Abstract: The present invention relates to discovery that TBK1 phosphorylates Syntaxin 17 and that phosphorylation of Syntaxin 17 is intimate to control autophagy initiation. The present invention is directed to this discovery and the use of TBK1 inhibitors or inhibitors of Syntaxin 17 phosphorylation alone or in combination with additional bioactive agents to inhibit autophagy in the treatment of disease, especially the treatment of cancers. Methods of treating various cancers are disclosed using TBK1 inhibitors to patients with cancer and into cancerous tissues for the treatment of cancer including the inhibition, amelioration, reduction in metastasis and in recurrence of cancer in remission. Assays and methods for identifying compounds as inhibitors of Syntaxin 17 and as potential therapeutic agents for cancer and autoimmune diseases are also diseased herein.

Abstract: The present invention is directed to the discovery that AMPK activation through Galectin 9 induces autophagy and affects other related processes in response to lyosomal damage which occurs and the use of that mechanism in the treatment of autophagy disease states and/or conditions. The use of modulators of AMPK and optionally a modulator of Galectin 9, TAK1 and/or a lysosomotropic agent for the treatment of autophagy-mediated disease states and/or conditions is described as are pharmaceutical compositions.

Abstract: The present invention is directed to elucidating the mechanism of formation of autophagosomal membranes that emerge via convergence of secretory and endosomal pathways and providing therapeutic approaches to the treatment of several acute respiratory syndrome coronavirus 1 (SARS) and 2 SARS-CoV-2), MERS-CoV and numerous other autophagy-mediated diseases based upon this mechanism. This process is targeted by microbial factors such as coronaviral membrane modulating proteins and represents a potential target for agents which may be used in the treatment of SARS, COVID and MERS. The present invention is also directed to compositions and methods for the treatment of SARS, COVID and/or MERS and other autophagy-mediated disease states.

Abstract: The present invention is directed to 13C and/or 2H isotope enhanced ambroxol (“isotope enhanced ambroxol”) and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drug resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced ambroxol, alone or in combination with an additional bioactive agent are useful against an autophagy mediated disease state and/or condition, for example, a Mycobacterium infection, Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention.

Abstract: The present invention is directed to the discovery that Galectin-3 (Gal3) governs and coordinates ESCRT and autophagic responses in subjects and that compositions and methods of treatment can make use of this discovery in the treatment of autophagy mediated disease states and/or conditions.

Abstract: The present invention is directed to the discovery that AMPK activation through Galectin 9 induces autophagy and affects other related processes in response to lyosomal damage which occurs and the use of that mechanism in the treatment of autophagy disease states and/or conditions. The use of modulators of AMPK and optionally a modulator of Galectin 9, TAK1 and/or a lysosomotropic agent for the treatment of autophagy-mediated disease states and/or conditions is described as are pharmaceutical compositions.

Abstract: The present invention is directed to the discovery that Galectins and in particular, Galectin-8 and Galectin-9 control mTor response (Galectin-8 is a mTOR inhibitor and Galectin-9 is modulator/upregulator of AMPKinase) to endomembrane damage and these compositions can be used, either alone or together, optionally in combination with a lysomotropic agent and other bioactive agents as compositions for the treatment of autophagy-elated diseases. The present invention is directed to pharmaceutical compositions and methods for treating autophagy-related diseases as described herein.

Abstract: The present invention is directed to the elucidation of the mechanism that human Atg8 protein regulates endolysosomal systems in the cell and the role this protein plays in mediating autophagy. Methods of treating autophagy-mediated disease states with agonists/antagonists of Atg8, STX16 and STX17 proteins are disclosed as are pharmaceutical compositions.

Abstract: In one embodiment, the invention provides a method of treating a subject suffering from a Mycobacterium infection by administering to the subject a therapeutically-effective amount of a degradative autophagy agonist or a secretory autophagy antagonist. In another embodiment, the invention provides a method of treating a subject suffering from one or more diseases selected from the group consisting of a Mycobacterium infection, an inflammatory disorder, an immune disorder, a cancer and a neurodegenerative disorder by administering to the subject a therapeutically-effective amount of a TBK-1 antagonist (e.g. BX795 or amlexanox). Related pharmaceutical compositions, diagnostic and screening assays and kits are also provided.

Abstract: The present invention is directed to 13C and/or 2H isotope enhanced ambroxol (“isotope enhanced ambroxol”) and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced ambroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection.

