Methods of treatment with prosaposin-derived peptides

Abstract

The invention provides a method of alleviating neuropathic pain in a subject by administering a neuropathic pain alleviating amount of prosaposin receptor agonist to the subject. The invention also provides a method of inhibiting the onset of neuropathic pain in a subject by administering neuropathic pain alleviating amount of prosaposin receptor agonist to the subject. The present invention also provides prosaposin receptor agonists and the use of these agonists for stimulating neurite outgrowth, inhibiting neural cell death, promoting myelination and inhibiting neural demyelination. In addition, there is provided a method of inhibiting sensory or motor neuropathy by contacting neuronal cells with a composition comprising an effective inhibiting amount of prosaposin receptor agonist.

1 - 31 . (canceled)  
     
     
         32 . A method of treating a complication of diabetes mellitus comprising administering to a subject diagnosed with diabetes mellitus an effective amount of a composition, wherein the composition comprises a peptide comprising the sequence shown in SEQ ID NO: 2.  
     
     
         33 . The method of  claim 32 , wherein the complication is selected from the group consisting of neuropathy, neuropathic pain and diabetic nerve dysfunction.  
     
     
         34 . The method of  claim 32 , wherein the diabetes mellitus is type I (insulin dependent) diabetes.  
     
     
         35 . The method of  claim 33 , wherein the neuropathy is selected from the group consisting of peripheral neuropathy, sensory neuropathy, polyneuropathy and mononeuropathy.  
     
     
         36 . The method of  claim 33 , wherein the neuropathy comprises a symptom selected from the group consisting of reduced nerve conduction velocity, relacitios, resistance to ischemic block, exaggerated pain response to a painful stimulus and thermal response disorder.  
     
     
         37 . The method of  claim 36 , wherein the nerve is a motor nerve or a sensory nerve.  
     
     
         38 . The method of  claim 37 , wherein the motor nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         39 . The method of  claim 37 , wherein the sensory nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         40 . The method of  claim 36 , wherein the thermal response disorder is selected from the group consisting of thermal hypoalgesia, thermal pain sensation and thermal response latency deficit.  
     
     
         41 . The method of  claim 40 , wherein the thermal response latency is restored.  
     
     
         42 . The method of  claim 36 , wherein a symptom of neuropathy is prevented.  
     
     
         43 . The method of  claim 42 , wherein reduced nerve conduction velocity is prevented.  
     
     
         44 . The method of  claim 40 , wherein thermal hypoalgesia is prevented.  
     
     
         45 . The method of  claim 33 , wherein the neuropathic pain is alleviated.  
     
     
         46 . The method of  claim 33 , wherein the neuropathic pain comprises a symptom selected from the group consisting of hyperalgesia, allodynia, spontaneous pain, pain evoked by light touch and a nerve conduction velocity disorder.  
     
     
         47 . The method of  claim 46 , wherein the hyperalgesia is in response to thermal, mechanical or chemical noxious stimuli.  
     
     
         48 . The method of  claim 46 , wherein the hyperalgesia is reversed.  
     
     
         49 . The method of  claim 46 , wherein the nerve is a sensory nerve.  
     
     
         50 . The method of  claim 46 , wherein the nerve conduction velocity disorder is a decline in sensory nerve conduction velocity.  
     
     
         51 . The method of  claim 50 , wherein the decline in sensory nerve conduction velocity is prevented.  
     
     
         52 . The method of  claim 49 , wherein the progression of an established sensory nerve conduction velocity disorder is halted.  
     
     
         53 . The method of  claim 32 , wherein the administering is selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous, intracranial, epidural, intracerebrospinal, topical, oral, transdermal, transmucosal and transnasal.  
     
     
         54 . The method of  claim 32 , wherein the administering is from the onset of diabetes.  
     
     
         55 . The method of  claim 32 , wherein the administering is after the complications of diabetes are established.  
     
     
         56 . The method of  claim 32 , wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         57 . A method of treating a complication of diabetes mellitus comprising administering to a subject diagnosed with diabetes mellitus an effective amount of a composition, wherein the composition comprises a peptide consisting of the sequence shown in SEQ ID NO: 2.  
     
