Neurotrophic factors are under investigation for the treatment of peripheral neuropathies. This article reviews the development of neurotrophic factors for diabetic neuropathy, antineoplastic agents—induced neuropathy, and inflammatory neuropathies. Although there is a good rationale for the use of neurotrophic factors in peripheral neuropathies, many clinical trials have failed to show significant improvement. Administration of neurotrophic factors by gene therapy has shown more favorable results in animal models, but no clinical trials using this method are planned.
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• Neurotrophic factors play an important role in the survival and maintenance of neurons.
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• There are considerable experimental data on various neurotrophic factors in relation to peripheral neuropathies, which forms the basis of therapeutic interventions.
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• There is some evidence of efficacy of neurotrophic factors in diabetic neuropathy in clinical trials and in anticancer agent-induced peripheral neuropathy, but no further clinical trials in are progress.
Historical note and terminology
A trophic factor can be generally defined as any molecule that supports the survival of neurons. Nerve growth factors are polypeptides that regulate the proliferation, survival, migration, and differentiation of cells in the nervous system. Most of the studies have focused on the effect of growth factors on neuronal survival and maintenance, hence, the term “neurotrophic factor.” A neurotrophic factor is synthesized by, and released from, target cells of the neurons, bound to specific receptors, then internalized and transported by retrograde axonal transport to the cell soma where multiple survival-promoting effects are initiated.
Cytokines have also been found to modulate neuronal processes. Originally, they were considered to be derived solely from the cells of the immune system, but now they are known to be produced by the cells of the CNS also. In this article, the term “neurotrophic factors” will be used in a broad sense to cover neurotrophins (nerve growth factor, brain-derived neurotrophic factor, neurotrophins), growth factors, and other substances that promote survival and repair of the cells of the nervous system.
Peripheral neuropathies are likely to be the first group of neurologic disorders to be successfully treated with growth factors because peripheral nerves are accessible to proteins given systemically. The successful use of growth factors in the treatment of peripheral neuropathies may provide the first true therapy for this previously untreatable and devastating group of neurologic disorders.
More than 100 causes of peripheral neuropathies are known. Emphasis in this article will be on the two types that are most relevant to neurotrophic factors: diabetic neuropathy and antineoplastic agent-induced neuropathies. HIV peripheral neuropathy and compressive neuropathies, such as carpal tunnel syndrome, are also amenable to neurotrophic factor therapy.