Why Mitochondria Therapy?
When Mitochondria, a form of bacteria at the time, merged with what was a simple cell-organism, the ensuing symbiosis gave rise to complex life. Today, mitochondria are present in almost every human cell. They turn oxygen into energy, play a central role in intracellular communication and are involved in the processes of cell proliferation as well as death. When they are damaged, due to disease or genetic defects, cell functions deteriorate.
Whilst known as disease targets for some time, mitochondria have proven difficult to treat. But what if it was possible to replace and augment damaged mitochondria? Therapeutic Mitochondria Transplantation holds the potential of sustainably affecting mitochondria function, reinvigorating or amplifying the cellular energy metabolism.
Beyond amplifying the cell’s energy metabolism, mitochondria can also serve as a non-viral vehicle for the delivery of therapeutic payloads with three distinct advantages over conventional carriers:
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Distinct biodistribution, enabling minimal or non-invasive delivery to solid organs beyond the liver
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Superior safety profile, supporting high and repeated dosing without immune activation
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Superior carrying capacity, allowing very large and multiple payloads in a single delivery
These properties have earned mitochondria-based therapy growing scientific traction, with more than 500 publications on the therapeutic potential of mitochondria, and results reproduced across disease models, laboratories, and countries. Decades of academic research are now converging to establish mitochondria as a novel therapeutic modality.
MITOCHONDRIA ARE INTIMATELY TIED TO THE ORIGIN OF COMPLEX LIFE
Mitochondria are membrane-bound cell organelles that generate most of the energy needed to power the cell's biochemical reactions. In a process referred to as symbiogenesis, mitochondria are said to have merged with a simple cellular organism, giving rise to complex life and its evolution. In this process, Mitochondria took over vital roles within the cell, including:
Our approach
Employing proprietary preparation and delivery techniques, cellvie is transplanting mitochondria directly into compromised cells. The organelles penetrate the cell walls through endocytosis and merge with the mitochondrial network, to contribute to the cells' energy metabolism.
GENETIC DISEASES
Leveraging their efficient cellular uptake and endosomal release capacities, cellvie is employing modified mitochondria as a novel vector to target genetic diseases. Indications addressable by mitochondria-enabled gene delivery span disorders across the skin, kidney, brain, and lung. cellvie is pursuing Epidermolysis bullosa as its first indication, with plans to expand from there.
First Application: Epidermolysis bullosa
Epidermolysis bullosa (EB) is a rare and devastating genetic disease. Patients – many of them children – suffer from fragile skin, chronic wounds, pain, infections, and complications affecting internal tissues. We focus on the most severe form, Dystrophic EB (DEB), in which a deficiency in the COL7A1 gene leaves patients without functional Type VII Collagen, the protein that anchors the skin’s layers together. The slightest touch results in blisters and open wounds. (More information at DEBRA.)
Despite recent therapeutic advances, significant unmet need remains, particularly around the speed and quality of wound healing, the breadth of wounds that can be treated, and the safety profile of existing modalities.
Using modified mitochondria, cellvie is developing a topical mitochondria therapy that delivers a functional copy of COL7A1 to affected skin, restoring Type VII Collagen expression and addressing the root cause of the disease. Beyond the delivery of the COL7A1 payload, mitochondria themselves are anticipated to contribute to wound healing by attenuating inflammation and fibrotic signaling, offering a unique therapeutic effect that complements the plasmid payload.
Once clinically proven, the objective is to advance a pipeline of EB-focused treatments. Potential expansions include prophylactic treatment, treatment of mucosal regions, and delivery of multiple payloads per mitochondrion to further improve wound healing and reduce the incidence of cutaneous squamous cell carcinoma.
Success in Epidermolysis bullosa would translate well to other indications where mitochondria-enabled delivery offers a distinct advantage.
Ischemia Reperfusion Injury
In the first application for unmodified mitochondria, we seek to treat ischemia-reperfusion injury, with kidney transplantation as the first indication.
Ischemia-reperfusion injury is the world’s number one killer. It is ubiquitous - arising whenever blood flow is interrupted and subsequently reintroduced. The damage unfolds in two waves. The first comes with ischemia itself: deprived of oxygen, cells deteriorate and mitochondrial function is impaired. The second comes with reperfusion: although it is the only means to rescue affected tissue, the sudden return of oxygen overwhelms the damaged mitochondria, which can no longer convert oxygen into energy. Free radicals form and cell death ensues.
Medical conditions giving rise to Ischemia-reperfusion injury include heart attacks, stroke, long surgical procedures, and organ transplantation. cellvie is pursuing kidney transplantation as its first indication, with plans to expand from there.
First application: Kidney transplantation
With 100,000 patients on the waiting list for a kidney and 12 of them dying each day, the need to improve access to and performance of these grafts is dire. Ischemia-reperfusion injury (IRI) is a key constraint on donor organ availability and a key driver of post-transplant performance, and longevity: the fear of ischemic damage limits allowable transport times and donor selection, and IRI is closely linked to delayed graft function (DGF), commonly defined as the need for dialysis within the first week of transplantation. DGF in turn drives reduced long-term kidney survival and higher direct treatment costs.
Success in kidney transplantation would translate well to other IRI indications, including other solid organ transplantations, long-clamp-time cardiac surgery, and heart attacks.
PIPELINE
We seek to bring about Therapeutic Mitochondria Transplantation as a new treatment modality, building a pipeline of applications beyond ischemia reperfusion injury.
We are particularly interested in the potential of slowing or reversing degenerative processes caused as humans age, that are directly connected to mitochondria function.