     
         58 . The method of  claim 57 , wherein the complication is selected from the group consisting of neuropathy, neuropathic pain and diabetic nerve dysfunction.  
     
     
         59 . The method of  claim 57 , wherein the diabetes mellitus is type I (insulin dependent) diabetes.  
     
     
         60 . The method of  claim 58 , wherein the neuropathy is selected from the group consisting of peripheral neuropathy, sensory neuropathy, polyneuropathy and mononeuropathy.  
     
     
         61 . The method of  claim 58 , wherein the neuropathy comprises a symptom selected from the group consisting of reduced nerve conduction velocity, relacitios, resistance to ischemic block, exaggerated pain response to a painful stimulus and thermal response disorder.  
     
     
         62 . The method of  claim 61 , wherein the nerve is a motor nerve or a sensory nerve.  
     
     
         63 . The method of  claim 62 , wherein the motor nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         64 . The method of  claim 62 , wherein the sensory nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         65 . The method of  claim 61 , wherein the thermal response disorder is selected from the group consisting of thermal hypoalgesia, thermal pain sensation and thermal response latency deficit.  
     
     
         66 . The method of  claim 65 , wherein the thermal response latency is restored.  
     
     
         67 . The method of  claim 61 , wherein a symptom of neuropathy is prevented.  
     
     
         68 . The method of  claim 65 , wherein reduced nerve conduction velocity is prevented.  
     
     
         69 . The method of  claim 67 , wherein thermal hypoalgesia is prevented.  
     
     
         70 . The method of  claim 58 , wherein the neuropathic pain is alleviated.  
     
     
         71 . The method of  claim 70 , wherein the neuropathic pain comprises a symptom selected from the group consisting of hyperalgesia, allodynia, spontaneous pain, pain evoked by light touch and a nerve conduction velocity disorder.  
     
     
         72 . The method of  claim 71 , wherein the hyperalgesia is in response to thermal, mechanical or chemical noxious stimuli.  
     
     
         73 . The method of  claim 72 , wherein the hyperalgesia is reversed.  
     
     
         74 . The method of  claim 71 , wherein the nerve is a sensory nerve.  
     
     
         75 . The method of  claim 71 , wherein the nerve conduction velocity disorder is a decline in sensory nerve conduction velocity.  
     
     
         76 . The method of  claim 71 , wherein the decline in sensory nerve conduction velocity is prevented.  
     
     
         77 . The method of  claim 71 , wherein the progression of an established sensory nerve conduction velocity disorder is halted.  
     
     
         78 . The method of  claim 57 , wherein the administering is selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous, intracranial, epidural, intracerebrospinal, topical, oral, transdermal, transmucosal and transnasal.  
     
     
         79 . The method of  claim 57 , wherein the administering is from the onset of diabetes.  
     
     
         80 . The method of  claim 57 , wherein the administering is after the complications of diabetes are established.  
     
     
         81 . The method of  claim 57 , wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         82 . A method of treating diabetic nerve dysfunction comprising administering to a subject diagnosed with diabetes mellitus an effective amount of a composition, wherein the composition comprises a peptide comprising the sequence shown in SEQ ID NO: 2.  
     
     
         83 . The method of  claim 82 , wherein the diabetes mellitus is type I (insulin dependent) diabetes.  
     
     
         84 . The method of  claim 82 , wherein the diabetic nerve dysfunction is a complication selected from the group consisting of neuropathy and neuropathic pain.  
     
     
         85 . The method of  claim 82 , wherein the diabetic nerve dysfunction comprises a symptom selected from the group consisting of reduced nerve conduction velocity, relacitios, resistance to ischemic block, exaggerated pain response to a painful stimulus, spontaneous pain, pain evoked by light touch, thermal response disorder, allodynia and hyperalgesia.  
     
     
         86 . The method of  claim 84 , wherein the neuropathy is selected from the group consisting of peripheral neuropathy, sensory neuropathy, polyneuropathy and mononeuropathy.  
     
     
         87 . The method of  claim 85 , wherein the nerve is a motor nerve or a sensory nerve.  
     
