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: A pharmaceutical composition includes a ferrochelatase inhibitor and a pharmaceutically acceptable carrier. In another aspect, a method of treating a subject having, or at risk of having, a hemorrhagic stroke generally includes administering to the subject a pharmaceutical composition that includes a ferrochelatase inhibitor in an amount effective to ameliorate at least one symptom or clinical sign of hemorrhagic stroke.

Abstract: A pharmaceutical composition includes a ferrochelatase inhibitor and a pharmaceutically acceptable carrier. In another aspect, a method of treating a subject having, or at risk of having, a hemorrhagic stroke generally includes administering to the subject a pharmaceutical composition that includes a ferrochelatase inhibitor in an amount effective to ameliorate at least one symptom or clinical sign of hemorrhagic stroke.

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: A pharmaceutical composition includes a ferrochelatase inhibitor and a pharmaceutically acceptable carrier. In another aspect, a method of treating a subject having, or a t risk of having, a hemorrhagic stroke generally includes administering to the subject a pharmaceutical composition that includes a ferrochelatase inhibitor in an amount effective to ameliorate at least one symptom or clinical sign of hemorrhagic stroke.

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: 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: Methods and apparatus for determining blood brain barrier (BBB) damage and treating patients who may have suffered from BBB damage due to an ischemic event are provided. The methods and apparatus involve detecting the presence of cleaved occludin fragments in a sample of blood. According to some embodiments, the method further provides determining the degree of BBB damage based on the concentration of occludin fragments in the sample. In further embodiments the present disclosure provides kits for detecting the presence of occludin fragments in a blood sample.

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 the discovery that pyrazinamide, a potent anti-tuberculosis agent acts through an entirely unexpected mechanism-through inhibition of the host enzyme poly ADP ribose polymerase (“PARP”). Thus, the present invention is directed to methods of treating: mycobacterial infections (Mycobacterium), especially M. tuberculosis using a PARP inhibitor, optionally in combination with at least one additional agent useful in the treatment of a mycobacterial infection, especially tuberculosis. Pharmaceutical compositions, especially including a pharmaceutical composition in oral or inhalation dosage form, comprising a inhibitor, optionally in combination with an additional anti-mycobacterial agent, especially an additional anti-tuberculosis agent represent additional embodiments of the present invention.

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: Methods and apparatus for determining blood brain barrier (BBB) damage and treating patients who may have suffered from BBB damage due to an ischemic event are provided. The methods and apparatus involve detecting the presence of cleaved occludin fragments in a sample of blood. According to some embodiments, the method further provides determining the degree of BBB damage based on the concentration of occludin fragments in the sample. In further embodiments the present disclosure provides kits for detecting the presence of occludin fragments in a blood sample.

Abstract: In one embodiment, the invention provides a method of treating a subject who suffers from, or who is suspected of suffering from, a Mycobacterium infection, the method comprising administering to the subject a therapeutically effective amount of a urease inhibitor, optionally in combination with one or more anti-mycobacterial agents.

Abstract: This disclosure describes compositions, vaccine, and methods that involve a biocomposite material Generally, the biocomposite material includes a cell and a lipid-silica matrix at least partially encapsulating the cell. In some cases, the cell can be viable but not culturable (VBNC). In some cases, the lipid-silica matrix includes a dried sol and/or possesses ordered nanostructure.

Abstract: The present invention is directed to methods of determining the presence or absence of a bacterial infection in a patient using isotopically-labeled tyrosine and/or isotopically-labeled p-hydroxyphenylacetic acid.

Abstract: Methods and apparatus for determining blood brain barrier (BBB)damage and treating patients who may have suffered from BBB damage due to an ischemic event are provided. The methods and apparatus involve detecting the presence of cleaved occludin fragments in a sample of blood. According to some embodiments, the method further provides determining the degree of BBB damage based on the concentration of occludin fragments in the sample. In further embodiments the present disclosure provides kits for detecting the presence of occludin fragments in a blood sample.

Abstract: Methods and apparatus for determining blood brain barrier (BBB) damage and treating patients who may have suffered from BBB damage due to an ischemic event are provided. The methods and apparatus involve detecting the presence of cleaved occludin fragments in a sample of blood. According to some embodiments, the method further provides determining the degree of BBB damage based on the concentration of occludin fragments in the sample. In further embodiments the present disclosure provides kits for detecting the presence of occludin fragments in a blood sample.

Abstract: Methods and apparatus for determining blood brain barrier (BBB) damage and treating patients who may have suffered from BBB damage due to an ischemic event are provided. The methods and apparatus involve detecting the presence of cleaved occludin fragments in a sample of blood. According to some embodiments, the method further provides determining the degree of BBB damage based on the concentration of occludin fragments in the sample. In further embodiments the present disclosure provides kits for detecting the presence of occludin fragments in a blood sample.

Abstract: In one embodiment, the invention provides a method of treating a subject who suffers from, or who is suspected of suffering from, a Mycobacterium infection, the method comprising administering to the subject a therapeutically effective amount of a urease inhibitor, optionally in combination with one or more anti-mycobacterial agents.

Abstract: The invention provides method of treating a subject suffering from, or at risk of developing, a Mycobacterium infection by administering to the subject a therapeutically-effective amount of isotopically labeled isoniazid and/or ethionamide, or an analog, derivative or prodrug thereof, and exposing the subject to a magnetic field.