Common Pathogenic Mechanisms and Our Medical Hypothesis

The essence of our medical hypothesis is the strong correlation – and we believe, causality – between dysregulated fatty acid oxidation and the development of neurological disorders. Strongly up-regulated fatty acid oxidation is an important, shared pathogenic mechanism that underlies processes such as autoimmune responses, mitochondrial dysfunction, dysregulated glucose metabolism and ROS production.

Pre-clinical data from animal models of ALS, Parkinson’s, MS and Depression show that down-regulating fatty acid oxidation has a profoundly positive effect on survival and quality of life.

Observation

Neurologic diseases with different etiology and seemingly unrelated symptoms share common pathogenic mechanisms:

  • Inflammatory component
  • Stress
  • Upregulated fatty acid oxidation
  • High prevalence of depression

Hypothesis

Altered fatty acid oxidation is an important, shared pathogenic mechanism that underlies processes such as autoimmune responses, mitochondrial dysfunction, dysregulated glucose metabolism and ROS production

Data

Down-regulating fatty acid oxidation has profound impact on survival and quality of life in animal models in ALS, Parkinson’s, MS and Depression

In ALS patients fatty acid oxidation is upregulated, glucose metabolism is downregulated

Glucose metabolism measured in the brain of  in 4 ALS patients using FDG PET scan.

Reduced glucose metabolism is shown in the green areas of the left 3 scans and blue areas of right 3 scans.

The up-regulated lipid metabolism observed in animal models of neurological disorders are also found in human ALS patients. Sustained up-regulated lipid metabolism causes lipid deficit and inflammation resulting in mitochondrial dysfunction and neuronal stress. We believe this is a key pathogenic mechanism in the development of ALS and some other neurological disorders and it is the target of our drug candidate.

From Preclinical to Clinical Development

Our mission now is to proceed from preclinical studies to human trials. We are working to select and optimise the best variant of our drug candidate and plan to complete toxicology studies and GMP production in 2020 and to commence first-in-human studies in 2021.