Use of protein S-100-b in medicines containing the protein S-100

Details Use of protein S-100-b in medicines containing the protein S-100 Use of protein S-100-b in medicines containing the protein S-100

1998-04-15

1999-11-23

Davenport, Avis M.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

514 12, 530300, 530324, 424400, A10N 3718, A61K 3800, C07K 500, C07K 700

Patent

active

059900806

DESCRIPTION:

BRIEF SUMMARY
AREA OF THE INVENTION

The present invention concerns the use of a protein S100-b in medicines which aim at stimulating the growth of as well as survival of damaged neurons by primarily the administration of a medicine containing this protein via infusion or injection locally to the damaged region.


BACKGROUND OF THE INVENTION
Rhombencephalon
Peripheral nerves and cranial nerves as well as the spinal cord constitute a functional unit which is responsible for the movements of the body. The unit includes also sensory impulses to the cerebrum and the cerebellum. When undamaged, the unit provides information directed inwards and outwards which is a prerequisite for our daily life.
Each neuron consists of a cell body (perikaryon or soma) as well as two types of processes, one which receives information (dendrites) and one which delivers information (axon) as electrical impulses. The axons of peripheral nerves and cranial nerves are contained within Schwann cells which produce myelin, an insulating lipid-rich material which isolates each axon from the others. In the spinal cord and the rhombencephalon, oligodendroglial cells surround the axons and form the myelin sheaths. In addition, other cell types, such as astrocytes and microglial cells, are present in the spinal cord.
Astrocytes make up 50-70% of the volume occupied by glial cells in the brain. They maintain the microenvironment of the neurons. The microglial cells are much fewer. They are activated during damage to the brain and phagocytize dead material. Furthermore, they play a key role in the immune system of the brain.
The peripheral nerves are made up of axons which mediate impulses to the muscles which in turn cause contractions (motor axons) and axons which mediate information from muscle spindles, tendons joint capsules and the skin (sensory axons). The motor axons are the processes from large perikarya localized in the anterior horns of the spinal cord. The sensory axons have their perikarya in the dorsal root ganglia where they are surrounded by satellite glial cells. The sensory neurons in the spinal cord transfer the information further to the cerebellum and cerebrum.
The neuronal perikarya of the spinal cord are organized as grey matter which, in the cross section, is shaped like an H. This is surrounded by white matter which contains axons travelling up or down.
Ten out of the twelve cranial nerves have their perikarya located in groups (nuclei) within the rhombencephalon. The cranial nerves have either a motor or a sensory function.


REACTION TO DAMAGE

Damage to brain tissue leads to an inflammatory response which is characterized by a vascular response as well as a cellular response, both aiming at defending the body against foreign substances and to dispose of dead and dying tissue. The inflammation per se also prepares the tissue for the process of repair. If axons are sewered, their peripheral parts consistently degenerate. The proximal portions of certain axons, as well as their perikarya degenerate as well and die.
The magnitude of the inflammatory and degenerative processes depends on the size of the damage, the condition of the tissue, as well as on the capacity of the body to provide a response. The primary sign of initiation of the repair process is the growth of axons from surviving perikarya and the elongation of surviving proximal portions of axons. These axons grow through the damaged region and into the sheaths of the degenerated distal part of the nerve or into the spinal cord. This process is slow (a few millimeters per day) and the result of it is uncertain, since the target organs (muscles, blood vessels, skin, tendons, joints, cartilage, bone) which have not received nerve pulses for some time, tend to degenerate prior to the arrival of the growing axons. This leads to a reduced muscle power or paralysis as well as reduced sensory information which indeed constitutes a severe handicap for the affected individual. This type of damage is a considerable socioeconomic drawback also for the society.
Two principal types of

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