Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Primate cell – per se
Patent
1995-10-11
1997-11-25
Rollins, John W.
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Primate cell, per se
435325, C12N 500
Patent
active
056912013
DESCRIPTION:
BRIEF SUMMARY
CROSS-REFERENCE TO RELATED APPLICATIONS
filed Apr. 13, 1994, which claims priority from European Patent Application Serial Nos. 93.201.193.5, filed on Apr. 26, 1993, and 93.201.411.1, filed on May 18, 1993.
The present invention is concerned with the use of sabeluzole for the manufacture of a medicament for the treatment of patients suffering from chronic neuro-degenerative diseases such as dementia of the Alzheimer type (DAT) or Alzheimer's disease, amyotrophic lateral sclerosis (ALS), dementia associated with Parkinson's disease and other central nervous system diseases which are characterized by progressive dementia. Said treatment comprises the administration of sabeluzole in an amount effective in improving, halting, retarding or palliating the course and/or effects of said chronic neurodegenerative diseases. The invention also concerns a method of treating patients suffering from chronic neurodegenerative diseases by administering to said patients an amount of sabeluzole effective in improving, halting, retarding or palliating the course and/or effects of said neurodegenerative diseases. Further there are provided a method of attenuating neuronal cell death in neuronal cells in contact with factors inducing the expression of epitopes associated with aberrantly phosphorylated tau-protein, and a method of inhibiting the formation in neuronal cells of neurofibrillary tangles, which consist mainly of aberrantly phosphorylated tau-protein, said methods comprising contacting said cells with an amount of sabeluzole effective in attenuating said cell death, and in inhibiting the formation of said tangles. The invention also relates to a method of inducing in neuronal cells the expression of epitopes associated with aberrantly phosphorylated tau-protein, which method comprises contacting said cells with a medium conditioned from serum-starved cells for several days and having acquired cytotoxic activity. The invention also concerns a novel polymorph of sabeluzole having improved solubility properties, compositions comprising this novel polymorph and methods for preparing said polymorph and compositions.
In U.S. Pat. No. 4,861,785 there are described compounds having antihypoxic and antianoxic properties useful in indications such as shock, cardiac arrest and severe blood loss. Among these compounds features dineethanol, mp. 101.7 .degree. C., which is generically known as sabeluzole. Subsequent investigations with this compound have shown it to have positive effects on adaptive learning behaviour in animals (Drug Dev. Res., 8, 381-385, 1986) and on memory in humans with suboptimal memory functions (Psychopharmacology, 96, 309-310, 1988; Curr. Ther. Res., 44, 966-974, 1988). The ability of sabeluzole to increase significantly fast axonal transport of submicrometer vesicles in neuronal cells is known from Experimental Neurology, 117, 36-43, 1992. Its accelerating effect on neurite outgrowth is described in Restorative Neurol. Neurosci., 4, 24-32, 1992.
Chronic neurodegenerative diseases are currently the main cause of progressive dementia in elderly people. Among these diseases, dementia of the Alzheimer type (DAT) or Alzheimer's disease is the most prevalent and is estimated to account for about 50% of all severe cases of dementia. Other forms of dementia, inter alia multi-infarct dementia which is due to damage to the nervous system following stroke or brain injury are slightly less common. However, these disorders are often complicated by chronic neurodegenerative diseases. Progressive dementia is characterized by impaired memory, language and visuo-spatial skills and behaviour. The debilitating changes occur over a long term ranging from six up to twenty or more years. Usually, between seven to ten years following onset of the symptoms the patient dies in mental oblivion. Neuropathological features characterizing the brain of people afflicted with Alzheimer's disease are: the brain parenchyma and the wall of the leptomeningeal blood vessels; tangles which accumulate within neurons and in the brain parenchy
REFERENCES:
Geerts et al., "Sabeluzole, a Memory-Enhancing Molecule, Increases Fast Axonal Transport in Neuronal Cell Cultures", Exp. Neurology 117, 36-43 (1992).
Robbins, "Arresting memory decline", Nature, vol. 336, pp. 207-208, 17 Nov. 1988.
De Deyn et al., "Single-dose and steady-state pharmacokinetics of sabeluzole in senile dementia of Alzheimer type patients", Eur. J. Clinical Pharmacology, vol. 43, No. 6, pp. 661-662, 1992.
Werbrouck et al., "Comparison of the In Vivo Pharmacological Profiles of Sabeluzole and Its Enantiomers", Drug Development Research 24:41-51 (1991).
Maloteaux et al., "Progress in Research and Treatment in Regard to Alzheimer's Disease", Louvain Medical, vol. 112(4), pp. 283-288, 1993
Clincke et al., "R 58 736, a Novel Antihypoxic Drug Improves Memory in Rats", Drug Development Research 8:381-385 (1986).
Clincke et al., "Sabeluzole (R 58 735) increases consistent retrieval during serial learning and relearning of nonsense syllables", Psychopharmacology (1988) 96:309-310.
Tritsmans et al., "Memory Study with Sabeluzole in a Population with a Mean Age of 85 Years: A Pilot Experiment", Current Therapeutic Research, vol. 44, No. 6, Dec. 1988, pp. 966-974.
Geerts et al., "Sabeluzole accelerates neurite outgrowth in different neuronal cell lines", Restorative Neurology and Neuroscience, 4 (1992) 21-32.
Clincke Gilbert Henri Camiel
Geerts Hugo Alfons Gabriel
Tritsmans Luc Remi Mathilde
Janssen Pharmaceutica N.V.
Metz Charles J.
Rollins John W.
LandOfFree
Use of sabeluzole in chronic neurodegenerative diseases does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of sabeluzole in chronic neurodegenerative diseases, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of sabeluzole in chronic neurodegenerative diseases will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2106111