Pipeline & Indications
MitoChem’s development pipeline is focused on therapeutics that correct mitochondrial dysfunction across neurodegenerative indications.
Amyotrophic Lateral Sclerosis (ALS)
ALS is a fatal neurodegenerative disease. It attacks motor neurons in the brain and spinal cord, causing paralysis, difficulty swallowing and breathing, and ultimately death. Mitochondrial dysfunction is a hallmark feature of ALS.
Fused in Sarcoma (FUS) is a known cause of ALS. In familial ALS, point mutations in FUS’s genetic nuclear localization signal (NLS) interfere with FUS’s ability to enter the nucleus, resulting in a loss of function in the nucleus and toxic aggregation in the cytoplasm where it disrupts cellular metabolism. The severity of the point mutations correlates with the level of cytoplasmic FUS and patient survival. The greater the severity, the shorter the life expectancy.*
Preclinical studies demonstrate MC16 prevents and reverses wildtype FUS mislocalization in epithelial cells.
Retinitis Pigmentosa is a group of rare, heterogenous inherited degenerative eye diseases that lead to vision loss and blindness. RP is caused by genetic mutations that lead to the progressive degeneration of the retina's light-sensitive cells (photoreceptors). There are over 100 genes involved in RP making it particularly challenging to treat. For example there is only one approved gene therapy for a related eye disease, Leber congenital amaurosis (LCA), that treats a small fraction of LCA patients. There remains a large unmet need for therapies that can treat patients regardless of their specific mutation.
Preclinical studies demonstrate MC16 prevents and reverses mutant FUS mislocalization.
Widespread FUS mislocalization
Studies show this mislocalization is widespread in ALS. In both familial and sporadic ALS spinal motor neurons, wild-type FUS accumulates in the cytoplasm creating mitochondrial disruption and axonal transport defects, linking FUS pathology directly to energy failure. ALS and related disorders are classified as nucleocytoplasmic transport diseases — where restoring protein localization can rescue energy metabolism.**
Retinitis Pigments (RP)
The visual systems ranks among the highest in the body for energy consumption. Photoreceptors convert light to neurochemical signals, a task that entails unusually high energy requirements, calcium ion transients, and oxidative stress. The visual system is particularly vulnerable to functional deficits induced by deficiencies in energy metabolism**.
FUS alterations and proteotoxicity is a proposed disease mechanism in retinitis pigmentosa (RP), with FUS aggregation in multiple retinal cell layers. *
MitoChem’s approach
MC16 prevents and reverses FUS mislocalization in ARPE-19 retinal cells. By targeting the metabolic crisis that underlies an early root cause of degeneration, we have developed a gene mutation agnostic therapeutic with potential to treat all genetic variants of RP.
Preclinical studies in animals demonstrate MC16 protects structure and improves function of photoceptors in RP phenotypes found in humans.