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Cystamine and analogues for the treatment of Parkinson's disease

Parkinson’s disease is an important neurodegenerative disorder for which there is no curative treatment. Current therapeutic options can, at best, manage certain clinical symptoms.

Prof Francesca Cicchetti and her team have accumulated evidence suggesting that cystamine (and its metabolite cysteamine), a molecule with anti-inflammatory and anti-apoptotic properties, has potent effects against various aspects of Parkinson's disease. They have shown that cystamine and cysteamine can halt or reverse neurodegenerative processes in toxin-induced animal models, and that cystamine can cross the blood-brain-barrier, a clinically-relevant feature given the rarity of drugs with such properties.

Cystamine has been reported to inhibit tranglutaminase, an enzyme contributing to the formation of insoluble protein aggregates that have been observed in the brains of patients with Parkinson's, as well as Alzheimer's and Huntington’s diseases.

References

  • Cicchetti F, C Rouillard, and F Calon (2012-2017). Cystamine analogues for the treatment of Parkinson's disease. WO2012113079A1, CA2732440C, CN103442704A, AU2012220314B2, MX350195B, EP2678009B1, JP6000985B2, RU2630583C2. Assignee: Université Laval.

  • Bousquet M, C Gibrat, M Ouellet, C Rouillard, F Calon, and F Cicchetti. (2010). Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases. J Neurochem 114: 1651-1658.

  • Gibrat C and F Cicchetti (2011). Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 35: 380-389.

  • Tremblay ME, M Saint-Pierre, E Bourhis, D Lévesque, C Rouillard, and F Cicchetti (2006). Neuroprotective effects of cystamine in aged parkinsonian mice. Neurobiol Aging 27: 862-870.

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Opportunities

Cystagon® (cysteamine bitartrate) is marketed in Europe and in the United States for the treatment of nephropathic cystinosis, but patient compliance with orally-administered Cystagon® is sometimes challenging due to gastrointestinal adverse effects.

SOVAR and Université Laval are seeking for a partner for chemical derivation of cystamine/cysteamine, co-development of compounds or formulations better tolerated by mice and humans, licensing, or commercialization of this technology.

Availables resources

The laboratory of Prof Cicchetti is fully capable of performing in vitro, in vivo (in mice and rats), and neurobehavioral evaluation of compounds in animal models of Parkinson's disease.