Mitochondrial Gene Replacement, Now in Primates

Mitochondria are the cell's power plants, important in the operation of metabolism, how that metabolism determines life span, and many age-related diseases. As described in the mitochondrial free radical theory of aging, a small number of mitochondrial genes are known to be crucial to its operation as the cell's power plant. Damage to those genes is a natural consequence of the operation of a mitochondrion, and leads to a Rube Goldberg sequence of events in which is a healthy cell is turned into a damaged cell that spews forth damaging biochemicals into your body. As those errant cells accumulate, their actions collectively give rise to many of the unwelcome forms of change and damage that come with age: systems failing, organs shutting down, and important biochemical processes running awry because their component molecules are corrupted.

Given all this, we can see that the ability to replace genes in mitochondrial DNA is a foundation for methods of repairing and eliminating this contribution to the aging process. The course of human life suggests that such a working technology would only have to be applied once every few decades.

Of all the branches of potential longevity science, replacement of mitochondrial DNA is one of the most advanced (beyond stem cell research and regenerative medicine of course, which benefits from a far larger research community and funding base). Replacement of all mitochondrial DNA was demonstrated in mice through protofection in 2005, and moving mitochondrial genes into the cell nucleus as an alternative to direct replacement was demonstrated in mice in 2008. That second option is not as simple as you might think in an age of genetic science: copying the gene into the nucleus is a straightforward use of established technology, but that done you still have to manipulate the cell into transporting the proteins produced by that gene back into the mitochondria without breakage. Fortunately, this breakthrough was made, so full steam ahead there.

But back to the straight replacement of entire damaged mitochondrial genomes. Here is a recent report of this goal achieved in primates, though this is a pre-embryonic manipulation performed on a single cell rather than a global change in all the cells of an adult. The point of interest is that it worked and the resulting offspring seem fine; it provides further evidence for the safety of replacing all of a human's mitochondrial DNA (mtDNA):

Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring.

The underlying technologies are within a few years of completion by the look of it. At that point the real issue becomes one of regulation; the FDA does not permit treatments for aging or changes that happen with aging that have not been lobbied into a designation as an official disease. So any significant progress towards therapies aimed at repairing mitochondrial damage of aging will have to be made outside the regulatory systems of the largest markets. With this science - and many other fields of medicine - so very far ahead of what regulators permit, the breaking point at which large for-profit development groups abandon the system to operate in more permissive regions has to arrive at some near future date.

ResearchBlogging.orgTachibana, M., Sparman, M., Sritanaudomchai, H., Ma, H., Clepper, L., Woodward, J., Li, Y., Ramsey, C., Kolotushkina, O., & Mitalipov, S. (2009). Mitochondrial gene replacement in primate offspring and embryonic stem cells Nature DOI: 10.1038/nature08368

Comments

Nice article or paper.,The Mitochondrail DNA Replacement therapy might provide exlusive contribution for health care especially for the sack of VIP's. Before human trials could be started the procedure should be followed for distinct species ie panda .If late term harms found in these species as in the case of Dolly , it could be optimized before criticist gain control. CONGRATULATION

Posted by: Muhammad Nawaz Ali at August 27th, 2009 10:28 AM

Perhaps a political action committee could be established to get the FDA to recognize aging as a treatable disease.

Posted by: kurt9 at August 27th, 2009 10:43 AM

Complete disengagement seems a better use of resources.

If you look at the way lobbying works presently, many millions of dollars and years are spent on things like the present efforts to get the FDA to recognize sarcopenia (age-related muscle loss) as an official disease. This is the present scale of thinking - that it takes that much time and money just to carve off one tiny little approval to proceed.

No-one involved in the institutions of lobbying and regulation has any short-term incentive to take a short cut when doing things the present way is how they make their living.

Posted by: Reason at August 27th, 2009 12:32 PM

The FDA will finally warm up to it when they see a determined community successfully putting it into practice. Innovation often occurs on the fringe and is later accepted by the "establishment" rather than the other way around.

Posted by: shegeek at August 28th, 2009 8:11 AM

Once the technology exists, people will gladly travel many miles for an opportunity to extend their lives and health. Also, countries willing to sponsor and embrace such innovation, like all innovation, will gain a technological and consequently economic advantage. In other words, once it has been proven to work, it does not matter what stance the FDA takes, they will soon find themselves irrelevant.

Posted by: Ren at February 5th, 2010 12:53 AM

I believe I am suffering from mitochondrial damage from taking large doses of statin drugs. The damage or mutation is said to occur by a drop in available coenzyme Q10, which is not only necessary for ADP phosphorylation, but also for guarding against damage to mitochondria by Reactive Oxygen Species (ROS) which floods the region. My symptoms include muscle stiffness, neuropathy, weakness and exhaustion. No neurologist or rheumatologist has helped as I suspect they deny this effect of statin drugs. I stopped taking the drugs 5 years ago. If you need to cite a condition to help your work get official recognition, this is a possibility, and probably suffered by large numbers of people around trhe world
Fred Potter

Posted by: Fre Potterd at August 1st, 2012 1:07 PM

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