Neurogenesis by modulating angiotensin

Abstract

The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The invention includes compositions and methods based on modulating angiotensin activity to stimulate or activate the formation of new nerve cells.

1 . A method of treating a nervous system disorder related to cellular degeneration, a psychiatric condition, cellular trauma and/or injury, or another neurologically related condition in a subject or patient, said method comprising administering a modulator of angiotensin activity in combination with one or more neurogenic agents to produce an improvement in said disorder in said subject or patient. 
     
     
         2 . The method of  claim 1 , wherein said nervous system disorder related to cellular degeneration is a neurodegenerative disorder, a neural stem cell disorder, a neural progenitor cell disorder, a degenerative disease of the retina, an ischemic disorder, or a combination thereof. 
     
     
         3 . The method of  claim 1 , wherein said nervous system disorder related to a psychiatric condition is a neuropsychiatric disorder, an affective disorder, depression, hypomania, panic attack, anxiety, excessive elation, bipolar depression, bipolar disorder (manic-depression), seasonal mood (or affective) disorder, schizophrenia and other psychosis, lissencephaly syndrome, anxiety syndrome, anxiety disorder, phobia, stress and related syndrome, cognitive function disorder, aggression, drug and alcohol abuse, obsessive compulsive behavior syndrome, borderline personality disorder, non-senile dementia, post-pain depression, post-partum depression, cerebral palsy, post-traumatic stress disorder (PTSD), or a combination thereof. 
     
     
         4 . The method of  claim 1 , wherein said nervous system disorder related to cellular trauma and/or injury is a neurological trauma and/or injury, surgery related trauma and/or injury, retinal injury and trauma, injury related to epilepsy, spinal cord injury, brain injury, brain surgery, trauma related brain injury, trauma related to spinal cord injury, brain injury related to cancer treatment, spinal cord injury related to cancer treatment, brain injury related to infection, brain injury related to inflammation, spinal cord injury related to infection, spinal cord injury related to inflammation, brain injury related to environmental toxin, spinal cord injury related to environmental toxin, or a combination thereof. 
     
     
         5 . The method of  claim 1 , wherein said neurologically related condition is a learning disorder, memory disorder, autism, attention deficit disorder, narcolepsy, sleep disorder, cognitive disorder, epilepsy, temporal lobe epilepsy, or a combination thereof. 
     
     
         6 . The method of  claim 3 , wherein said psychiatric condition comprises depression. 
     
     
         7 . The method of  claim 1 , wherein said modulator of angiotensin activity is a renin inhibitor, an angiotensin converting enzyme (ACE) inhibitor, or an angiotensin receptor antagonist, or combinations thereof. 
     
     
         8 . The method of  claim 6 , wherein said depression is due to morphine, alcohol, or drug use by the subject or patient. 
     
     
         9 . The method of  claim 7 , wherein said renin inhibitor is aliskerin; said angiotensin converting enzyme inhibitor is alacepril, captopril, enalapril, enalaprilat, ramipril, quinapril, perindopril, lisinopril, fosinopril, benazepril, imidapril, moexipril, or trandolapril; and said angiotensin receptor antagonist is candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan or valsartan. 
     
     
         10 . The method of  claim 1 , wherein said one or more neurogenic agents is a muscarinic agent, an acetylcholinesterase inhibitor, a PDE inhibitor, or a GABA inhibitor. 
     
     
         11 . The method of  claim 10 , wherein said muscarinic agent is alvameline, cevimeline, milameline, sabcomeline or xanomeline; said acetylcholinesterase inhibitor is donepezil, galantamine, (−)-huperzine A, itopride, physostigmine, phenserine, rivastigimine or tacrine; said PDE inhibitor is a non-selective PDE inhibitor, a PDE 3 inhibitor, a PDE 4 inhibitor or a PDE 5 inhibitor; and said GABA agent is baclofen. 
     
     
         12 . The method of  claim 1 , wherein said combination is in a pharmaceutically acceptable formulation. 
     
     
         13 . A method of stimulating or increasing neurogenesis in a cell or tissue, said method comprising contacting said cell or tissue with a modulator of angiotensin activity, and an amount of a neurogenic agent, wherein the combination of the modulator and neurogenic agent is effective to produce neurogenesis in said cell or tissue. 
     
     
         14 . The method of  claim 13 , wherein said modulator of angiotensin activity is a renin inhibitor, an angiotensin converting enzyme (ACE) inhibitor, or an angiotensin receptorantagonist, or combinations thereof. 
     
     
         15 . The method of  claim 14 , wherein said renin inhibitor is aliskerin; said angiotensin converting enzyme inhibitor is alacepril, captopril, enalapril, enalaprilat, ramipril, quinapril, perindopril, lisinopril, fosinopril, benazepril, imidapril, moexipril, or trandolapril; and said angiotensin receptor antagonist is candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan or valsartan. 
     
     
         16 . The method of  claim 13 , wherein said one or more neurogenic agents is a muscarinic agent, an acetylcholinesterase inhibitor, a PDE inhibitor, or a GABA inhibitor. 
     
     
         17 . The method of  claim 16 , wherein said muscarinic agent is alvameline, cevimeline, milameline, sabcomeline or xanomeline; said acetylcholinesterase inhibitor is donepezil, galantamine, (−)-huperzine A, itopride, physostigmine, phenserine, rivastigimine or tacrine; said PDE inhibitor is a non-selective PDE inhibitor, a PDE 3 inhibitor, a PDE 4 inhibitor or a PDE 5 inhibitor; and said GABA agent is baclofen. 
     
     
         18 . The method of  claim 13 , wherein said cell or tissue is in an animal subject or a human patient. 
     
     
         19 . The method of  claim 18 , wherein said patient is in need of neurogenesis or has been diagnosed with a disease, condition, or injury of the central or peripheral nervous system. 
     
     
         20 . The method of  claim 13 , wherein said cell or tissue exhibits decreased neurogenesis or is subjected to an agent which decreases or inhibits neurogenesis.