Abstract: The invention relates to neurodegenerative disorders, and in particular to novel oligonucleotides for treating such conditions, for example Alzheimer's disease. The invention provides novel antisense oligonucleotides, and compositions comprising such oligos, and therapies and methods for treating neurodegenerative disorders. The invention includes genome editing techniques for achieving similar results as using the novel antisense oligonucleotides.

Abstract: Compositions for the treatment of shock, autodigestion, multi-organ failure, intestinal ischemia, or intestinal hypoperfusion are provided.

Abstract: Methods and compositions for identifying autoimmune diabetes are provided. One aspect provides a method for the evaluation of risk and progression of autoimmune diabetes in mammalian subjects. The method includes measuring the enzymatic activities and/or protein concentrations of neutrophil elastase and proteinase 3 in a subject and comparing the measured levels of these proteases to respective reference levels.

Abstract: Compositions for the treatment of shock, autodigestion, multi-organ failure, intestinal ischemia, or intestinal hypoperfusion are provided.

Abstract: The present invention provides boronic acid compounds, boronic esters, and compositions thereof that can modulate apoptosis such as by inhibition of proteasome activity. The compounds and compositions can be used in methods of inducing apoptosis and treating diseases such as cancer and other disorders associated directly of indirectly with proteasome activity.

Abstract: Pharmacological chaperone compounds and methods for the treatment of an individual having, or at risk of having, a disease condition associated with alpha-1-antitrypsin by using said compounds are disclosed. In particular, such methods are useful for the treatment or prevention of lung disorders associated with alpha-1-antitrypsin deficiency as well as liver disorders associated with an excess of alpha-1-antitrypsin. Suitable pharmacological chaperones include peptides and low-molecular weight compounds. Also provided is an assay for determining whether a test compound modulates alpha-1-antitrypsin activity.

Abstract: The present invention refers to a vector for gene therapy comprising a TFEB coding sequence under the control of a promoter able to efficiently express said TFEB coding sequence, to host cell comprising said vector and to their use in the gene therapy of a pathological condition characterized by a deficiency of alpha-1-antitrypsin (AAT). The present invention also refers to a pharmaceutical composition comprising the vector or the host cell of the invention for gene therapy and to a method for gene therapy of a pathological condition characterized by a deficiency of alpha-1-antitrypsin (AAT).

Abstract: Elastic fiber damage is responsible for the distention and rupture of alveolar walls in chronic obstructive pulmonary disease (COPD). The current invention comprises a method of adjusting the a dosage of a drug that prevents such elastic fiber damage by employing a feedback loop consisting of measuring the levels of the unique elastic fiber breakdown products, desmosine and isodesmosine in body fluids, preferably sputum. The recent discovery that sputum levels of desmosine and isodesmosine are responsive to treatment with aerosolized hyaluronan in COPD patients makes dosage adjustment both feasible and desirable. This process of dosage adjustment may be applicable to any drug that prevents lung elastic fiber damage, such as alpha-1-antitrypsin, other anti-elastase agents, and antioxidants. It is anticipated that such dosage adjustment will become the “standard of care” in the treatment of COPD patients.

Abstract: A method of preparing an oxidised polysaccharide-protein conjugate by oxidising a polysaccharide with an oxidising agent to form an oxidised polysaccharide and combining such oxidised polysaccharide with a protein. The oxidised polysaccharide is reacted with a protein to form a composition comprising a conjugate wherein the oxidised polysaccharide and the protein are conjugated via one or more imine bonds and wherein the oxidised polysaccharide comprises essentially no alpha-hydroxy aldehyde units. The conjugate may be used to provide sustained or latent activity of the protein.

Abstract: The invention is directed to the use of peptides that can bind and block the interaction of ?1 proteinase inhibitor (?1PI) and one or more molecules, for example antibodies to HIV-1 envelope proteins. The invention features methods of activating ?1PI in a cell, methods of treating or preventing a disease or disorder in a subject, for example HIV-1 or AIDS. The invention also features pharmaceutical compositions comprising one or more peptides that block the interaction of ?1 ?1PI and one or more molecules. Also included in the invention are kits.

Abstract: A novel alpha-1 antitrypsin variant, a method of preparing the same, and use thereof are provided. The alpha-1 antitrypsin variant has excellent stability in the body and maintains an inhibitory effect on elastase activities because the blood half-life (t1/2) and the area under blood drug concentration vs. time curve (AUC) are remarkably increased by adding an N-glycosylation site in animal cells through amino acid mutation between 1st and 25th positions of the N-terminus of alpha-1 antitrypsin. Therefore, the alpha-1 antitrypsin variant can be useful in preventing or treating alpha-1 antitrypsin deficiency.

