Utilization of ATP administration for the treatment of cancer and AIDS

Abstract

Preclinical animal studies as well as recent clinical Phase I studies have demonstrated that organ, total blood (red blood cells) and blood plasma compartment pools (steady state levels) of adenosine 5'-triphosphate can be readily increased by administration of adenine nucleotides. The achievement of elevated ATP pools yields puriner-gic activation thus affecting a whole spectrum of physiological activities which are regulated by ATP interacting with P2 receptors and adenosine, the catabolic product of ATP, interacting with P1/A adenosine receptors. The anticancer activities of ATP which have been demonstrated in preclinical murine models and in initial human trials consist of cytostatic and cytotoxic effects on the tumour, anticachexia effects and improvement of liver and kidney functions, modulation of blood flow, anti-anaemia effects, analgesic activities, improvement in motor functions and performance status, improvements in oxygen delivery to peripheral sites, enhancement of superoxide anion (O2) production by phagocytic cells and antithrombotic and profibrinolytic activities. The extensive data regarding the activation of ATP and adenosine receptors along with a variety of recent human and animal studies indicate that ATP administration is likely to yield significant clinical benefits in patients with advanced HIV disease/AIDS. The physiological parameters which are expected to be affected after administration of ATP to people with advanced AIDS are improvements (immune reconstitution) of T-cell proliferation and cytctoxicity, down-regulation of TNF-α and IL-6 synthesis, improvements in gut absorptive capacity and in the integrity of the intestinal mucosa, reversal of cachexia-wasting by expansions of organ ATP pools and its mediated inhibition of hypermetabolism, positive effects on organ function and cytoprotection during administration of high-dose cytotoxic antiviral agents.