Bacterial therapy and mitochondrial therapy

Current methods for treatment of cellular and organ pathologies are extremely diverse and constantly evolving, going beyond the use of drugs, based on chemical interaction with biological targets to normalize the functions of the system. Because pharmacological approaches are often untenable, recent strategies in the therapy of different pathological conditions are of particular interest through introducing into the organism of some living system or its components, in particular, bacteria or isolated subcellular structures such as mitochondria. This review describes the most interesting and original examples of therapy using bacteria and mitochondria, which in perspective can dramatically change our views on the principles for the treatment of many diseases. Thus, we analyze such therapeutic effects from the perspective of the similarities between mitochondria and bacteria as the evolutionary ancestors of mitochondria.     

Anti-fungal therapy at the HAART of viral therapy

HIV-positive patients receiving combination therapy (highly active anti-retroviral treatment, HAART) suffer significantly fewer oral infections with the opportunistic fungal pathogen Candida albicans than non-HAART-treated patients. One component of HAART is an inhibitor of the HIV proteinase, the enzyme required for correct processing of retroviral precursor proteins. It would appear that HIV proteinase inhibitors also have a direct effect on one of the key virulence factors of C. albicans, the secreted aspartic proteinases (Saps). This suggests that the reduction in C. albicans infections in HIV-positive patients might not be solely the result of improved immunological status but could also be caused by the HAART treatment directly inhibiting Candida proteinases.     

Gene therapy

Summary A number of techniques are available for insertion of new genetic information into mammalian cells. Some of these have been used successfully for genetic modification of germ line cells and somatic cells of living animals. Some of these techniques may be applicable to treatment of some of the genetic diseases of man, once problems related to the control of expression of introduced genes are solved.     

Cancer therapy

In recent years a growing recognition that molecularly-targeted therapies face formidable obstacles has revived interest in more generic tumor cell phenotypes that could be exploited for therapy. Two recent reports demonstrate that cancer cell survival is critically dependent on the activity of MTH1, a nucleotide pyrophosphatase that converts the oxidized nucleotides 8-oxo-dGTP and 2-OH-dATP to the corresponding monophosphates, thus preventing their incorporation into genomic DNA. Tumor cells frequently overexpress MTH1, probably because malignant transformation creates oxidative stress that renders the nucleotide pool highly vulnerable to oxidation. As a result, MTH1 inhibition in cancer cells results in accumulation and incorporation of 8-oxo-dGTP and 2-OH-dATP into DNA, leading to DNA damage and cell death. This toxic effect is highly cancer cell-specific, as MTH1 is generally dispensable for the survival of normal, untransformed cells. Importantly, MTH1 proves to be a “druggable” enzyme that can be inhibited both by an existing protein kinase inhibitor drug, crizotinib, and by novel compounds identified through screening. Inhibition of MTH1 leading to toxic accumulation of oxidized nucleotides specifically in tumor cells therefore represents an example of a “non-personalised” approach to cancer therapy.     

Oligonucleotide therapy

Rapid progress in oligonucleotide therapeutics has continued over the past year as major programs established in the past four years have grown and begun to be productive. Important advances were reported in the medicinal chemistry of oligonucleotides and in understanding their pharmacodynamic properties. Significant progress was made in understanding the pharmacokinetic and toxicologic properties of first generation analogs, particularly phosphorothioates and one oligonucleotide, ISIS 2105, entered clinical trials. Additionally, combinatorial approaches designed to identify oligonucleotides that may bind to a variety of targets were reported.     

Antithrombotic therapy

Coronary heart disease is the leading cause of death in the US and the industrialized world. Ever since DeWood in 1980 demonstrated that a thrombus was the primary event leading to acute myocardial infarction and that they may subsequently lyse, the mainstay of therapy for the past 25 years has been antithrombotic therapy aimed at coronary thrombosis. There have been numerous advances in the treatment of acute coronary syndrome with antiplatelet, antithrombotic, and fibrinolytic agents that have significantly reduced morbidity and mortality. The role of various pharmaceutical agents in the different phases of acute coronary syndrome is a complex and ever changing field.7.     

Oxygen therapy

Oxygen, properly administered, often is a valuable therapeutic agent in many conditions such as hemorrhage, heart disease, respiratory diseases, anemia, shock, infection with fever and others in which there is direct or indirect interference with normal oxygenation of tissues. In severe heart disease or acute respiratory conditions, administration of oxygen under pressure may be necessary in order to deliver the required amount to the tissues in want. For conditions in which oxygen want is less critical, 50 per cent concentration of the gas in the inspired atmosphere is effective and more easily carried out. Patients with chronic heart disease may be greatly helped by taking oxygen at home under the direction of a physician.