Abstract: Template-fixed ?-hairpin peptidomimetics of the general formulae wherein Z is a chain of 11 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or Pro(4NHCOPhe), or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have the property to inhibit proteases, in particular serine proteases, especially Cathepsin G or Elastase or Tryptase. These ?-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

Abstract: The present invention relates to methods and compositions for sealing localized regions of damaged lung tissue to reduce overall lung volume. The glue compositions provide a glue featuring an adhering moiety coupled to one or more other moieties including, for example, a cross-linkable moiety and/or one other adhering moiety. The methods and compositions of the invention find use, for example, in treating pulmonary conditions, such as emphysema.

Abstract: The inventors have unexpectedly discovered that shock and/or potential multi-organ failure due to shock can be effectively treated by administration of liquid high-dose protease inhibitor formulations to a location upstream of where pancreatic proteases are introduced into the gastrointestinal tract. Most preferably, administration is directly to the stomach, for example, via nasogastric tube under a protocol effective to treat shock by such administration without the need of providing significant quantities of the protease inhibitor to the jejunum and/or ileum.

Abstract: Pharmacological chaperone compounds and methods for the treatment of an individual having, or at risk of having, a disease condition associated with alpha-1-antitrypsin by using said compounds are disclosed. In particular, such methods are useful for the treatment or prevention of lung disorders associated with alpha-1-antitrypsin deficiency as well as liver disorders associated with an excess of alpha-1-antitrypsin. Suitable pharmacological chaperones include peptides and low-molecular weight compounds. Also provided is an assay for determining whether a test compound modulates alpha-1-antitrypsin activity.

Abstract: An elastase inhibitor that contains as active ingredients thereof raspberry extract and hydroxyproline, and optionally further contains yeast extract.

Abstract: A method of treating a patient suffering from a disease characterized by tissue necrosis by administering to the patient a necrosis inhibitor and/or a Humanin or a derivative of Humanin is provided. The invention further includes a method for prophylactically treating a patient at risk for a pathological condition that is precipitated at least in part by tissue necrosis by administering to the patient a necrosis inhibitor and/or a Humanin or a derivative of Humanin.

Abstract: The present invention relates to methods and compositions for sealing localized regions of damaged lung tissue to reduce overall lung volume. The glue compositions provide a glue featuring an adhering moiety coupled to one or more other moieties including, for example, a cross-linkable moiety and/or one other adhering moiety. The methods and compositions of the invention find use, for example, in treating pulmonary conditions, such as emphysema.

Abstract: The present invention relates recombinant human ?1-antitrypsin (rhAAT) comprising N-linked glycans, wherein at least 10% of said N-linked glycans are tetra-antennary glycans; and the degree of capping with sialic acid on said N-linked glycans (Z/A) is at least 50%. The invention further relates to rhAAT for use as a medicament, in particular for use in the prevention and/or treatment of a disease associated with AAT deficiency, and/or a disease involving neutrophil-mediated tissue damage.

Abstract: A method for treating and/or preventing cell necrosis and diseases associated therewith, comprising the inhibition of one or more elastase enzymes within said cells.

Abstract: A previously unrecognized fundamental property of ?1PI is to regulate the phenotypic composition of circulating and tissue-associated cells derived from hematopoietic stem cells. The present invention comprises screening for various unmodified and modified ?1PI's which are useful in the treatment of abnormalities in the number of cells of myeloid or lymphoid lineage that are associated with HW-1 infection, microbial infection, leukemia, solid tumor cancers, atherosclerosis, autoimmunity, stem cell transplantation, organ transplantation, and other diseases affected by cells of the immune system. The interaction of ?1PI with its receptors, HLECS and LRP, influences the level of cells of different lineages. Genetic and proteolytic modification of ?1PI is used to target these receptors to increase or decrease specific cell populations, as needed, in the various disease states.

Abstract: The present invention relates to methods and compositions for sealing localized regions of damaged lung tissue to reduce overall lung volume. The glue compositions provide a glue featuring an adhering moiety coupled to one or more other moieties including, for example, a cross-linkable moiety and/or one other adhering moiety. The methods and compositions of the invention find use, for example, in treating pulmonary conditions, such as emphysema.

Abstract: The present invention relates to the use of alpha-1-antitrypsin for the preparation of effective drugs for the treatment of chronic fatigue syndrome. In addition, the present invention relates to the use of plasma or other therapeutic forms with an alpha-1-antitrypsin content sufficient to obtain a dose of 6 mg or more of alpha-1-antitrypsin per kg of body weight at a frequency of between 1 and 31 days.

Abstract: This invention relates to novel glucocorticoid receptor agonists of formula (I): and to processes and intermediates for their preparation. The present invention also relates to pharmaceutical compositions containing these compounds, to their combination with one or more other therapeutic agents, as well as to their use for the treatment of a number of inflammatory and allergic diseases, disorders and conditions.