Compositions and methods for promoting neural regeneration

Abstract

The present invention relates to compositions and methods for promoting tissue regeneration, preferably neural tissue regeneration. Compositions of the invention include (i) certain diphenyl sulfides, diphenyl sulfoxides, diphenyl sulfones, and sulfide, sulfoxide and sulfones of dibenzothiophene and thioxanthene, as well as various analogues and derivatives of these compounds; (ii) one or more cells harvested from an animal or organism subsequent to the administration of a composition comprising a compound of (i); or (iii) any combination of (i) and (ii). The invention can be useful in treating decreases in neuronal function, for example from injury or disease.

Description

[0001] The present invention relates to promoting tissue regeneration, such as neural tissue or liver tissue regeneration. More specifically, the present invention employs (i) certain diphenyl sulfides, diphenyl sulfoxides, diphenyl sulfones, and sulfide, sulfoxide and sulfones of dibenzothiophene and thioxanthene. [0002] The nervous system consists essentially of two categories of cells, neurons and glial cells. During neuronal development, immature nerve cell bodies migrate along glial cells to a location in the brain, where neurite processes (dendrites and axons) grow out from the nerve cell body. A growth cone at the tip of each process guides the path taken by each process, determining the path of neuron growth. A number of factors influence the path of neuron growth, including nerve growth factor (NGF) and local contact with cell-cell adhesion molecules, contact with extracellular matrix molecules and various other forms of chemotactic guidance. Cell-cell adhesion molecules th...

AI Technical Summary

Benefits of technology

[0008] Current approaches for treating the loss of neural function that accompanies neuron cell death include the replacement of damaged or dead neural tissue with various transformed cells of neural and non-neural origins, neutralizing the nerve-growth inhibitory properties of various proteins in the CNS environment, as well as introduction of stem cells or progenitor cells.

[0018] In some embodiments, compositions or methods of the invention can treat a neurodegenerative condition or disease such as Parkinson's Disease, Alzheimer's disease, Huntington's Disease, HIV-1 infection, AIDS dementia, amyotrophic lateral sclerosis, stroke, trauma, hereditary hemorrhage with amyloidosis-Dutch type, cerebral amyloid angiopathy, Creutzfeld-Jakob disease or multiple sclerosis, (MS). In some preferred embodiments, the compositions or methods of the invention can treat injury to neural tissue including traumatic injury, or injury to neural tissue resulting from surgery. In some preferred embodiments, the compositions or methods of the invention improve recovery of learning and memory function in a mammal, which untreated mammal has sustained a decrease in or a loss of neuronal function prior to the administration.

Problems solved by technology

Lineage analysis alone, however, does not directly identify the multipotential cells; nor does it define the mechanisms that drive them to different fates.

Much of the adult central nervous system is unable to grow new neurons or generate new axons.

Injuries to neurons involving transection of, or damage to, the axons (termed “axotomy”) characteristically result in retrograde neuronal dysfunction or death to most of these cells.

Such injuries can result, for example, from trauma to the head or spinal cord, or as a consequence of surgical procedures intended to correct certain conditions of the nervous system.

In addition, damage to axons can occur as a result of neurodegenerative disease, excitotoxic injury, or chemotherapy or radiation therapy.

The amount of excitotoxins released increases in response to abnormal conditions (i.e., seizure, hypoglycemia, and the like) and results in neural loss in the areas of concentration.

While transplantation of nervous tissue to the spinal cord has been attempted on animals and has been shown to improve the regeneration after an injury, the functional recovery after such transplantation is often deceptive and improvement of this method is needed before it can be attempted on patients.

For example, considering that neuron growth during development requires stimulation, for example by Nerve Growth Factor (NGF), it is not fully known whether stimulation of the regrowth of mature CNS neurons will be limited by compromised access of neurons to stimulatory mechanisms, in addition to inhibitory proteins in the CNS.

Thus, it is not known whether neutralizing the inhibitory action of certain CNS proteins will adequately promote functional neural regeneration in vivo.

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