New bioMedicines beyond Drugs

The interactome complements the genome, transcriptome, and proteome. It describes the network of interactions between proteins (enzymes that catalyze biochemical reactions) and metabolites (small molecules that act as substrates and inputs in these reactions). It can be thought of as the social network of proteins.

In terms of drug development, according to the experience of BioAcyl Corp for more than 2 decades, establishing interaction at the tissue/microenvironment level is optimal to take advantage of top/down and inverse, bottom/top causation in Adaptive Complex Biosystems. Communication at all levels (interactome) balances the emergent properties of the organism as an entity. From a holistic point of view, an emergent event produces its manifestation subliminally, but the manifestation is not determined by the inherent probabilities of its components. These are necessary, but not sufficient, to determine or constitute the manifestations of the whole and to induce change. This ability to induce changes in the homeostatic state is inherent to the context of the organismal entity.

 

This is clear from the downturn that exists in identifying new bioactive molecules using the reductionist and deterministic method that has dominated interventions in clinical practice since the sixteenth century. But it is also clear that such interventions are limited to treating only certain symptoms, or at most an organ, and do not focus on resolving the cause of the disease. The crisis has led to new approaches of systems biology and to visualize the multiple factors that intervene in a disease and the need to direct interventions to multiple factors and a holistic vision of the sick person. The positive development of the "omics" made it possible to generate abundant information that has clarified outlying phenotypic nodes of therapeutic significance, but without achieving the knowledge to find the appropriate interventions and offer integrated, safe, affordable, and effective multi/receptor treatment. Nor, diminishing the patient's resistance to infection (common off-target) in the pursuit of achieving a determined effect. Apart from the difficulty of finding an agent that is capable to interact with the multiple factors affected, it has not been possible to identify a universal modulator of inflammation, safe and effective, despite the consensus on the "trunk" role that the underlying inflammation plays, in multiple diseases.

With the development of advanced topical treatments at BioAcyl Corp., a new form of healing has been discovered that in optimal circumstances can lead to paligenosis, which although triggered by redox signaling, does not depend on inflammation. This creates a direct contrast to the existing quasi-consensus when it comes to healing with the common process of fibrosis or scarring, and which is argued, benefits from inflammation. However, paligenosis uses processes such as autophagy, production of heat shock proteins, response to misfolded proteins, DNA repair, etc. It employs previously unknown repair processes, which are dominated by negative feedback loops through degradation of pro-IL1B and pro-IL18 and post-translational modifications of NLPR3 (phosphorlization and ubiquitinization) that lead to the removal of inflammasome components and that restrain inflammation. In addition, during autophagy dysfunctional mitochondria are digested and the release of reactive oxidation species which activate the inflammasome, decreases.

The fact that this process ends in regeneration after dedifferentiation of adult cells with their subsequent re-entry into the cell division cycle clearly reveals that the intervention must have taken place in multiple nodes of the tissue/microenvironment. In all likelihood, this is a Systems Medicine intervention. Not only, but it is an intervention that modulates inflammation universally and without off-target effects, due to the process' nature of self-degradation. These are 2 unedited findings.

The translation of the intervention to the clinic, and perhaps facilitated by its admirable safety, gives it great therapeutic value and places it in an advanced position to attack the causes of diseases. The solvency of how these innovations can modulate the underlying inflammatory pathobiology in the vast majority of non-communicable diseases (casuistry in humans), leads us to think that validating this technology in its systemic scope is a valuable opportunity to consolidate interventions capable of treating these diseases, without side effects.

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