Abstract: The present invention relates to the discovery that IRGM, encoded by a uniquely human gene which confers risk for inflammatory diseases, affects autoophagy through a hitherto unknown mechanism. The present invention shows that IRGM controls autophagy and that IRGM modulators, in particular, double-stranded RNA, including poly I:C, poly-UG (polyUGUGU) and polyICLC and muramyldipeptide and related analogs of same, including N-acetyl muramyl-L-alanyl-D-isoglutamine (Muramyl dipeptide or MDP) and numerous other compounds as identified herein, which may be used alone, in combination, or in combination with alternative autophagy modulators and additional bioactive agents to provide effective therapies for a number of diseases, including cancer, bacterial infections and inflammatory diseases, especially including tuberculosis infections and Crohn's disease, among others.

Abstract: The present invention is directed to 2H isotope enhanced ambroxol (“isotope enhanced ambroxol”) and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drug resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced ambroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy) are also disclosed. These compositions are useful against an autophagy mediated disease state and/or condition), especially an autophagy mediated disease state and/or condition which occurs in the lungs.

Abstract: The present invention is directed to 13C and/or 2H isotope enhanced ambroxol (“isotope enhanced ambroxol”) and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced ambroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an autophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection.

Abstract: In one embodiment, the invention provides a method of treating a subject suffering from a Mycobacterium infection by administering to the subject a therapeutically-effective amount of a degradative autophagy agonist or a secretory autophagy antagonist. In another embodiment, the invention provides a method of treating a subject suffering from one or more diseases selected from the group consisting of a Mycobacterium infection, an inflammatory disorder, an immune disorder, a cancer and a neurodegenerative disorder by administering to the subject a therapeutically-effective amount of a TBK-1 antagonist (e.g. BX795 or amlexanox). Related pharmaceutical compositions, diagnostic and screening assays and kits are also provided.

Abstract: The present invention relates to the discovery that IRGM, encoded by a uniquely human gene which confers risk for inflammatory diseases, affects autoophagy through a hitherto unknown mechanism. The present invention shows that IRGM controls autophagy and that IRGM modulators, in particular, double-stranded RNA, including poly I:C, poly-UG (polyUGUGU) and polyl-CLC and muramyldipeptide and related analogs of same, including N-acetyl muramyl-L-alanyl-D-isoglutamine (DMP) and numerous other compounds as identified herein, which may be used alone, in combination, or in combination with alternative autophagy modulators and additional bioactive agents to provide effective therapies for a number of diseases, including cancer, bacterial infections and inflammatory diseases, especially including tuberculosis infections and Crohn's disease, among others.

Abstract: The present invention relates to the use of neutral lipids, including triglycerides, diglycerides and monoglycerides which may be used to increase neutral lipids (lipid stores and/or lipid droplets) and neutral lipid stores in order to regulate (in particular, induce) autophagy and treat and/or prevent autophagy related disease states and/or conditions. In one embodiment, the invention relates to the use of neutral lipids and/or TRIM proteins which may be used to regulate (in particular, induce) autophagy, target autophagic substrates and treat and/or prevent autophagic disease states and/or conditions.

Abstract: The present invention relates to the use of neutral lipids, including triglycerides, diglycerides and monoglycerides which may be used to increase neutral lipids (lipid stores and/or lipid droplets) and neutral lipid stores in order to regulate (in particular, induce) autophagy and treat and/or prevent autophagy related disease states and/or conditions. In one embodiment, the invention relates to the use of neutral lipids and/or TRIM proteins which may be used to regulate (in particular, induce) autophagy, target autophagic substrates and treat and/or prevent autophagic disease states and/or conditions.

Abstract: In one embodiment, the invention provides a method of treating a subject suffering from a Mycobacterium infection by administering to the subject a therapeutically-effective amount of a degradative autophagy agonist or a secretory autophagy antagonist. In another embodiment, the invention provides a method of treating a subject suffering from one or more diseases selected from the group consisting of a Mycobacterium infection, an inflammatory disorder, an immune disorder, a cancer and a neurodegenerative disorder by administering to the subject a therapeutically-effective amount of a TBK-1 antagonist (e.g. BX795 or amlexanox). Related pharmaceutical compositions, diagnostic and screening assays and kits are also provided.

Abstract: The present invention relates to the use of isotopically labeled derivatives of isoniazid, ethionamide and related compounds as effective therapy for the treatment of mycobacterial diseases, including Mycobacterium tuberculosis.

Abstract: The present invention relates to methods for detecting P aeruginosa infection and bacterial burden in the lungs of patients who are at risk for P. aeruginosa infections, especially including patients with Cystic Fibrosis (CF). The present method provides numerous tests (breath, blood, urine) which are readily administered to a patient that will sensitively and specifically detect the presence and extent of lung infection P. aeruginosa (both mucoid and non-mucoid), and allow monitoring of bacterial load as a parameter in monitoring treatment.