Announcing Success in the MitoSENS Project Crowdfunded at Lifespan.io in 2015
I'm very pleased to report that that the SENS Research Foundation project on mitochondrial allotopic expression (MitoSENS) that was crowdfunded at Lifespan.io this time last year has achieved success. The two target mitochondrial genes have been moved to the cell nucleus, and suitably altered so that the proteins produced return to the mitochondria. This means that cells so treated are immune to age-related damage to those two genes in the mitochondrial genome: they will still construct and make normal use of the proteins encoded in those genes as though nothing happened. Given that mitochondrial DNA damage is an important contribution to the aging process, progress on this front is very welcome.
The crowdfunded work was the final sprint at the end of a years-long project conducted with minimal funding, and it is great to see success. Congratulations are due to the researchers involved. There are thirteen mitochondrial proteins in total that are thought to be all that is needed to move into the nucleus. Allotopic expression of one other mitochondrial gene is solidly complete, and is the basis for the therapies under development at Gensight. Another two genes are somewhere in the middle of the process in the SENS Research Foundation network of researchers. This leaves a further eight genes to go. As ever, this is work that is in search of much greater funding: the researchers are always ready to go, and the more that we can do to help deliver that funding, the sooner we'll see rejuvenation therapies in the clinic.
Note that you may need to click the updates tab on the fundraiser page in order for the updates to load:
Hi everyone, it's been an amazing few months. In short, we have been tremendously successful in our efforts to rescue a mutation in the mitochondrial genome! Essentially we've shown that we can relocate both ATP6 and ATP8 to the nucleus and target the proteins to the mitochondria. We can show that the proteins incorporate into the correct protein complex (the ATPase) and that they improve function resulting in more ATP production. Finally, we show that the rescued cells can survive and grow under conditions which require mitochondrial energy production while the mutant cells all die.
We have finished writing up our results and submitted them for review and publication. It may take a while for our results to be published (the peer review process can be lengthy) but as soon as it is I'll post an update here so you can see the full paper. We have also started the project that you helped us get to our stretch goal on. We have made all the combinations of mitochondrial targeting sequences with ATP6 that we proposed and are now working on testing them. I'll let you know when we know more. Thank you so much for your support!
How about an individual 60k fundraiser for each of the remaining 8 genes?
Actually as Gensight have already initiated an ND1 research program, and will probably take on ND6 too, that would be a 60k fundraiser times 6 remaining genes.
"LHON originates from mutations in three NADH Dehydrogenase mitochondrial genes: ND1, ND4 and ND6. Because ND4 mutations account for more than 75% of the LHON population in North America and Europe, we chose to first focus on this specific mutation. We have demonstrated the feasibility of using the MTS technology platform for the treatment of LHON due to the ND4 gene mutation in animal studies. We plan to use our MTS technology platform to address other LHON mutations and have already initiated a research program for our next potential product candidate, GS011, which targets the ND1 gene mutation.
We believe that our MTS technology platform can also be used to address diseases outside of ophthalmology that involve defects of the mitochondrion, such as neurodegenerative disorders. "
Unfortunately it isn't as simple as a $60,000 fundraiser per gene. As I noted, the ATP6 and ATP8 fundraiser project was the final portion of a much longer research effort. Further, a couple of the remaining genes will be more expensive because there is a lot of work remaining to figure out the transport back to the mitochondria.
It still isn't an enormous amount of money in the grand scheme of things. Probably millions, but not many millions.
In that case I hope allotopic expression doesn't wind up like DRACO, always a few million short of getting anywhere...
Speaking of Lifespan, the current senolytics project just got $10k from a Russian marketing VP and a Brazilian singulatarian.