Paul, this is abstracted from :
htt://www.SIBIA/technology.html
Sibia is in early stage, but very promising biotech comp. Visit their web-page and you will learn a lot about CNS/disease.
mz
xxxxxx
The Role of Calcium in CNS Function and Disease
The human central nervous system is a complex network of interconnected nerve cells, known as
neurons, that are responsible for coordination of virtually all bodily functions, including movement
and sensory perception, learning, memory and decision making. Neurons receive, conduct and
transmit signals. Communication between neurons is essential to the function of the central nervous
system. Dysfunction of neurons and/or communications between neurons can result in neurological
disorders (e.g., epilepsy), psychiatric disorders (e.g., schizophrenia and depression) and
neurodegenerative disorders (e.g., Alzheimer's and Parkinson's diseases).
Communication between neurons occurs through complex electrical and chemical processes.
Neurons communicate with each other and with target cells through the transmission and reception
of molecules known as neurotransmitters. Nerve impulses in the form of voltage changes cause the
release of neurotransmitters from one neuron, which then activate specific receptors on the surface
of an adjacent neuron or target cell and cause a response in the receiving cell. Each different
neurotransmitter interacts with a specific corresponding receptor or family of receptors and
transmits primary messages between neurons that control important processes within those neurons.
These processes include the regulation of secondary messenger systems that, in turn, modulate a
wide array of signal transduction pathways involved in neuronal communication and survival.
Calcium ions are one of the most important primary and secondary messengers in the nervous
system. Calcium ions enter neurons through ion channels ("receptor/ion channels") which open and
close (i.e., are gated) either through ligand/receptor interactions or voltage changes such as nerve
impulses. These receptor/ion channels regulate many essential functions in neurons, such as the
release of neurotransmitters, electrical activity, activation of enzymes and transcription of genes. The
diagram below illustrates the fundamental mechanism of communication between adjacent neurons
and the role of calcium ions in that process.
Because calcium is central to so many critical neuronal functions, the Company has identified the
control of calcium levels within neurons as a key strategy for potential therapeutic intervention in
many CNS disorders, including stroke, epilepsy, pain, Parkinson's disease and Alzheimer's disease
and other dementias. For example, the lack of blood flow and oxygen deprivation caused by a
stroke results in abnormally high concentrations of the neurotransmitter glutamate, triggering a
subsequent influx of excessive calcium ions through specific receptor/ion channels into neurons. This
leads to neuronal cell death and brain damage. Drugs that block the abnormal release or action of
glutamate and/or the excessive calcium buildup in the neurons could represent effective stroke
therapies. Another example of the role of calcium in CNS disorders can be seen in Parkinson's
disease. The motor deficits associated with Parkinson's disease are the result of abnormally reduced
levels of the neurotransmitter dopamine, the release of which is calcium-mediated. Drugs that
activate specific receptor/ion channels to enhance the calcium-mediated release of dopamine from
neurons could ameliorate the motor dysfunction in Parkinson's disease patients.
Over approximately the past 20 years, drugs blocking calcium influx through certain receptor/ion
channels have been successfully developed and commercialized for the treatment of cardiovascular
diseases such as angina and hypertension. However, these existing calcium channel blockers have
been either ineffective or have significant side effects when evaluated for CNS disorders. This is
likely due to their lack of selectivity or activity on specific neuronal subtypes, which is typical of
compounds identified by traditional drug discovery approaches. The Company believes that its
technologies will permit the targeted identification of compounds that are selective for specific
receptor/ion channel subtypes, enabling the discovery and development of new classes of drugs that
could be more effective and have fewer side effects than existing drugs for the treatment of CNS. |
