Blind World Magazine

Macular Degeneration.
Neurotrophic Factors.

January/February 2005.
Saturday Evening Post - Indianapolis,IN,USA.

A promising area of research is exploring the use of neuroprotective compounds called neurotrophic factors, which represent a new generation of therapeutic agents that can potentially prevent cell death and vision loss in patients with macular degeneration.

For decades, scientists believed that brain cells of the central nervous system could not regrow following damage due to trauma such as head injury or disorders such as Alzheimer's disease. Treatments did not exist. The outlook was bleak.

But now that thinking has been turned upside down. Scientists recently have discovered a whole family of proteins called neurotrophic factors--derived from the Greek "neuro" for nerve and "troph" for nourish. These proteins play a crucial role in the development and survival of nerve cells, or neurons, and in supporting adult neurons to keep them healthy throughout life. Neurotrophic factors also are capable of making damaged neurons regrow their processes in a test tube and in animal models. Because of this, they represent exciting possibilities for reversing devastating brain disorders, including Alzheimer's disease, Parkinson's disease, and Lou Gehrig's disease (amyotrophic lateral sclerosis, or ALS).

Recent research shows that neurotrophic factors are:

Present in early development of the nervous system and are responsible for the initial growth and development of neurons in the peripheral and central nervous systems.

Released by target tissue of a growing neuron and can determine whether a neuron reaches its target during development; neurons which do not reach the target die.

Scientists are now looking for ways to harness neurotrophic factors to induce the regrowth of damaged neurons and improve symptoms of patients with neurological diseases. Neurotrophic factors exert their effects on neurons through several receptors--proteins on the surface of cells into which neurotrophic factors fit much the way a key fits a lock.

Neurotrophic factors, produced by several body tissues (including muscle), act by attaching to receptors on the tips, or nerve terminals, and on the cell body--which contains the nucleus--of neurons. The signal can then be carried through the axon--the neuron's elongated fiberlike extension, which can be as long as a yard--to the cell body, where it tells the cell what to do.

Thus far, scientists have identified several neurotrophic factor receptors--which also may be potential targets for therapy. A receptor called trk is required for the action of nerve growth factor (NGF), the first neurotrophic factor, which was discovered 40 years ago. NGF primarily affects neurons using the neurotransmitter acetylcholine in the basal forebrain, sensory neurons, and sympathetic neurons that regulate organs such as the heart and lungs. Relatives of trk are receptors for other neurotrophic factors--trkB seems to be a receptor for brain-derived neurotrophic factor, and trkC for neurotrophin-3.

Scientists continue to match up various neurotrophic factors and their possible roles in maintaining neurons and in neurological disorders. Meanwhile, ciliary neurotrophic factor, insulin-like growth factor-1, and brain-derived neurotrophic factor are in human clinical trials for treating ALS.

These patients may be among the first to benefit from a therapeutic neurotrophic factor because treatment for ALS does not need to cross the blood-brain barrier. Since ALS involves the loss of motor neurons whose axons are located in the peripheral nervous system, drugs can be delivered by injection. Success with these investigations should encourage scientists to devise treatments for disorders of the central nervous system, such as Parkinson's disease and Alzheimer's disease.

While therapeutic agents made from neurotrophic factors are several years away, research holds tremendous promise. Moreover, dozens of neurotrophic factors may yet be discovered, and these may be important for treating other neurodegenerative disorders and trauma.

End of article.

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