Description of the Project

Project description

Mitochondrial dysfunction is a major hallmark of various neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and Amyotrophic Lateral Sclerosis (ALS). The links between mitochondrial dysfunction and the onset and progress of some of these diseases, however, still needs to be explained in more detail. In diseases where this link is already established, the question remains whether drugs developed with regard to specific targets or mechanisms involved in mitochondrial dysfunction can affect the diseases in question.

MitoTarget is an ambitious project aimed at providing solid data to better understand and exploit the circumstantial evidence linking mitochondrial dysfunction with neuronal dysfunction culminating in neurodegenerative diseases.

A translational research program lasting 36 months will bring together a unique partnership between scientists, a seasoned team of clinical investigators and the company Trophos (www.trophos.com) that has identified a novel compound, TRO19622 (olesoxime), that targets mitochondria and has powerful neuroprotective and neuroregenerative activities.

Alongside, and orchestrated by Trophos as the coordinator of the project, MitoTarget will generate a more comprehensive insight into the mechanisms leading to mitochondrial impairments and establish their clinical relevance in the severe orphan neurodegenerative disease - ALS.

If successful, it is expected that from this proof of principle a new class of therapeutic agents targeting the underlying mitochondrial dysfunction in neurons, or their supporting cells, will emerge. Results of the project have the potential to create a new paradigm for the drug discovery and treatment for neurodegenerative diseases.

Project objectives

MitoTarget's objectives are:

1. To gain a more comprehensive insight into the mechanisms leading to mitochondrial dysfunction and thereby the neuronal dysfunctions associated with neurodegenerative diseases.
2. To establish if these mechanisms are amenable to therapeutic intervention in humans, employing a new class of therapeutic agent targeting the underlying mitochondrial dysfunction in neurons or their supporting cells.
   • Provide a new or enlarged insight into how mitochondrial processes are involved in neuronal plasticity - defined by the ability of neurons to adapt their structure and function in response to the physiological and patho-physiological changes in their tissue.
   • Increase our understanding of how mitochondrial processes are involved in the pathogenesis and/or worsening of neurodegenerative disorders.
   • Provide the evidence that these mitochondrial processes are addressable in humans through the completion of a phase II clinical trial in ALS using a new mitochondrial targeted compound, and that such compounds provide a benefit to patients suffering from neurodegenerative diseases.
   • Allow subsequent development of better diagnosis and follow-up of neurodegenerative diseases using newly identified biomarkers of mitochondrial dysfunction.

Should those objectives be reached, MitoTarget would therefore be able to:

1. Provide a new or enlarged insight into how mitochondrial processes are involved in neuronal plasticity - defined by the ability of neurons to adapt their structure and function in response to the physiological and patho-physiological changes in their tissue.
2. Increase our understanding of how mitochondrial processes are involved in the pathogenesis and/or worsening of neurodegenerative disorders.
3. Provide the evidence that these mitochondrial processes are addressable in humans through the completion of a phase II clinical trial in ALS using a new mitochondrial targeted compound, and that such compounds provide a benefit to patients suffering from neurodegenerative diseases.
4. Allow subsequent development of better diagnosis and follow-up of neurodegenerative diseases using newly identified biomarkers of mitochondrial dysfunction.