Transport protein which is used to introduce chemical compounds into nerve cells
The invention relates to a transport protein which can be obtained by modifying the heavy chain of the neurotoxin formed by Clostridium botulinum . The protein binds specifically to nerve cells with a higher affinity as the native neurotoxin. The invention also relates to a method for the production of transport protein, the nucleic acids coding for the transport protein, the transport protein containing pharmaceutical and cosmetic compositions and use thereof.
1. A transport protein, obtained by modification of the heavy chain of a Clostridium botulinum type A (BoNT/A), said heavy chain comprising a H N -fragment and a H C -fragment, wherein the H C fragment corresponding to amino acids 867-1296 of Clostridium botulinum neurotoxin type A (BoNT/A) protein sequence of SEQ ID NO: 1, 14, 15 or 16 is substituted by a H C fragment corresponding to amino acids 866-1291 of Clostridium botulinum neurotoxin type B (BoNT/B) protein sequence of SEQ ID NO: 17, 18, 19, 20, 21, or 22.
2. The transport protein according to claim 1 , wherein the protein binds specifically to motor neurons and enters the cells by endocytosis.
3. The transport protein according to claim 1 , wherein the protein binds specifically to complex gangliosides of cholinergic motor neurons, localised in the plasma membrane.
4. The transport protein according to claim 3 , wherein the complex gangliosides of cholinergic motor neurons is GT1 b.
5. The transport protein according to claim 1 , wherein the protein exhibits a binding affinity to a motor neuron at least 15% higher than native Clostridium botulinum type A.
6. The transport protein according to claim 1 , wherein said transport protein binds to a nerve cell with a higher affinity than native Clostridium botulinum type A.
7. A composition comprising the transport protein according to claim 1 , wherein said transport protein is coupled to a clostridial neurotoxin protease.
8. The composition according to claim 7 , wherein the clostridial neurotoxin protease includes a Clostridium botulinum neurotoxin protease selected from Clostridium botulinum type A, B, C 1 , D, E, F and G.
9. A method for treating a disorder or disease for which a therapy with botulinus neurotoxin is indicated, said method comprising administration of an effective amount of the composition according to claim 7 .
10. The method according to claim 9 , wherein the disorder or disease is one of the following: hemi-facial spasm, spasmodic torticollis, spasticities, dystonias, migraine, pain, disorders of the neck and lumbar vertebral column, strabism, and hypersalivation.
11. A method for treating a cosmetic indication selected from hyperhidrosis and pronounced facial wrinkles, said method comprising administration of an effective amount of the composition according to claim 7 .