Provided are methods of treating a lysosomal storage disorder in a mammal which method includes administering AAV particles encoding a polypeptide to the central nervous system of the mammal. AAV particles may be delivered by direct injection into the brain, spinal cord, cerebral spinal fluid or a portion thereof for expression.

This disclosure provides a method of reducing neuroinflammation or correcting brain weight loss in a subject. The method comprises administering to the subject a therapeutically effective amount of an agent that increases a level or activity of TPP1.

Formulations comprising recombinant human tripeptidyl peptidase-1 (rhTPP1) for intrathecal, intracerebroventricular, or intraocular administration, and kits comprising the same, are disclosed. Methods of using rhTPP1 in the prevention and treatment of symptoms of Neuronal Ceroid Lipofuscinosis (CLN2) disease are also disclosed. The formulations and methods are effective in halting the progression of CLN2 disease and may be used to treat subjects having CLN2 or a family history of CLN2.

Methods and uses of treating a disease in a mammal are provided by administering to a mammalian non-central nervous system (CNS) cell, organ or tissue, for delivery to mammalian CNS (e.g., brain). Methods and uses of treating a disease in a mammal include, inter alia, administering to a mammalian non-ocular cell, organ or tissue for delivery to a mammalian ocular cell, organ or tissue.

Provided herein are methods of selective screening. In addition, various targeting proteins and sequences, as well as methods of their use, are also provided.

Provided herein are methods of selective screening. In addition, various targeting proteins and sequences, as well as methods of their use, are also provided.

Formulations comprising recombinant human tripeptidyl peptidase-1 (rhTPP1) for intrathecal, intracerebroventricular, or intraocular administration, and kits comprising the same, are disclosed. Methods of using rhTPP1 in the prevention and treatment of symptoms of Neuronal Ceroid Lipofuscinosis (CLN2) disease are also disclosed. The formulations and methods are effective in halting the progression of CLN2 disease and may be used to treat subjects having CLN2 or a family history of CLN2.

Provided herein are methods of selective screening. In addition, various targeting proteins and sequences, as well as methods of their use, are also provided.

A method of preparing a feed additive composition comprising: (a) admixing at least one proline tolerant tripeptidyl peptidase predominantly having exopeptidase activity wherein said proline tolerant tripeptidyl peptidase is capable of cleaving tri-peptides from the N-terminus of peptides having (i) (A) Proline at P1; and (B) An amino acid selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine or synthetic amino acids at P1; or (ii) (a) Proline at P1; and (b) An amino acid selected from alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tryptophan, tyrosine, valine or synthetic amino acids or amines at P1; and one or more ingredients selected from the group consisting of a salt, polyol including sorbitol and glycerol, wheat or a wheat component, sodium acetate, sodium acetate trihydrate, potassium sorbate Talc, polyvinyl alcohol (PVA), benzoate, sorbiate, 1,3-propane diol, glucose, parabens, sodium chloride, citrate, metabisulfite, formate or a combination thereof; and (b) optionally packaging as well as uses of such proline tolerant tripeptidyl peptidases, feed additive compositions, feed additive kits, feeds or feedstuffs and/or premixes.

The present disclosure provides methods of treating a lysosomal storage disorder in a mammal which method comprises administering AAV particles encoding a polypeptide directly to the central nervous system of the mammal in conjunction with administering at least two immunosuppressive agents. AAV particles may be delivered by direct injection into the brain, spinal cord, cerebral spinal fluid or a portion thereof.