Ischemia of nerves or of nervous tissue is generally caused by vascular diseases, e.g. due to embolism or a thrombosis. The nerves of the central nervous system may be effected thereby, e.g. by a cerebral infarction. Ischemia ultimately leads to the necrotic death of the affected tissue.
A traumatic impact may also lead to such a death of the nerves. For example, spinal cord injuries and mechanical lesions of peripheral nerves are known. Moreover, environmental influences due to toxic substances, e.g. heavy metals, may result in a necrosis of nerves.
New therapeutic approaches for such nerve injuries comprise the administration of neurotrophic factors or of neurotrophines to which a significant influence on the survival, growth and differentiation of discrete neuronal populations is ascribed. The neurotrophine family includes nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophine-3 (NT-3), neurotrophine-4 (NT-4) and the CNTF-family (ciliary neurotrophic factor). Neurotrophines are small basic proteins with a molecular weight of 26 to 28 kDa. NGF is the best characterised member of the neurotrophine family which shows activity in many different tissues.
In the peripheral nervous system (PNS) NGF is critical to the development of sympathetic and certain sensory nerves. In the central nervous system (CNS), NGF serves a trophic role in the development and maintenance of cholinergic neurons of the basal forebrain. It also plays a role in adult CNS tissues in neuronal regeneration.
The use of neurotrophic factors for the treatment of postlesional neuronal diseases of e.g. traumatic, ischemic or toxic origin has not attained the expected success up to now.
Particularly in the case of the treatment of nerve injuries in the brain, neurotrophic factors are not suitable since they may not pass the blood-brain barrier and are thus not available for parenteral or enteral administration.
The stimulatory effect on nerve growth required for the treatment of postlesional diseases is to be distinguished from a nootropic effect of substances, as described for example in EP 0 316 218 B1, which is only observed temporarily during administration, but does not provide a permanent nerve regeneration.