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The QE3 Study: Finding Ways to Slow the Progression of PD

Mar 29 2010

By Flint Beal, M.D.

Although tremendous advances have been made in the treatment of Parkinson’s Disease (PD), they have mostly been focused on symptomatic improvement.  Currently, available treatments address tremor, rigidity and slowness of movement experienced by people living with Parkinson’s. However, they do not have any effect on slowing the progression of the illness and treating the underlying disease process.  This is a major area of therapies development for people living with Parkinson’s.  If one could slow the disease progression, one could avoid many of the long range complications of PD such as dyskinesias and eventually perhaps cognitive impairment.

While the cause of PD still remains to be clarified, substantial clues have been obtained over the last few decades.  One of these clues is the scientific rationale behind “The Effects of Coenzyme Q10” study (called the “QE3”study).  Coenzyme Q10 (CoQ10) is a compound which is naturally found within the body, and present in all cells, where it plays a critical role in generating adenosine triphosphate (ATP) within mitochondria.  In addition, CoQ10 has been shown to be a very potent scavenger of free radicals.  CoQ10, therefore, has two potential beneficial actions.  It improves energy production by mitochondria, and blocks oxidative damage produced by free radicals.  As such it is a very promising agent for the treatment of the underlying disease process of PD.  Please see below for more details about the potential relationship between mitochondria function and Parkinson’s disease.

CoQ10 has been demonstrated to be effective in animal models of PD produced by the toxin MPTP, which is known to cause a parkinsonian syndrome in humans.  It also has been shown to block damage produced by other toxins such as rotenone, which produces a model of PD in several different species.  Initial clinical trials done in people with PD show therapeutic benefits in slowing the progression of the disease as assessed using a grading scale, the Unified Parkinson Disease Rating Scale (UPDRS).  CoQ10 is unique in that it is well-tolerated with very minimal if any side effects.

These properties, the safety of CoQ10, as well as its efficacy in preventing neuronal damage caused by toxins which produce PD, provide a strong rationale for the current QE3 phase III clinical trial. If this trial is successful it will lead to further studies of agents that can act through similar mechanisms.  It is possible that improved agents may be able to be completely halt the disease process.  At the very least, the outcome of the trial will provide a strong piece of evidence, that mitochondrial dysfunction and oxidative damage, play an important role in the disease process of PD.   We believe that the outcome of this clinical trial is, therefore, of great import, since it will shape the future of PD treatments. For more information please see the QE3 PDtrials posting.

Why is Mitochondria Function Important to Parkinson’s Disease Research?

There is increasing evidence that mitochondrial dysfunction and oxidative damage may play a key role in the development of PD.  Mitochondria are part of the machinery found within the cell that are referred to as the “powerplant” of the cells since they produce all of the energy which is then exported into the rest of the cell in the form of ATP and phosphocreatine, which then provide the energy for all of the other processes within the cell.

When the function of mitochondria becomes impaired, as may happen in PD, energy production decreases and cells become stressed, starved for energy, and vulnerable to cell death. Another consequence of mitochondrial dysfunction is that toxic by-products of energy production are not always handled properly by the cell.  These toxic by-products are oxygen-based chemical compounds called free radicals. When uncontrolled, free radicals can progressively damage the machinery inside of a cell and eventually kill the cell in a process called oxidative damage.

While the role of mitochondria and oxidative damage in PD has not been proven, there is strong evidence supporting this from recent genetic discoveries in certain forms of inherited PD.  Each of these forms of PD is the result of a defect in a different protein, yet all of the proteins interact with the cell’s mitochondria.  It has been shown that one of the proteins involved, DJ1, plays a critical role in defenses against oxidative damage while two of the other proteins, PINK1 and parkin, are involved in the removal of damaged mitochondria from the cell. As a consequence of these findings, a great deal of interest has been focused on agents that can improve mitochondrial function and block oxidative damage.

Dr. Flint Beal is the Anne Parish Titzell Professor of Neurology and Neuroscience at Weill Medical College of Cornell University.