also hypothesized to be another etiology or an aggravator of AD. Moreover, from a standpoint of AD therapy, stimulation of the AD defense mechanism by a potent Humanin derivative is a promising alternative strategy for AD treatment. The present patents cover Humanin and the methods of its clinical usage.
Alzheimers disease (AD), the most common form of dementia, is a degenerative and progressive neurological disorder characterized by deficit in the cholinergic transmission and formation of senile plaques containing β-amyloid protein in the brain. Although complete pathology of the disease has not been fully elucidated yet, there are several treatment strategies for AD treatment. The complexity of AD is also due to involvement of several enzymes through its progression. Therefore, the most important therapeutic approach has emerged as inhibition of acetylcholinesterase (AChE), which is the key enzyme in the breakdown of acetylcholine. Another very attractive approach to lower β-amyloid protein in fibrillar form has been the α- and β-secretase inhibitors. On the other hand, recently, N-methyl-D-aspartate (NMDA) receptor antagonists have become a strong alternative, which has been approved to be effective in treatment of moderate to severe type of AD. Within the past few years, some pharmaceuticals have become available for clinical use; however, none of them have been shown to possess ability to discontinue the disease up to date. Hence, there is obviously a great need for discovery of new drug candidates of natural or synthetic origins for AD treatment. This review will cover AChE-inhibiting pharmaceuticals from plants and their synthetic derivatives including relevant patent literatures which may promise a future hope for AD treatment.
Networks controlling ingestion-related peptides are also known to be the targets and signals for numerous other systems. Yet, their topological properties are still ill understood. The Ingenuity Pathway Analysis (IPA) was employed to represent molecules engaged in feeding as nodes, and the interactions between them as edges. Using extracted molecules as ‘seeds’ for core analysis it was possible to scrutinize some of the complex relationships of sub-networks and the socalled ‘motifs’ well outside the neighborhoods of their classical roles. Contrary to the requirements for modular structure, the orexigenic and anorexigenic neuropeptides do not represent two types of modules. They are densely interconnected. Functional annotations showed that the same molecules are recruited ad-hoc from a larger ‘repository’ and assembled into dynamic networks for executing diverse physiological functions and behaviors. Some molecules clustered in motifs appear as the multipurpose entities for cell-to-cell signaling, organismal development, cellular movement, growth and proliferation, endocrine system development and tissue morphology, etc. that apparently become active in early ontogeny. Based mostly on neuropeptide Y (NPY), my arguments here will focus on the potential benefits of exploring motifs in network controlling ingestion for generating insights for polypharmacy of obesity-related targets and co-morbid disorders. Recent patents describing new NPY receptor antagonists directed to treat obesity and cardiovascular disorders were cited.
Melatonin (N-acetyl-5-methoxytryptamine) is a molecule known to be produced in multiple cells and organs. It acts at the level of the biological clock, the suprachiasmatic nuclei, to modulate their activity, thereby influencing circadian rhythms, and also sleep processes. The clinical application of melatonin in the treatment of human mental disorders is still in its infancy. Until now, melatonin only has been used in psychiatry because of its hypnotic, resynchronizing and antioxidant actions. In this review, we hypothesized that melatonin might play an important role as an adjuvant therapy, in mental disturbances, due to other properties including its anti-inflammatory, antinociceptive, anxiolytic, drug detoxification properties, protective actions against osteoporosis, etc. Complex interactions occur between the brain and the immune system and currently is accepted that psychological and psychiatric illness can compromise immune and hormonal functions. Altered psychological states often influence the susceptibility of an individual to illness or modify the course of the illness and its prognosis. The present review discusses on the advantages of the co-treatment with melatonin and recent patents in three major psychiatric disorders: depression, bipolar syndrome and schizophrenia. The findings suggest new vistas in both the pathophysiology and the pharmacology of mental disorders.
About 6% of men and 18% of women suffer migraine attacks. Migraine can induce a great impact in the quality of life of the patient and the costs of medical care and lost productivity can be also high. There are two therapeutic approaches in the treatment of migraine: preventive therapy and acute treatment of migraine attack. Immediate treatment with selective serotonin [5-HT1B/1T] receptor agonists (so-called triptans) is the first-line option in the acute treatment of moderate-severe migraine attacks. The introduction in early nineties of triptans was a revolution in migraine therapy and evidences about their efficacy are at present irrefutable. At the moment, there are seven marketed molecules: sumatriptan, rizatriptan, zolmitriptan, eletriptan, naratriptan, almotriptan and frovatriptan. Obviously, every molecule has different pharmacokinetic and pharmacodinamic properties and, moreover, some triptans have several formulations: tablets, dissolvable tablets, nasal and injections. The prescription of one of these seven triptans for a specified patient is based in the drug profile: efficacy, safety, pharmacokinetics and pharmacodynamics. Despite there are a lot of published studies using triptans, no clinical trial has analyzed all the molecules at the same time. Other data to take account in the final prescription are clinical characteristics of the migraine attack and patient characteristics: labour aspects, style of life and the patient medical history. We present a state-of-the-art of the triptan selection in treatment of moderate-severe migraine attacks.