The aging population, combined with new and improved treatments for neurodegenerative disorders such as Alzheimer's and Parkinson's disease will lead to an expansion of the already $30 billion neurodegenerative market.

Parkinson's disease affects some four million people worldwide. It is a progressive disorder of movement characterized by a progressive loss of dopamine neurons in the pars compacta of the substantia nigra and various extrapyramidal features including resting tremor, rigidity, bradykinesia, postural instability, and freezing. The current worldwide market for the treatment of Parkinson's disease is estimated to be approximately $1.5 billion with an estimated annual growth of 10% (click here for “Neurodegenerative Disorders: World Markets 2002-2007” which provides a full analysis of this field ).

The massive activation of poly (ADP-ribose) polymerase-1 (PARP-1) by DNA-damaging stimuli, such as exposure to reactive oxygen species (ROS), can lead to cell injury via severe, irreversible depletion of the NAD and ATP pool, and PARP-1 inhibitors have been expected to rescue neurons from degeneration in a number of disease models.

Fujisawa Pharmaceuticals have recently identified FR255595 as a novel and potent PARP-1 inhibitor through structure-based drug design and high throughput screening. This compound potently inhibited PARP activity and was orally active and highly brain penetrable. The Journal of Pharmacology And Experimental Therapeutics is soon to publish data from researchers at Fujisawa showing that prevention of PARP activation by FR255595 protects against both ROS-induced cells injury in vitro and nigrostriatal dopaminergic damage in an in vivo Parkinson's disease model.

In cell death models in vitro, Iwashita et al report that treatment with FR255595 significantly reduced PARP activation and cell death. In the mouse MPTP model of Parkinson's disease, oral administration of FR255595 reduced MPTP-induced neuronal damage both in the substantia nigra and in the striatum via marked reduction of PARP activation, even with delayed-treatment. These findings clearly indicate that the novel PARP-1 inhibitor FR255595 exerts neuroprotective effect through its potent PARP-1 inhibitory actions, suggesting that the drug could be an attractive candidate for several neurodegenerative disorders including Parkinson's disease.

(source DailyUpdates 8th March; for a full abstract of the original paper see J Pharmacol Exp Ther. 2004 Feb 25 [Epub ahead of print])