Contributions
Abstract: P1654
Type: LB Poster
Abstract Category: Late Breaking News
Background: Multiple Sclerosis has until now been regarded as a chronic, inflammatory and autoimmune disease, which is characterized by damage to myelin sheaths of neurons. However, a new hypothesis of the pathogenesis of Multiple Sclerosis concerns an unbalance in metabolic pathways and more particularly an upregulated lipid metabolism and consequently inflammation. Lipids are crucial for the central nervous system as they constitute myelin sheaths and shield myelin basic protein for the immune system. In Multiple Sclerosis, disturbances in metabolic pathways occur, which results in upregulated lipid metabolism and thereby, changes in composition and concentrations of lipids in the brain. In order to reverse the lipid metabolism back to glucose metabolism a key molecule involved in lipid metabolism, called Carnitine Palmitoyl Transferase-1 (CPT-1), can be blocked. This block of CPT-1 results in lipidation of myelin sheath proteins, reparation of myelin sheaths, shielding of myelin sheath proteins for the immune system and restoration of signaling capacity.
Methods: Mice and rat experimental autoimmune encephalomyelitis (EAE) models of Multiple Sclerosis were established in order to test efficacy of Etomoxir, a CPT-1 antagonist.
Results: The mice EAE model shows > 50 % healthy mice after two weeks of treatment with Etomoxir started at day 10. Treatment with Etomoxir, started at day 7, results in 25 % disease free rats. Moreover, Etomoxir treatment is compared to Interferon-β treatment, the current standard treatment of Multiple Sclerosis, in a rat EAE model. Etomoxir treatment, started at day 1 and day 5, shows highly significant superior efficacy compared to Interferon-β treatment at day 1 and day 5.
People carrying CPT-1A mutations are protected from developing Multiple Sclerosis and other CNS diseases. These mutations reduce or delete the activity of CPT-1A. Populations such as Hutterites and Inuits are carrying CPT-1A mutations and have a prevalence of Multiple Scleroses of 1/1100 and 1/50000, respectively. Normally, the prevalence in these regions is 1/350.
Phase two clinical trial using Etomoxir for treatment of Acute Optic Neuritis and Secondary Progressive Multiple Sclerosis is being organized to start in 2017 by Meta-IQ ApS.
Conclusions: CPT-1 is a key molecule involved in lipid metabolism and blocking the molecule by Etomoxir opens up for a new treatment strategy for Multiple Sclerosis.
Disclosure: Anne Skøttrup Mørkholt, Agnete Larsen, Shohreh Issazadeh and Søren Nielsen: nothing to disclose.
Jette G. K. Nieland: has ownership in Meta-IQ.
John Dirk Nieland: consultant for Meta-IQ.
Abstract: P1654
Type: LB Poster
Abstract Category: Late Breaking News
Background: Multiple Sclerosis has until now been regarded as a chronic, inflammatory and autoimmune disease, which is characterized by damage to myelin sheaths of neurons. However, a new hypothesis of the pathogenesis of Multiple Sclerosis concerns an unbalance in metabolic pathways and more particularly an upregulated lipid metabolism and consequently inflammation. Lipids are crucial for the central nervous system as they constitute myelin sheaths and shield myelin basic protein for the immune system. In Multiple Sclerosis, disturbances in metabolic pathways occur, which results in upregulated lipid metabolism and thereby, changes in composition and concentrations of lipids in the brain. In order to reverse the lipid metabolism back to glucose metabolism a key molecule involved in lipid metabolism, called Carnitine Palmitoyl Transferase-1 (CPT-1), can be blocked. This block of CPT-1 results in lipidation of myelin sheath proteins, reparation of myelin sheaths, shielding of myelin sheath proteins for the immune system and restoration of signaling capacity.
Methods: Mice and rat experimental autoimmune encephalomyelitis (EAE) models of Multiple Sclerosis were established in order to test efficacy of Etomoxir, a CPT-1 antagonist.
Results: The mice EAE model shows > 50 % healthy mice after two weeks of treatment with Etomoxir started at day 10. Treatment with Etomoxir, started at day 7, results in 25 % disease free rats. Moreover, Etomoxir treatment is compared to Interferon-β treatment, the current standard treatment of Multiple Sclerosis, in a rat EAE model. Etomoxir treatment, started at day 1 and day 5, shows highly significant superior efficacy compared to Interferon-β treatment at day 1 and day 5.
People carrying CPT-1A mutations are protected from developing Multiple Sclerosis and other CNS diseases. These mutations reduce or delete the activity of CPT-1A. Populations such as Hutterites and Inuits are carrying CPT-1A mutations and have a prevalence of Multiple Scleroses of 1/1100 and 1/50000, respectively. Normally, the prevalence in these regions is 1/350.
Phase two clinical trial using Etomoxir for treatment of Acute Optic Neuritis and Secondary Progressive Multiple Sclerosis is being organized to start in 2017 by Meta-IQ ApS.
Conclusions: CPT-1 is a key molecule involved in lipid metabolism and blocking the molecule by Etomoxir opens up for a new treatment strategy for Multiple Sclerosis.
Disclosure: Anne Skøttrup Mørkholt, Agnete Larsen, Shohreh Issazadeh and Søren Nielsen: nothing to disclose.
Jette G. K. Nieland: has ownership in Meta-IQ.
John Dirk Nieland: consultant for Meta-IQ.