     
         88 . The method of  claim 87 , wherein the motor nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         89 . The method of  claim 87 , wherein the sensory nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         90 . The method of  claim 85 , wherein the thermal response disorder is selected from the group consisting of thermal hypoalgesia, thermal pain sensation and thermal response latency deficit.  
     
     
         91 . The method of  claim 90 , wherein the thermal response latency is restored.  
     
     
         92 . The method of  claim 85 , wherein a symptom of neuropathy is prevented.  
     
     
         93 . The method of  claim 92 , wherein reduced nerve conduction velocity is prevented.  
     
     
         94 . The method of  claim 90 , wherein thermal hypoalgesia is prevented.  
     
     
         95 . The method of  claim 85 , wherein the hyperalgesia is in response to thermal, mechanical or chemical noxious stimuli.  
     
     
         96 . The method of  claim 85 , wherein the hyperalgesia is reversed.  
     
     
         97 . The method of  claim 89 , wherein the progression of an established sensory nerve conduction velocity disorder is halted.  
     
     
         98 . The method of  claim 82 , wherein the administering is selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous, intracranial, epidural, intracerebrospinal, topical, oral, transdermal, transmucosal and transnasal.  
     
     
         99 . The method of  claim 82 , wherein the administering is from the onset of diabetes.  
     
     
         100 . The method of  claim 82 , wherein the administering is after the complications of diabetes are established.  
     
     
         101 . The method of  claim 82 , wherein the composition further comprises a pharmaceutically acceptable carrier.  
     
     
         102 . A method of treating diabetic nerve dysfunction comprising administering to a subject diagnosed with diabetes mellitus an effective amount of a composition, wherein the composition comprises a peptide consisting of the sequence shown in SEQ ID NO: 2.  
     
     
         103 . The method of  claim 102 , wherein the diabetes mellitus is type I (insulin dependent) diabetes.  
     
     
         104 . The method of  claim 102 , wherein the diabetic nerve dysfunction is a complication selected from the group consisting of neuropathy and neuropathic pain.  
     
     
         105 . The method of  claim 102 , wherein the diabetic nerve dysfunction comprises a symptom selected from the group consisting of reduced nerve conduction velocity, relacitios, resistance to ischemic block, exaggerated pain response to a painful stimulus, spontaneous pain, pain evoked by light touch, thermal response disorder, allodynia and hyperalgesia.  
     
     
         106 . The method of  claim 104 , wherein the neuropathy is selected from the group consisting of peripheral neuropathy, sensory neuropathy, polyneuropathy and mononeuropathy.  
     
     
         107 . The method of  claim 105 , wherein the nerve is a motor nerve or a sensory nerve.  
     
     
         108 . The method of  claim 107 , wherein the motor nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         109 . The method of  claim 107 , wherein the sensory nerve conduction velocity is enhanced or the reduction thereof is slowed.  
     
     
         110 . The method of  claim 105 , wherein the thermal response disorder is selected from the group consisting of thermal hypoalgesia, thermal pain sensation and thermal response latency deficit.  
     
     
         111 . The method of  claim 110 , wherein the thermal response latency is restored.  
     
     
         112 . The method of  claim 105 , wherein a symptom of diabetic nerve dysfunction is prevented.  
     
     
         113 . The method of  claim 112 , wherein reduced nerve conduction velocity is prevented.  
     
     
         114 . The method of  claim 110 , wherein thermal hypoalgesia is prevented.  
     
     
         115 . The method of  claim 105 , wherein the hyperalgesia is in response to thermal, mechanical or chemical noxious stimuli.  
     
     
         116 . The method of  claim 105 , wherein the hyperalgesia is reversed.  
     
     
         117 . The method of  claim 107 , wherein the progression of an established sensory nerve conduction velocity disorder is halted.  
     
     
         118 . The method of  claim 102 , wherein the administering is selected from the group consisting of intravenous, intramuscular, intradermal, subcutaneous, intracranial, epidural, intracerebrospinal, topical, oral, transdermal, transmucosal and transnasal.  
     
     
         119 . The method of  claim 102 , wherein the administering is from the onset of diabetes.  
     
     
         120 . The method of  claim 102 , wherein the administering is after the complications of diabetes are established.  
     
     
         121 . The method of  claim 102 , wherein the composition further comprises a pharmaceutically acceptable carrier.