IntroductiontoPoly MVA

An Introduction to Poly-MVA

Poly MVA is the dietary supplement member of the Lipoic Acid/Palladium Complex (LAPd) family of molecules developed by Dr. Merrill Garnett. The picture below is a model of the LAPd structure. It exists as a trimer, associated with thiamine.

Poly-MVA vs Free Radical Scavengers

Poly MVA differs from free radical scavengers (e.g. alipoic acid) since there is no free lipoic acid or palladium. They are irreversibly bound together resulting in a molecule that is both fat and water soluble. Poly MVA is a polymer (liquid crystal) rather than a single molecule. Therefore, the polymer provides a unified redox (accept charge and donate charge) reaction.

SUMMARY -It is a much more effective energy transferring molecule.

Transfer of Cellular Energy

The original family member, DNA Reductase, was named for its ability to shunt electron energy from itself to DNA. By donating electrons DNA can be reduced, and thus oxida- tion, as a result of radiation and carcinogens, can be combated. Why use Palladium? Since it has a common resonance frequency with DNA, electron transfer between the molecules is facilitated. Also, Palladium can be permanentlybound to lipoic acid.

Safety

In order to demonstrate that the LAPd complexes do not cause mutations. Ames Tests were conducted by an independent lab (PHARMAKON USA)andall mutation tester strains were NEGATIVE. Acute toxicity studies (14 days) were conducted both i.v. and orally. Mice were first administered dosages as high as 5,000 mg/kg to determine tolerance (typical human cancer supplemental amount is only 20 mg/kg). 5,000 mg/kg was administered to 10 mice of both sexes for 14 days. Upon necropsy all organs were CLEAN and there were no clinical signs following oral administration, with darkened urine observed following i.v. treatment. (PHARMAKON USA)

Calvert Laboratories, Inc. performed the chronic toxicity studies (90 days) orally in rats (15 per group in both sexes) at two dosages 18 mg/kg and 36 mg/kg. Chronic studies revealed no animal deaths or clinical symptoms.

Effectiveness

Poly MVA effectiveness was first independently demonstrated on the growth of a glioblastoma tumor cell line in nude mice. Tumors were allowed to establish and mice were divided into 8 groups of 10 mice treated either I.V. or orally daily for 4 weeks with either vehicle or 0.5, 1, or 2 mg/ mouse. After measuring the tumor size twice a week, both routes of administration reduced its size. (Calvert Laboratories, Inc.)

Effectiveness (continued)

Thus far the LAPd complexes have demonstrated anecdotal effectiveness in over 20 different types of cancer (Human dose = 40ml/day). Furthermore, their ability to both quench radical species and shunt electrons down the electron transport chain also make them effective in limiting ischemic damage (Antonawich, et al., Experimental Neu- rology, 2004; Antonawich and Welicky, in preparation, 2004). We have demonstrated that Poly MVA not only protects the CA1 region of the hippocampus from transient global ischemia, even after delayed administration, but maintains behavioral function as well (Human dose = 20ml/day ).

Mechanism of Action

Thus far our studies have demonstrated that the LAPd based compounds, such as Poly MVA, appear to regulate cell death via modulation of apoptosis. How can Poly MVA kill a cancer cell but rescue or provide energy to an ischemic or normal cell? While it has the ability to shuttle energy to each cell, the selective vulner- ability of the cancer cell is due to its disrupted metabolic state. The next few diagrams will outline this mechanism based on the finding in our published data.

When Poly MVA is administered to a cell, electrochemistry data demon- strates the transfer of electrons from the plasma membrane to DNA (since the plasma membrane is a “fluid” and “plastic” structure its integrity is not compromised). However, this transfer is not direct and occurs via the mito- chondria since free lipoic acid will decrease the effectiveness of the LAPd complexes.

Excess energy that travels down the electron transport chain can not be accepted since malignant cells function in an oxygen poor environment (hypoxia). This results in the generation of local radicals at the mitochondrial membrane, facilitation of cytochrome c release and subsequent activation of an apoptotic complex.

The activated initiator caspase will turn on others in the caspase family of enzymes. The effector caspases result in cell destruction and eventually cancer cell death.

It should be noted that nicotine attenuates the ability of the LAPd complex to sequester electrons.

In a healthy or ischemic cell (which was healthy seconds earlier), oxygen is available to quench the excess energy. This will prevent the formation of the apoptotic complex. Furthermore, the mitochondrial permeability transition will be maintained in the ischemic cell. Since Poly MVA is a potent free radical scavenger, any generation of radicals via reperfusion can be quenched.

Therefore, By Providing Poly-MVA as an Alternative Energy Source One Can:

Stabilize the mitochondria in an ischemic cell, as well as quench reperfusion radicals.
Gag a cancer cell on excess energy to facilitate apoptosis

Dr. Frank Antonawich is a Research Scientist in the Department of Neurology at SUNY at Stony Brook, and Professor and Chairperson of Biology at St. Joseph’s College, New York.