Neurotherapeutic Nanoparticle Compositions and Devices

Abstract

There are provided compositions and methods for treatment of neurodegeneative diseases and CNS injury. The compositions a pharmaceutically acceptable carrier solution; and a plurality of biodegradable nanoparticles, wherein the nanoparticles comprise a targeting moiety that is able to bind selectively to the surface of a neural stem cell and wherein the nanoparticles further comprise factors such as leukaemia inhibitory factor (LIF); XAV939 and/or one or more of : brain-derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. The biodegradable nanoparticles may deliver via controlled time release.

What is claimed is: 
     
         1 . A composition for the treatment of neurodegenerative disease comprising:
 a) a pharmaceutically acceptable carrier solution; and   b) a plurality of biodegradable nanoparticles,
 the nanoparticles being comprised of a biodegradable polymer matrix that encapsulates a cargo, 
 the nanoparticles further comprising a targeting moiety located on the surface of the nanoparticle, the targeting moiety selected from a monoclonal antibody and an antigen-binding fragment thereof, the targeting moiety being able to bind selectively to an antigen on the surface of a neural cell selected from the group consisting of: a neural stem cell; a neural progenitor cell; a precursor cell that is commited to a neurectodermal lineage; and a neuronal cell; and wherein 
 the cargo comprises leukaemia inhibitory factor (LIF). 
   
     
     
         2 . The composition of  claim 1 , wherein the polymer comprises poly(lactic)-co-glycolic acid (PLGA) and/or PLA. 
     
     
         3 . The composition of  claim 1 , wherein the targeting moiety binds specifically to a Thy-1 antigen present on the surface of the neural stem cell. 
     
     
         4 . The composition of  claim 1 , wherein the targeting moiety binds specifically to a NCAM antigen present on the surface of the neural stem cell. 
     
     
         5 . The composition of  claim 1 , wherein the targeting moiety binds specifically to a glial cell line derived neurotrophic factor receptor α1(GDNFR-α1) present on the surface of the neural stem cell. 
     
     
         6 . The composition of  claim 1 , wherein the nanoparticles further comprise one or more of the following therapeutic compounds: brain-derived neurotrophic factor (BDNF) or an agonist thereof; epidermal growth factor (EGF) or an agonist thereof; glial cell-derived neurotrophic factor (GDNF) or an agonist thereof; retinoic acid and derivatives thereof; ciliary neurotrophic factor (CTNF) or an agonist thereof; and Wnt5A. 
     
     
         7 . The composition of  claim 1 , wherein the nanoparticles have a diameter of at least about 50 nm and at most about 300 nm. 
     
     
         8 . The composition of  claim 1 , wherein the nanoparticles are capable of degrading of a period of time in order to effect timed release of the encapsulated LIF. 
     
     
         9 . The composition of  claim 8 , wherein the period of time is selected from the group consisting of: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 days; 1, 2, 3, 4, 5 or 6 weeks; and up to six months. 
     
     
         10 . A method for treating a patient suffering from a neurodegenerative disease (NDD) or CNS damage comprising administering to the subject a pharmaceutical composition of  claim 1 . 
     
     
         11 . A nanoparticle for use in the treatment of neurodegenerative disease and/or CNS damage comprising:
 a biodegradable carrier material, a therapeutic compound, and a targeting moiety;   wherein the carrier material is configured so to encapsulate the therapeutic compound and wherein the carrier material further defines a surface, upon and within which surface is located the targeting moiety,   the nanoparticle further characterised in that the therapeutic compound comprises LIF and the surface located targeting moiety comprises an antibody, or an antigen binding fragment of an antibody, that specifically binds to an antigen present on the cell surface of a stem cell having the capacity to act as a neural precursor cell.   
     
     
         12 . The nanoparticle of  claim 11 , wherein the biodegradable carrier material degrades at a rate that allows for controlled release of the LIF over a pre-determined period of time. 
     
     
         13 . The nanoparticle of  claim 11 , wherein the targeting moiety binds specifically to a Thy-1 antigen present on the surface of the stem cell. 
     
     
         14 . The nanoparticle of  claim 11 , wherein the targeting moiety binds specifically to a NCAM antigen present on the surface of the cell. 
     
     
         15 . The nanoparticle of  claim 11 , wherein the targeting moiety binds specifically to a GDNFR-α1 present on the surface of the cell. 
     
     
         16 . The nanoparticle of  claim 11 , wherein the nanoparticle has a diameter of at least about 50 nm and at most about 300 nm. 
     
     
         17 . The nanoparticle of  claim 16 , wherein the nanoparticle has a diameter of at least about 100 nm and at most about 200 nm. 
     
     
         18 . The nanoparticle of  claim 11 , wherein the neurodegenerative disease is selected from the group consisting of: Alzheimer's Disease (AD), Multiple Sclerosis (MS); Parkinson's Disease (PD); Huntington's Disease (HD); Frontotemporal dementia (FTD); and Amyotrophic Lateral Sclerosis (ALS).