Rationale for the design of a novel tool for immunotherapy based on an emulsion of glycosaminoglycan

Abstract

In this article, we describe the rationale behind the design of an innovative immunotherapeutic tool designated imuno TM that is an emulsion of microbial, lowmolecular-weight chondroitin sulfate non-covalently bound to pure phosphatidylcholine with vitamin D 3 intercalated in the ensuing multi-molecular structure. The rationale for this design derives from the decade-old observation that chondroitin sulfate is the active principle responsible for the immune-stimulatory, anti-cancer properties of cartilage extracts and from the more recent observation that a known immunotherapeutic compound, the Gc protein-derived Macrophage Activating Factor (GcMAF), works as an adjuvant similar, in principle, to the incomplete Freund's adjuvant. From these premises, we designed an innovative tool that uses an ultrapure, low-molecular-weight chondroitin sulfate, thus overcoming all limitations associated with blood-derived or animal-derived non-ultrapure extracts, at the same time guaranteeing constant sulfation profile and charge density. This novel form of chondroitin sulfate is non-covalently bound to pure phosphatidylcholine in a self-assembly manner that is coherent with the principles of negentropy. Vitamin D 3 is then intercalated in this structure that resembles protocells made of a phosphatidylcholine bilayer. Such an association reduces the main side effect of vitamin D 3 that is the induction of hypercalcemia, at the same time maximizing its immunotherapeutic potential. In addition, we describe the mechanism of action of this immunotherapeutic tool with particular reference to stimulation of innate immunity through a mechanism shared by adjuvants such as Freund's adjuvant. Finally, we describe an example of a transdermal delivery system and we discuss possible applications.

Use of an Extremely Biodiverse Probiotic and a Supplement Based on Microbial Chondroitin Sulfate is Associated with a Significant Decrease of Serum Free Kappa Light Chains as well as a Trend Toward Normalization of Kappa/Lambda Ratio and of Plasma Cell Bone Marrow Infiltration in a Case of Multiple Myeloma

“…It is tempting to speculate that the wide-range of effects on the immune system deriving from the extreme biodiversity of the probiotic drink assumed by the patient was synergistic with the effects of the supplement based on microbial chondroitin sulfate, vitamin D 3 and ultrapure phosphatidylcholine as they are described in two recent papers (Ruggiero, 2018;Ruggiero and Pacini, 2018). Such a synergism may well be at work at the molecular level, for example by integrating different mechanisms responsible for DNA repair that counteract DNA instability, a common trait of cancer and other conditions.…”

“…Ratio Kappa/Lambda: 187) that was consistent with the severity of the oncohematological disease according to the updated criteria for the diagnosis of multiple myeloma (Rajkumar et al, 2014). Following hospitalization in October 2018, the patient opted for a complementary approach to her condition consisting in consumption of 50 mL, twice a day, of an extremely biodiverse probiotic drink obtained by fermentation of bovine milk and colostrum; in addition, the Medical Doctor supervising the patient, in October 2018 begun administering 0.2 mL per week of a novel immune-modulating supplement based on microbial chondroitin sulfate, vitamin D 3 and ultrapure phosphatidylcholine (Ruggiero, 2018). A laboratory exam performed three months later (January 10, 2019) demonstrated a 95% decrease of serum free Kappa light chains that went from 2,190 mg/L (October 2018) to 119.40 mg/L.…”

Significance of hydrophobic and charged sequence similarities in sodium-bile acid cotransporter and vitamin D-binding protein macrophage activating factor

“…It is worth noticing that neutralization of positively charged residues may represent a strategy that exploits electrostatic interactions between charges on the surface of molecules. Such as strategy may not be limited to proteins; negatively charged glycosaminoglycans such as lowmolecular-weight chrondroitin sulfate (14) might also serve the scope of binding and neutralizing those sequences. Negatively charged residues in proximity and within the NTCP sequence binding preS1 sequence of HBV Fig.…”

Clinical Experience of Integrative Autism treatment with a Novel type of Immunotherapy

“…Therefore, in order to overcome the limitation due to the presence of a molecule-chondroitin sulfate -of animal origin and of heterogeneous molecular weight, we designed a novel immunotherapeutic supplement designated imuno® that is an emulsion of microbial (nonanimal-derived), homogeneous low-molecular-weight chondroitin sulfate non-covalently bound to pure phosphatidylcholine with vitamin D 3 intercalated in the ensuing multi-molecular structure. The rationale for the design of this novel immunotherapeutic tool and its main features are described in detail in a recent paper [16]. One of the major advances is represented by the use of non-animalderived, ultra-pure, homogeneous low-molecular-weight chondroitin sulfate that represents a different chemical moiety as compared with animal-derived high-molecularweight chondroitin sulfate and shows much-improved efficacy and safety profiles [16].…”

“…The rationale for the design of this novel immunotherapeutic tool and its main features are described in detail in a recent paper [16]. One of the major advances is represented by the use of non-animalderived, ultra-pure, homogeneous low-molecular-weight chondroitin sulfate that represents a different chemical moiety as compared with animal-derived high-molecularweight chondroitin sulfate and shows much-improved efficacy and safety profiles [16]. According to the conclusion of our study "design and development of imuno® represents the culminating point of research in the field of glycosaminoglycans begun in the early eighties as well as the result of years of achievements in the field of immunotherapy with particular reference to GcMAF and Rerum" [16].…”