recessive dystrophic epidermolysis bullosa
Epidermolysis bullosa is a disease affecting the function of type 7 collagen at the interface between the dermis and the epidermis.
APTEEUS wishes to engage its first drug candidate in the development of a topical skin product to treat this pathology. TEE786 is a molecule whose demonstrated pharmacological activities will have a beneficial effect on wound healing in patients with bullous epidermolysis. Success in this first development may open up several extensions of indications in other dermatoses.
Fumarase is an enzyme mainly involved in the krebs cycle, essential for the production of energy by the mitochondria. Its deficiency leads to fumaric aciduria (ORPHA:24), a disease that disrupts the normal development of the child. It is an ultra-rare disease with about 100 cases reported to date.
Apteeus currently uses a child’s cells to highlight the defect of fumarase in vitro.
mecp2 duplication Syndrome
MeCP2 gene duplication syndrome is a neurodevelopmental disease whose symptoms are caused by overexpression of the MeCP2 protein (ORPHA:85281). The prevalence of MECP2 duplication syndrome is unknown; more than 200 affected individuals have been described in the scientific literature. It is estimated that this condition is responsible for 1 to 2 percent of all cases of intellectual disability caused by changes in the X chromosome.
APTEEUS has developed a semi-quantitative measurement of the MeCP2 nuclear protein by immunocytochemistry. The screening of TEE Library identified several MeCP2 modulators capable of restoring normal protein expression using the cells of three patients with the syndrome. These molecules will be evaluated on neurons and on an animal model of the disease in collaboration with other research teams.
MeCP2 is also the protein responsible for Rett Syndrome when it is not functional. It is also pointed as a key regulator in other neurological disorders and cancer.
Acid ceramidase deficiency
Ceramidease (acid) is a lysosomal enzyme involved in the recycling and catabolism of ceramides. Its deficiency leads to an accumulation of ceramides in the lysosome and other organelles and disrupts cell metabolism (ORPHA:333 and 2590). Proximal spinal muscular atrophy syndrome-progressive myoclonic epilepsia or SMA-PME is a manifestation of ceramidease deficiency affecting only about ten patients. It is an ultra-rare disease. Farber’s disease, which has more severe and early symptoms, affects a few more patients.
Apteeus is currently developing the screening methodology on the cells of a child with SMA-PME.
The ACOX1 protein, for Acyl-CoEnzymeA oxidase type 1, is a peroxisomal protein involved in the beta-oxidation of very long chain fatty acids in the peroxisome (ORPHA:2971). Peroxisomal acyl-CoA oxidase deficiency is an ultra-rare disorder. Its prevalence is unknown. Only a few dozen cases have been described in the medical literature.
It is our technology based on liquid chromatography coupled with mass spectrometry that has enabled us to identify TEE886, a drug candidate that restores a normal level of very long fatty acids in the cells of an ACOX1 deficient child. The child is currently monitored to evaluate the progress of his pathology under treatment.
d-bifonctionnal protein deficiency
Bi-functional protein D is a peroxisomal enzyme involved in the beta-oxidation of very long fatty acids. Its deficiency leads to an accumulation of very long fatty acids and disrupts the other functions of the cell (ORPHA:300). D-bifunctional protein deficiency is estimated to affect 1 in 100,000 newborns. The prevalence is very low, it is an ultra-rare disorder.
Apteeus used liquid chromatography coupled with mass spectrometry to highlight the accumulation of very long chain fatty acids in Noé’s cells in culture. Miniaturized and automated, the test has made it possible to identify several drugs. Unfortunately time and disease have been against us. We were unable to assess the benefit-risk balance of its use on Noé.