Mitochondria are the power plants of the cell, producing chemical energy store molecules to power cellular processes. They are also embedded deeply into may core functions of the cell, from replication to programmed cell death. Mitochondrial function declines throughout the body with age, for reasons that are likely downstream of other more fundamental damage. Mitochondrial dynamics change in ways that make mitochondria more resilient to removal via mitophagy when worn or broken, and mitophagy itself loses efficiency. This may or may not be connected to mitochondrial DNA damage. It is unclear as to whether the progressive accumulation of mutations in mitochondrial DNA has a broad effect on function in most cells, or only results in a small number of highly dysfunctional cells.
Regardless, is it possible to effectively address mitochondrial dysfunction by delivering new mitochondria in large volumes into the body? It is clearly the case that cells ingest whole mitochondria and put them to work when given the opportunity. This option hasn't been aggressively pursued to date by the core rejuvenation biotechnology community, as it seems likely that it could only have a short term benefit. One can argue that functional mitochondrial placed into a dysfunctional environment will soon go the way of their predecessors, and for the same reasons: altered dynamics and diminished mitophagy. Similarly cells overtaken by dramatically broken mitochondria are overtaken because those mitochondria have a replication advantage over their functional peers. In both cases we suspect that transplanted mitochondria wouldn't last in their pristine state.
Now, however, a number of groups are working on practical approaches to mitochondrial transplantation, including today's example, focused initially on applications in medicine in which short term benefits are sufficient. It will be interesting to see how these efforts progress. If it is possible to restore mitochondrial function broadly in the body for at least months, that may prove to be worth the effort in the context of aging. There are other interesting questions to answer along the way, as well. For example, what happens when you replace a large fraction of native mitochondria with mitochondria that contain a different mitochondrial DNA haplogroup? Possibly nothing bad. Perhaps one can swap out any mammal's mitochondrial genome for a better, more efficient, more resilient, artificially augmented mitochondrial genome without any downside - a worthy long-term goal if it is straightforwardly attained. But we just don't know in certainty.
Cellvie was founded in the US in 2018 and is headquartered close to Zürich, Switzerland. The founders pioneered the approach of mitochondria augmentation and replacement and the team has now set out to leverage the therapeutic potential of mitochondria for a new treatment modality in ischemia-reperfusion injury, aging and beyond. Mitochondria play a crucial role in the aging process, activating factors and metabolic pathways involved in longevity. Their dysfunction impacts on both lifespan and healthspan. "But treating mitochondria has proven to be an arduous challenge. That is why we turned to introducing healthy, viable mitochondria into cells where these organelles are impaired. To great effect. We can sustainably reinvigorate cells' failing energy metabolism."
The potential of therapeutic mitochondrial transfer was recently demonstrated in a clinical investigation at Boston Children's Hospital; paediatric patients on heart-lung-support after suffering a cardiogenic shock received the treatment to revitalise their heart muscle. 80% of these children experienced myocardial recovery, which compares with an expected 29%. "The investment will enable us to pursue the platform broadly, including a first application in aging, where the need for mitochondria-recovery is particularly dear."
To date, Cellvie has focused primarily on ischemia-reperfusion injury (IRI), which manifests itself whenever the blood flow to a part of the body is interrupted and subsequently reintroduced. Well-known medical conditions causing IRI include heart attacks, strokes, and organ transplantation. Cellvie is also pursuing an indication in organ transplantation, for which the FDA awarded orphan drug designation in 2020. The capital injection will be employed for preparing for market, expanding Cellvie's product pipeline and to prepare an IND submission for a clinical study in kidney transplantation.