Preventing and Correcting Communicable and Non-Communicable Chronic Disease via Amlexanox – Dual ‘No-Nonsense’ and Inflammatory Axis Targeting

Abstract

In this sequel article on Amlexanox I investigate the multi-tasking potential for this drug, a recently discovered readthrough agent with immune-modulatory properties, for management of a wide range of human diseases including ageing modeled as a disease. The focus is not only on correction or disease rescue, but also on early prevention through use of Amlexanox prophylaxis. The concept of readthrough of nonsense mutations is further explored and correlation of nonsense mutation with cancer spread and stage is examined. Many other prevalent disease processes are examined in the light of nonsense-mediated causation, for example, intellectual disability and ageing. A primary aim of my current investigation is to show that both communicable diseases (related to infections from viral and bacterial agents) as well as non-communicable diseases (such as cancer, diabetes and inherited malformations/dysfunctions) may all form suited targets for Amlexanox therapy. As such, ex vivo and in vitro studies and animal models are discussed with the overall theme being to translate positive findings into the clinic. Clearly, this would have a major benefit with management in many inherited disease states and for infectious diseases. Further, a major benefit can be predicted for acquired chronic conditions too. The long understood property of Amlexanox in immune-modulation is exploited in this analysis. By acting through part-control of the NF-kappaB transcriptional factor-inflammatory axis, Amlexanox is capable of modulating the pathophysiology of such processes as cancer, vascular disease and diabetes with obesity. Moderating the response to pathogen challenge is a focus of attention in this present investigation. This is important insofar as Amlexanox mediates inflammatory-axis regulation and host-pathogen interactions, strongly suggesting that it must be explored in this context. As a result of this, interference with this arm of the innate immune system may well have consequences in terms of exposure to certain infectious agents. Detailed animal model systems as well as formal clinical trials are definitely called for to clarify the longer-term adverse reaction this may produce in the face of pathogen exposure. Amlexanox has been clinically approved for many years and, along with other drugs with similar immune-modulating capacity, appears satisfactory for long-term usage. Therefore, in practical terms, pathogen challenge in such a context may not pose significant threat. Overall, clinical trials are universally called for in order to ascertain the full potential for this old drug presenting with some exciting 'new tricks'. I aim to be able to purposefully 'repurpose' Amlexanox and add this drug into the 'Doctor's bag' as a highly valuable medical adjunct to manage a wide plethora of medical conditions.

Purification and Characterization of the Principal Antimutagenic Bioactive as Ethoxy-Substituted Phylloquinone from Spinach (Spinacea oleracea L.) Based on Evaluation in Models Including Human Lymphoblast TK+/– Cells

“…Quite often living organisms are exposed to various genotoxic agents from industrial sources, biocides (insecticides, herbicides, and pesticides), and natural biotic (viruses, toxigenic microbes including fungi) or abiotic (radiation) sources . This may result in increased DNA damage and subsequent mutations that possibly are translated and manifested in chronic diseases such as atherosclerosis, cardiovascular diseases (CVD), and neoplastic inductions. , Dietary intervention has been postulated to minimize the onset of such diseases mostly due to the occurrence of natural antimutagens. − As per the World Health Organization (WHO), cancer prevention is closely linked to diet, and around one-third of all cancer deaths are preventable …”

Viewing cancer pathophysiology as a lead in understanding cardiac and vascular disease mechanisms

“…These effects in the diabetic disease model are associated with increase in cardiomyocyte cAMP levels and PKA activity and downregulation of tumour suppressor PTEN level alongside downstream oncogenic prosurvival cascade activation. Amlexanox, an agent employed for decades as an immunemodulator [6], via targeting NF-kappa B noncanonical kinases TBK1 and ikkepsilon, reduces activation of the adipocyte phosphodiesterase, PDE3B. Thus Amlexanox therapy is capable in the animal model to restore PKA signaling and augment cAMP in adipocytes [77] similar to the infarct sparing cardiomyocyte mechanism in diabetes [76].…”

“…A literature search was performed using the PubMed database through use of key words joined via the Boolean operator 'and' as I have detailed recently [6]. The means of producing novel concepts by bridging seemingly unrelated knowledge fields is known as 'literature-based discovery' (LBD).…”

“…Obesity and diabetes, important co-morbities of cardiac and vascular diseases, are related to 'metinflammation' , or metabolic inflammation, resulting in insulin resistance [61]. Targeting inflammatory response via modulating the NFkappa B signaling axis-a central player-by such newly 'repurposed' immune modulatory agents as Amlexanox may hold significant promise for a multitude of inflammatory-related conditions such as atheroma [6]. Interestingly, the link between cancer and inflammation, and NF-kappa B and atheroma has been strongly underlined with ox-LDL and its receptor LOX-1 [62].…”

“…As I have detailed [5,6], inflammation is a major mechanistic common linkage between many conditions such as atheroma/ vascular disease, cardiac disease, cancer and neurological disease. Obesity and diabetes, important co-morbities of cardiac and vascular diseases, are related to 'metinflammation' , or metabolic inflammation, resulting in insulin resistance [61].…”