Amit Kumar1,2, Tomoko Kitago3,4. 1. Burke Neurological Institute, 785 Mamaroneck Ave., White Plains, NY, 10605, USA. 2. Weill Cornell Medicine, New York, NY, USA. 3. Burke Neurological Institute, 785 Mamaroneck Ave., White Plains, NY, 10605, USA. tok7002@med.cornell.edu. 4. Weill Cornell Medicine, New York, NY, USA. tok7002@med.cornell.edu.
Abstract
PURPOSE OF REVIEW: This review aims to discuss the recent literature relating to drugs for stroke recovery and to identify some of the challenges in conducting translational research for stroke recovery. RECENT FINDINGS: Advances in our understanding of neural repair mechanisms in pre-clinical stroke models have provided insights into potential targets for drugs that enhance the repair/recovery process. Few drugs that act on serotonergic and dopaminergic systems have been tested in humans with mixed results. The FOCUS trial, a phase III study of early administration of fluoxetine for stroke recovery, failed to replicate the promising results of the FLAME trial, but outcome measures differed between the two trials. Another drug that has recently been shown to have potential to promote motor recovery after stroke is maraviroc, an inhibitor of C-C chemokine receptor 5 that is involved in learning and memory. Various drugs, including modulators of neurotransmitters, axonal growth inhibitor blockers, and growth factors, have been examined in preclinical and clinical studies for their ability to promote neural repair, particularly in the motor system. Neuroplasticity, broadly defined as the capacity of the brain to undergo biochemical, structural, or functional changes, is heightened early after stroke when behavioral improvements are observed. Further studies are needed to determine which of these neuroplastic processes are causal to recovery and therefore appropriate targets for drugs to promote recovery. There has also been little focus on trying to distinguish processes that promote true behavioral recovery versus those that improve task success through use of compensatory strategies. Incorporation of sensitive and detailed outcome measures that assess movement quality as well as task success in both preclinical and clinical studies are needed to further elucidate appropriate drug targets and improve the translation of preclinical findings into successful clinical trials.
PURPOSE OF REVIEW: This review aims to discuss the recent literature relating to drugs for stroke recovery and to identify some of the challenges in conducting translational research for stroke recovery. RECENT FINDINGS: Advances in our understanding of neural repair mechanisms in pre-clinical stroke models have provided insights into potential targets for drugs that enhance the repair/recovery process. Few drugs that act on serotonergic and dopaminergic systems have been tested in humans with mixed results. The FOCUS trial, a phase III study of early administration of fluoxetine for stroke recovery, failed to replicate the promising results of the FLAME trial, but outcome measures differed between the two trials. Another drug that has recently been shown to have potential to promote motor recovery after stroke is maraviroc, an inhibitor of C-C chemokine receptor 5 that is involved in learning and memory. Various drugs, including modulators of neurotransmitters, axonal growth inhibitor blockers, and growth factors, have been examined in preclinical and clinical studies for their ability to promote neural repair, particularly in the motor system. Neuroplasticity, broadly defined as the capacity of the brain to undergo biochemical, structural, or functional changes, is heightened early after stroke when behavioral improvements are observed. Further studies are needed to determine which of these neuroplastic processes are causal to recovery and therefore appropriate targets for drugs to promote recovery. There has also been little focus on trying to distinguish processes that promote true behavioral recovery versus those that improve task success through use of compensatory strategies. Incorporation of sensitive and detailed outcome measures that assess movement quality as well as task success in both preclinical and clinical studies are needed to further elucidate appropriate drug targets and improve the translation of preclinical findings into successful clinical trials.
Authors: Michelle Aarts; Yitao Liu; Lidong Liu; Shintaro Besshoh; Mark Arundine; James W Gurd; Yu-Tian Wang; Michael W Salter; Michael Tymianski Journal: Science Date: 2002-10-25 Impact factor: 47.728
Authors: J Pariente; I Loubinoux; C Carel; J F Albucher; A Leger; C Manelfe; O Rascol; F Chollet Journal: Ann Neurol Date: 2001-12 Impact factor: 10.422