Cystamine metabolism and brain transport properties: clinical implications for neurodegenerative diseases

• DOI: 10.1111/j.1471-4159.2010.06874.x
• Publication Date: 2010-06-21T06:46:59Z
• Authors: Mélanie Bousquet; Claire Gibrat; Mélissa Ouellet; Claude Rouillard; Frédéric Calon; Francesca Cicchetti
• Keywords: Cystamine

J. Neurochem. (2010) 114 , 1651–1658. Abstract Cystamine has shown significant neuroprotective properties in preclinical studies of Parkinson’s disease (PD) and Huntington’s (HD). Cysteamine, its FDA‐approved reduced form, is scheduled to be tested for clinical efficacy HD patients. Here, we studied the key cystamine metabolites, namely cysteamine, hypotaurine taurine, as well cysteine, order identify which one more distinctively responsible action cystamine. After a single administration (10, 50 or 200 mg/kg), naïve mice were perfused with phosphate‐buffered saline (PBS) at 1, 3, 12, 24 48 h post‐injection brain plasma samples analyzed by two distinct HPLC methods. Although levels remained under detection threshold, increases cysteamine detected mg/kg doses 1 3 following injection. To further assess candidate molecule pre‐clinical trials PD, evaluated capacity cross blood barrier. Using an situ cerebral perfusion technique, determined that transport coefficient (Clup) (259 μM) was 0.15 ± 0.02 μL/g/s increased up 0.34 0.07 when co‐perfused presence cysteine. Taken together, these results strongly suggest neuroactive metabolite may support therapeutic use neurodegenerative diseases, particularly PD.