A Dose Escalation, Proof of Concept, Phase IIa Study to Investigate the Safety and Tolerability, the Pharmacokinetic and the Pharmacodynamic of BN82451B, Administered Twice Daily Over 4 Weeks, in Male Patients With Huntington's Disease

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BN82451B versus placebo after oral administration twice daily (bid) for 28 days in patients with Huntington's Disease (HD).

Start Date01 Sep 2014

Sponsor / Collaborator

Ipsen SA

100 Clinical Results associated with BN-82451

100 Translational Medicine associated with BN-82451

100 Patents (Medical) associated with BN-82451

Literatures (Medical) associated with BN-82451

01 Mar 2011·NeuropharmacologyQ2 · MEDICINE

BN82451 attenuates l-dopa-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson’s disease

Q2 · MEDICINE

Article

Author: Ferrandis, Eric ; Grandoulier, Anne Sophie ; Auguet, Michel ; Chabrier, Pierre-Etienne ; Rocher, Marie Noelle ; Marin, Jean-Gregoire ; Mautino, Gisele ; Spinnewyn, Brigitte

The development of L-dopa-induced dyskinesia (LID) remains a major problem in the long-term treatment of Parkinson's disease (PD). This study aimed to assess the effect of the multitargeting molecule BN82451 on LID and to measure striatal mRNA expression of several genes in a rat model of PD. Rats were administered two unilateral injections of 6-OHDA in the striatum. After four weeks, the animals started a chronic daily treatment with increasing doses of L-dopa over a further four-week period. Over the course of L-dopa treatment, the rats developed abnormal involuntary movements (AIMs) classified as locomotive, axial, orolingual and forelimb dyskinesia. In animals rendered dyskinetic by L-dopa, administration of BN82451 at doses ranging from 1 to 10 mg/kg p.o. attenuated the severity of fully-established AIMs in a dose-related manner. This anti-dyskinetic effect could be achieved with lower doses of BN82451 administered sub chronically vs. acute single treatment. The improvement of AIMs is not due to a reduction in the general motor activity of dyskinetic rats. BN82451 treatment significantly reversed the overexpression of c-Fos, FosB and Arc mRNA associated with the dyskinesiogenic action of L-dopa. A significant correlation between the degree of overexpression of c-Fos, FosB and Arc mRNA and the dyskinesiogenic action of L-dopa was observed. The data demonstrate that BN82451 effectively attenuates LID and the associated molecular alterations in an animal model of PD and may represent a treatment option for managing dyskinesia.

01 Sep 2007·CNS Drug Reviews

Pharmacological Properties of BN82451: A Novel Multitargeting Neuroprotective Agent

Review

Author: Pierre Etienne Chabrier ; Michel Auguet

ABSTRACTBN82451 belongs to a new family of small molecules designated as multitargeting or hybrid molecules. BN82451 is orally active, has good central nervous system penetration, and elicits potent neuronal protection and antiinflammatory properties. Neuronal protection is due to Na+ channel blockade, antioxidant properties, and mitochondria‐protecting activity, whereas inhibition of cyclooxygenases is mostly responsible for its antiinflammatory activity. BN82451 has been shown to exert a potent neuroprotective effect in various in vitro and in vivo animal models. BN82451 was found to exert a significant protection in experimental animal models mimicking aspects of cerebral ischemia, Parkinson disease, Huntington disease, and more particularly amyotrophic lateral sclerosis. Collectively, its pharmacological properties designate BN82451 as a promising neuroprotective agent.

01 Jul 2003·Journal of NeurochemistryQ2 · MEDICINE

Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's disease

Q2 · MEDICINE

Article

Author: Gabrielle Gardian ; Pierre Etienne Chabrier ; Peter Klivenyi ; Robert J. Ferrante ; M. Flint Beal ; Susan Browne

AbstractThere is substantial evidence that excitotoxicity and oxidative damage may contribute to Huntington's disease (HD) pathogenesis. We examined whether the novel anti‐oxidant compound BN82451 exerts neuroprotective effects in the R6/2 transgenic mouse model of HD. Oral administration of BN82451 significantly improved motor performance and improved survival by 15%. Oral administration of BN82451 significantly reduced gross brain atrophy, neuronal atrophy and the number of neuronal intranuclear inclusions at 90 days of age. These findings provide evidence that novel anti‐oxidants such as BN82451 may be useful for treating HD.

100 Deals associated with BN-82451

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Indication	Highest Phase	Country/Location	Organization	Date
Huntington Disease	Phase 2	DE	Ipsen SA	01 Sep 2014
Parkinson Disease	Phase 2	FR	Ipsen SA	-

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