Year-End Report 2017
Mitochondrial myopathies are a group of neuromuscular diseases caused by damage to the mitochondria. Some of the more common mitochondrial myopathies include Kearns-Sayre syndrome, myoclonus epilepsy with ragged-red fibers, and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes. The symptoms of mitochondrial myopathies include muscle weakness, exercise intolerance and fatigue, and are often accompanied by other symptoms of genetic mitochondrial disorders such as heart failure or rhythm disturbances, dementia, movement disorders, stroke-like episodes, deafness, blindness, droopy eyelids, limited mobility of the eyes, vomiting, and seizures. The prognosis for these disorders ranges in severity from progressive weakness to death.1) There is a high unmet medical need of new and effective treatment options for mitochondrial myopathy.
A collaboration agreement has been signed with Karolinska Institutet, Stockholm, Sweden, regarding development of NeuroVive’s compound NV556 for the treatment of mitochondrial myopathy (project NVP025). Under the collaboration agreement, the team at Karolinska Institutet will study NeuroVive’s cyclophilin inhibitor compound NV556 and its effects in experimental models of mitochondrial myopathy.
The Karolinska Institutet research team previously published results2) where they show that another cyclophilin inhibitor, ciclosporin, shows mitochondrial protective effects mediated through inhibition of cyclophilin D, resulting in prevention of muscle fiber weakness in an experimental model of mitochondrial myopathy. They have also shown that patients with mitochondrial myopathy have increased levels of cyclophilin D, the target for NeuroVive’s compound NV556. NV556 is expected to have higher specificity and tolerability than ciclosporin, which may facilitate better optimization of dosage.
This collaboration expands NeuroVive’s presence in the genetic mitochondrial disease field, which is a NeuroVive key focus area and where NeuroVive also develops its NVP015 compounds in mitochondrial respiratory chain diseases. The NV556 compound that is studied under this collaboration is targeting cyclophilin D, and has therefore a different and complementary mode of action than the NVP015 compounds which target the respiratory chain supporting cell energy production.
2) Cyclophilin D, a target for counteracting skeletal muscle dysfunction in mitochondrial myopathy. Westerblad H. et al. Human Molecular Genetics, 2015, Vol.24, No 23; 6580-6587.