BioWorld International Correspondent

PARIS - Trophos SA was awarded a Therapeutics Development Initiative grant by the Michael J. Fox Foundation (MJFF) to finance the continued evaluation of compounds preventing mitochondrial dysfunction as a possible treatment for Parkinson's disease.

Marseille, France-based Trophos specializes in the discovery and development of drugs for neurological disorders and has discovered two compounds that arrest or prevent early Parkinson's-like behavioral changes observed in a preclinical model overexpressing human alpha-synuclein.

Mutations in alpha-synuclein are known to cause familial Parkinson's, and the protein accumulates in affected neurons in sporadic forms of the disease.

Trophos will undertake the project in collaboration with a research team at UCLA headed by Marie-Françoise Chesselet, which has studied the model extensively. Chesselet is the Charles Markham Professor of Neurology at UCLA and chair of the department of neurobiology. She is a recognized expert on the biology of central nervous system (CNS) diseases such as Parkinson's.

Parkinson's is a multifaceted pathology, characterized by, among other things, the death of brain dopaminergic neurons that are essential for controlling movement. Trophos pointed out that, while the exact cause of the disease is not known, evidence suggested that mitochondrial malfunction occurs in stressed dopaminergic neurons. Several environmental toxins that produce symptoms remarkably like Parkinson's and several genes associated with familial Parkinson's lead to mitochondrial malfunction.

The team at UCLA has documented early Parkinson's-like behavioral changes in the preclinical model over-expressing human alpha-synuclein. For its part, Trophos has identified a family of compounds that enhance the survival of motor neurons in models of motor neuron degeneration. Those compounds bind to mitochondrial proteins and thus maintain mitochondrial function in cells subjected to various types of stress.

The two Trophos compounds to be studied have been extensively characterized, and one of them, TRO19622, already has demonstrated a good safety profile in a Phase I clinical trial. If either compound shows potential therapeutic benefit in the Parkinson's model, it could progress to clinical testing in patients with Parkinson's.

"Evidence that a Trophos compound that targets mitochondria has a beneficial effect could establish a new therapeutic approach to the treatment of Parkinson's and potentially other neurodegenerative diseases," noted the company's CSO, Rebecca Pruss.

At The Michael J. Fox Foundation, CEO Katie Hood stressed the importance of the initiative in helping firms to "optimize and advance the most promising treatments that might otherwise get stuck at the preclinical stage for lack of funding. The grant to Trophos is an excellent example of how our capital, while comparatively modest, can serve as a carrot to leverage companies' expertise and infrastructure and speed the development of treatments that could have an immense impact on patients' quality of life."