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Mitochondria transplants at risk of rejection

Tuesday, 1 October, 2013

Those mitochondrial transplants (or ‘three parent IVF’ as it is innaccurately called at times) that I’ve blogged about before (here, here and here) might have a few side effects on gene expression. Replacing mitochondria affected by a genetic disease with those from a gene free donor has been compared to replacing faulty batteries in a camera with fresh new ones. But a recent policy opinion piece published in Science (Reinhardt et al 2013) suggest this analogy might not be totally accurate. One of the authors, Edward Morrow, is quoted in New Scientist:

“For a modern camera you’ve not only got to have the right brand of battery, but the right size, shape and voltage. There are all these parameters you have to have right. You can’t just go into a shop and buy any old one.”

As explained in the piece in Science, the mitochondria of some organisms like fruit flies, mice and monkeys has been shown to interact with the genes being expressed in the nucleus, and thus it probably does the same in humans. Non-invasive methods of replacing mitochondria have been used in most of these studies, which involves mating a male mouse of one line with a female mouse of another line, to produce mice with the mitochondrial DNA of line 2. These offspring were then only crossed to line 1, which after a few generations produces mice that mostly have nuclear DNA of line 1 but the mitochondrial DNA (mtDNA) of line 2 (this is sort of similar to if your mother’s mother’s mother was from a totally different ethnicity to the rest of your family). The results of these experiments were that mice with a ‘mismatch’ had reduced exercise capacity (Nagao et al 1998) and reduced learning ability (Roubertoux et al 2003).

Thus, it’s at least theoretically possible these ‘rejection’ side effects might exist in humans too. We just don’t know, it’s a different species and a different method of mitochondria replacement to those studies. This therapy has been tentatively approved by the Human Fertilisation & Embryology Authority in the UK, and the UK government is drafting regulation for the use of this therapy. This paper shouldn’t change that, as any new treatment is likely to have side effects. The question is whether it’s worth it. I agree with how the Science piece concludes:

Assessing the costs and benefits of MR [mitochondrial replacement] treatment requires that prospective patients are as fully informed as possible. The difference across patients in the severity of expected offspring symptoms in the event that MR treatment is not taken will shape the decision of choosing the treatment versus waiting for the outcomes of further research. Some families who are predicted to be, or who have previously conceived offspring that were, severely afflicted by mtDNA diseases are more likely to be prepared to take the risk. Others whose children are expected to suffer less detrimental symptoms, cognition problems or infertility, may wish to wait for further empirical clarification of the risks involved.

This treatment is very promising for severe mitochondrial diseases. For milder conditions, it might not be worth the risk until we know how the mitochondria and the nucleus interact, and can better work out what mitochondria a good donor needs to have for any given patient.

 

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