Method for regulating neuron development and maintenance

Abstract

The present invention relates to a method for regulating neuron development/maintenance and/or regeneration in a nervous system of a mammal and to pharmaceutical compositions comprising leukaemia inhibitory factor useful for same.

1 . A method for regulating neuron development and/or regeneration and/or maintenance in a mammal comprising administering to said mammal an effective amount of leukaemia inhibitory factor (LIF) for a time and under conditions sufficient to permit the development of neural precursor cells into neurons and/or to promote survival of said neural precursor cells.  
   
   
       2 . The method according to  claim 1  wherein the neurons are located in the peripheral nervous system.  
   
   
       3 . The method according to  claim 1  wherein the neurons are located in the central nervous system.  
   
   
       4 . The method according to any one of the preceeding claims wherein the mammal is a human.  
   
   
       5 . The method according to  claim 4  wherein the route of administration is by intravenous or intramuscular injection or infusion or by gene therapy or by retrograde labelling.  
   
   
       6 . The method according to  claim 5  wherein the LIF is mammalian LIF.  
   
   
       7 . The method according to  claim 6  wherein the mammalian LIF is mouse, rat, human or livestock animal LIF.  
   
   
       8 . The method according to  claim 7  wherein the mammalian origin of LIF and the mammal to be treated belong to the same species.  
   
   
       9 . The method according to any one of the preceding claims wherein the effective amount of LIF is from about 0.01 to about 10,000 μg/kg body weight.  
   
   
       10 . The method according to  claim 9  further comprising the simultaneous or sequential administration of one or more other neuron stimulating factors.  
   
   
       11 . The method according to  claim 10  wherein the other neuron stimulating factors comprise FGF, CNTF, NGF and/or BNDF and/or one or more neurotrophic factors.  
   
   
       12 . The method according to  claim 11  wherein each other neuron stimulating factor is administered in an effective amount of from about 0.01 to about 10,000 μg/kg body weight.  
   
   
       13 . The method according to  claim 2  wherein the neurons are sensory neurons.  
   
   
       14 . The method according to  claim 1  or  3  wherein the neurons are spinal cord neurons.  
   
   
       15 . A method for regulating spinal cord development and/or repair and/or maintenance and/or regeneration in a mammal comprising administering to said mammal an effective amount of LIF for a time and under conditions sufficient or to increase the number, to maintain or regenerate spinal cord neurons and/or neurite processes.  
   
   
       16 . The method according to  claim 15  wherein the mammal is a human.  
   
   
       17 . The method according to  claim 15  or  16  wherein the route of administration is by intravenous or intramuscular injection or infusion or by gene therapy or by retrograde labelling.  
   
   
       18 . The method according to  claim 17  wherein the LIF is mammalian LIF.  
   
   
       19 . The method according to  claim 18  wherein the mammalian LIF is mouse, rat, human or livestock animal LIF.  
   
   
       20 . The method according to  claim 19  wherein the mammalian origin of LIF and the mammal to be treated belong to the same species.  
   
   
       21 . The method according to any one of  claims 15  to  20  wherein the effective amount of LIF is from about 0.01 to about 10,000 μg/kg body weight.  
   
   
       22 . The method according to  claim 21  further comprising the simultaneous or sequential administration of one or more other neuron stimulating factors.  
   
   
       23 . The method according to  claim 22  wherein the other neuron stimulating factors comprise FGF, CNTF, NGF and/or BNDF and/or one or more neurotrophic factors.  
   
   
       24 . The method according to  claim 23  wherein each other neuron stimulating factor is administered in an effective amount of from about 0.01 to about 10,000 μg/kg body weight.  
   
   
       25 . A method of treating a disease and/or injury to a nervous system in a mammal comprising administering to said mammal an effective amount of LIF for a time and under conditions sufficient to ameliorate the disease and/or injury.  
   
   
       26 . The method according to  claim 25  wherein the mammal is a human.  
   
   
       27 . The method according to  claim 26  wherein the nervous system is the peripheral nervous system.  
   
   
       28 . The method according to  claim 26  wherein the nervous system is the central nervous system.  
   
   
       29 . The method according to  claim 27  or  28  wherein the disease or injury is Cerebral Palsy, trauma induced paralysis, vascular ischaemia associated with stroke, neuronal tumours, motorneuron disease, Alzheimer's disease, multiple sclerosis, Parkinson's disease, Huntington's disease, peripheral neuropathies associated with diabetes, heavy metal or alcohol toxicity, renal failure and/or infectious disease.  
   
   
       30 . The method according to  claim 29  wherein the infectious diseases comprise herpes, rubella, measles, chicken pox, HIV and/or HTLV-1.  
   
   
       31 . The method according to any one of  claims 25  to  30  wherein the LIF is mammalian LIF.  
   
   
       32 . The method according to  claim 31  wherein the mammalian LIF is mouse, rat, human or livestock animal LIF.  
   
   
       33 . The method according to  claim 32  wherein the mammalian origin of LIF and the mammal to be treated belong to the same species.  
   
   
       34 . The method according to  claim 26  or  30  wherein the effective amount of LIF is from about 0.01 to about 10,000 μg/kg body weight.  
   
   
       35 . The method according to  claim 34  further comprising the simultaneous or sequential administration of one or more other neuron stimulating factors.  
   
   
       36 . The method according to  claim 35  wherein the other neuron stimulating factors comprise FGF, CNDF, NGF and/or BNDF and/or one or more other neurotrophic factors.  
   
   
       37 . A pharmaceutical composition comprising LIF, one or more other neuron stimulating factors and one or more pharmaceutically acceptable carriers and/or diluents.  
   
   
       38 . The pharmaceutical composition according to  claim 37  wherein the neuron stimulating factors comprise FGF, CNDF and/or BNDF and/or one or more other neurotrophic factors.  
   
   
       39 . The use of LIF in the manufacture of a medicament for the regulation of neurons and/or treatment of diseases or injury to a nervous system in a mammal.  
   
   
       40 . The use according to  claim 39  wherein the nervous system is the peripheral nervous system, the central nervous system and/or the spinal cord.  
   
   
       41 . The use according to  claim 39  or  40  further comprising the use of one or more other neuron stimulating factors.  
   
   
       42 . The use according to  claim 41  wherein the other neuron stimulating factors comprise FGF, CNTF and/or BNDF and/or one or more other neurotrophic factors.