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Sigma ligands for neuronal regeneration and functional recovery

A neuronal, neurodegenerative technique applied in the field of neuronal regeneration

Inactive Publication Date: 2008-09-24
MS SCI CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] However, in addition to the role of environmental factors on brain plasticity, drugs and drug-environmental interactions are another aspect to consider

Method used

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  • Sigma ligands for neuronal regeneration and functional recovery

Examples

Experimental program
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Effect test

example 1

[0119] Animal Models of Neuronal Regeneration (Functional Restoration)

[0120] Male 3-month-old SHR (spontaneously hypertensive) rats were used to induce MCA-occlusive stroke. This is the preferred category since most stroke patients are hypertensive. Animals were anesthetized with Methohexital and a small craniotomy was performed on the zygmotic arch to expose the middle cerebral artery, which was occluded with 10-0 monofilament nylon suture distal to the origin of the striatal branches . Rats were not intubated and no catheters were inserted. Following MCA occlusion, massive and reproducible infarcts were obtained, resulting in a lack of robust sensory activity. Animals were placed on a 6 hour light / 18 hour dark cycle without food or water. Two days after MCAO, rats were treated with Compound I, II, III, IV, V, VI, VII, VIII or IX (0.03-10 mg / kg) s.c. or p.o. and a control group was given saline for 2-8 weeks. Animals were tested at 2, 4, 6 and 8 weeks in either the ...

example 2

[0134] Evidence of nerve regeneration in rats treated with SA4503

[0135] 1. Rotating rod

[0136] Thirty-five spontaneously hypertensive rats were exposed to constant middle cerebral artery occlusion (MCAO) and then divided into three treatment groups. SA4503 was administered s.c. at a dose of 0.3 mg / kg (12 rats) or 1.0 mg / kg (12 rats) starting two days after occlusion and continuing daily up to 28 days after occlusion. In the control group (11 rats), only vehicle was administered. At several time points after the initiation of treatment and during testing, rats were assessed for their ability in the rotarod model. Such a model is described in Example 1. It requires rats to pass through a horizontally suspended rotating rod with a length of 1 m. This task measures the sensory-motor abilities of animals. The behavior of the animals is recorded using video cameras and then analyzed and scored by specially trained technicians. Scores range from 0-6, with 0 indicating the ...

example 3

[0148] Gene Expression Studies

[0149] The Ethics Committee for Animal Research at Lund University approved the protocol. Six-month-old male SHR (550 x 350 x 200 mm, 3 to 4 rats per cage) were housed in standard cages (550 x 350 x 200 mm, 3 to 4 rats per cage) for the first 2 months and before surgery, obtained from Mollegard Breeding Center, Ejby, Denmark. Spontaneously hypertensive rats) were anesthetized intraperitoneally with methohexital sodium (Brietal, 37° C.) 50 mg / kg. The right MCA was assessed via a minicraniotomy and the artery was ligated at the terminal end of the striatal artery to cause neocortical infarction. The average procedure time was about 20 minutes and body temperature was maintained close to 37°C. After surgery, rats were kept in individual cages for 24 hours. Rats subjected to MCA occlusion (MCAO) were transferred to a standard environment (SE), or placed into large, vertical enriched environment (EE) cages (815 x 610 x 1,280 mm) equipped with hor...

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Abstract

The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably SA-4503, or salts, or solvates thereof These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by ischemic stroke, diabetic peripheral neuropathy, cancer therapy induced neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, Huntington's disease or Parkinson's disease. In other methods, the sigma receptor ligands are administered after stroke to facilitate functional recovery. The administration of the sigma receptor ligands effects faster functional recovery.

Description

[0001] Cross References to Related Applications [0002] This application asserts U.S. Provisional Patent Applications 60 / 478,735, filed June 12, 2003, 60 / 478,329, filed June 12, 2003, and 60 / 498,132, filed August 26, 2003 and 60 / 552,613 filed March 12, 2004, all of which references are hereby incorporated by reference in their entirety. technical field [0003] The present invention relates to methods of treatment to achieve neuronal regeneration in a subject having a neurodegenerative disorder. In particular, the present invention relates to the use of sigma receptor ligands to promote neuronal regeneration and functional recovery in a subject following a neurodegenerative disease. Background technique [0004] Martin et al. (1976) J. Pharmacol. Exp. Ther. 197 : 517-532 mention the presence of sigma receptor ligands to explain the psychotomimetic effects of benzomorphan. Sigma receptors were initially considered to be novel opioid receptors. However, the binding of be...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61K31/485A61K31/195A61P25/00
Inventor 唐娜·奥克森伯格罗曼·厄弗
Owner MS SCI CORP
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