Rho kinase (ROCK) has recently emerged as a novel therapeutic target for neurodegenerative disorders. Levels of ROCK increase with age and tissue of ALS patients show increased levels of ROCK as well as its downstream targets LIMK1 and cofilin. Inhibition of ROCK was shown to counteract neurodegenerative processes and to foster neuronal regeneration in different animal models of neurodegenerative disease. Inhibition of ROCK counteracts neuronal apoptosis and axonal degeneration and on the other hand fosters axonal regeneration and modulates microglia activation. The isoquinoline derivative Fasudil was shown to effectively inhibit ROCK and other kinases like PKA, PKG, PKC, and MLCK. Importantly, it significantly prolonged survival, improved motoric function and induced a regenerative response at the neuromuscular junction accompanied by a modulation of microglial activity in the SOD1-G93A mouse model for ALS.
Thus, there is a large and convincing body of preclinical evidence of BRAVYL’s effect on ALS in animal models. Additionally, there is persuasive human data from a compassionate use study in Europe, where three ALS patients were dosed with an intravenous version of BRAVYL for a month. In all three patients, decline in function was attenuated during and one month after fasudil infusions, in one patient breathing capacity increased during treatment, and in one muscle strength increased during treatment.
The aim of the REAL Study (Rho-kinasE for Als Study) is to assess the preliminary safety and efficacy of BRAVYL in patients with ALS. The open label study will enrol 20 patients at up to 10 sites. Subjects will be treated with BRAVYL for 6 months.
New York-based Woolsey Pharmaceuticals is focused on the treatment of rare, neurodegenerative diseases. The company’s lead product is BRAVYL (oral fasudil).
Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia
Contact: Susan Heggie (07) 3646 3111 susan.heggie@health.gld.gov.au
Calvary Health Bethlehem Hospital, Melbourne, VIC 3195, Australia
Contact: Emma Windebank (03) 9596 2853 Emma.Windebank@calvarycare.org.au
Macquarie University Hospital, Sydney, NSW 2109, Australia
Contact: Richard Gan Richard.gan@mq.edu.au
A possible treatment resulting from this study is years away. This research will provide preliminary data to the assess the preliminary safety and efficacy of Fasudil in ALS patients.
