It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

It is provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis. It is also provided a catechol-O-methyltransferase (COMT) inhibitor for use in the prevention and/or treatment of transthyretin-associated amyloidosis in combination therapy with another COMT inhibitor, a benzoxazole derivative, iododiflunisal, diflunisal, resveratrol, tauroursodeoxycholic acid, doxocycline, or epigallocatechin-3-gallate.

The disclosure provides biomarkers for diagnosis and monitoring of transthyretin (TTR) amyloidosis. The disclosure further provides methods for selection of agents for treatment of TTR amyloidosis using the biomarkers. The disclosure further provides kits for practicing the methods provided herein.

The disclosure provides biomarkers for diagnosis and monitoring of transthyretin (TTR) amyloidosis. The disclosure further provides methods for selection of agents for treatment of TTR amyloidosis using the biomarkers. The disclosure further provides kits for practicing the methods provided herein.

The present invention relates to the field of therapeutics and, more in particular, to pharmaceutical compositions for the prevention and/or treatment of bacterial infections and antibacterial-induced dysfunctions. The invention is based on the identification of compounds that prevent antibacterial effects of antibiotics on microbiome-bacterial species, while retaining antibacterial effects of antibiotics on pathogenic bacteria. The invention also pertains to pharmaceutical compositions comprising antibiotics and antibiotic antidotes for the protection of commensal microbiome-bacteria. Thus, this invention relates to compounds and pharmaceutical combinations useful to prevent antibiotic-induced adverse effects on the gut microbiome. Furthermore provided are methods for preventing an adverse effect on a gut microbiome using the compounds and/or pharmaceutical compositions of this invention.

The present invention relates to the field of therapeutics and, more in particular, to pharmaceutical compositions for the prevention and/or treatment of bacterial infections and antibacterial-induced dysfunctions. The invention is based on the identification of compounds that prevent antibacterial effects of antibiotics on microbiome-bacterial species, while retaining antibacterial effects of antibiotics on pathogenic bacteria. The invention also pertains to pharmaceutical compositions comprising antibiotics and antibiotic antidotes for the protection of commensal microbiome-bacteria. Thus, this invention relates to compounds and pharmaceutical combinations useful to prevent antibiotic-induced adverse effects on the gut microbiome. Furthermore provided are methods for preventing an adverse effect on a gut microbiome using the compounds and/or pharmaceutical compositions of this invention.

The invention addresses radioresistance in cancer treatment involving radiotherapy and, in particular, limitations associated with the use of the drug sulfasalazine. Specifically, it provides a series of compounds for use as radiosensitizers in the treatment of cancers such as glioblastomas which are lethal and inherently resistant to radiotherapy. In one embodiment, the invention provides compounds of general formula (I), their stereoisomers and pharmaceutically acceptable salts for use as radiosensitizers in the treatment of cancer:

##STR00001##

wherein ring A is selected from optionally substituted phenyl, biphenyl and fluorenyl; each X is independently selected from: —C.sub.1-6 alkyl (preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), —O—C.sub.1-6 alkyl (preferably —O—C.sub.1-3 alkyl, e.g. —OCH.sub.3), —S—C.sub.1-6 alkyl (preferably —S—C.sub.1-3 alkyl, e.g. —SCH.sub.3), —OH, —SH, —CO.sub.2R.sup.1 (where R.sup.1 is H or C.sub.1-6 alkyl, preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), —SO.sub.2—C.sub.1-6 alkyl (preferably —SO.sub.2—C.sub.1-3 alkyl, e.g. —SO.sub.2—CH.sub.3), —SO.sub.2—NR.sup.2R.sup.3 (where R.sup.2 is H and R.sup.3 is optionally substituted phenyl), —NR.sup.4R.sup.5 (wherein R.sup.4 and R.sup.5 are independently selected from H, C.sub.1-6 alkyl (preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), and —CO—C.sub.1-6 alkyl (preferably —CO—C.sub.1-3 alkyl, e.g. —CO—CH.sub.3), halogen (e.g. F, Cl or Br), and optionally substituted tetrazolyl; n is an integer from 0 to 5, preferably 0 to 2, e.g. 1 or 2; and denotes an E or Z double bond.

The invention addresses radioresistance in cancer treatment involving radiotherapy and, in particular, limitations associated with the use of the drug sulfasalazine. Specifically, it provides a series of compounds for use as radiosensitizers in the treatment of cancers such as glioblastomas which are lethal and inherently resistant to radiotherapy. In one embodiment, the invention provides compounds of general formula (I), their stereoisomers and pharmaceutically acceptable salts for use as radiosensitizers in the treatment of cancer:

##STR00001##

wherein ring A is selected from optionally substituted phenyl, biphenyl and fluorenyl; each X is independently selected from: —C.sub.1-6 alkyl (preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), —O—C.sub.1-6 alkyl (preferably —O—C.sub.1-3 alkyl, e.g. —OCH.sub.3), —S—C.sub.1-6 alkyl (preferably —S—C.sub.1-3 alkyl, e.g. —SCH.sub.3), —OH, —SH, —CO.sub.2R.sup.1 (where R.sup.1 is H or C.sub.1-6 alkyl, preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), —SO.sub.2—C.sub.1-6 alkyl (preferably —SO.sub.2—C.sub.1-3 alkyl, e.g. —SO.sub.2—CH.sub.3), —SO.sub.2—NR.sup.2R.sup.3 (where R.sup.2 is H and R.sup.3 is optionally substituted phenyl), —NR.sup.4R.sup.5 (wherein R.sup.4 and R.sup.5 are independently selected from H, C.sub.1-6 alkyl (preferably C.sub.1-3 alkyl, e.g. —CH.sub.3), and —CO—C.sub.1-6 alkyl (preferably —CO—C.sub.1-3 alkyl, e.g. —CO—CH.sub.3), halogen (e.g. F, Cl or Br), and optionally substituted tetrazolyl; n is an integer from 0 to 5, preferably 0 to 2, e.g. 1 or 2; and denotes an E or Z double bond.

The present invention identifies AKR1C1 as the first lipedema-associated gene. The invention provides methods for diagnosing or assessing an individual's susceptibility to lipedema by the analysis of the AKR1C1 gene or the expression levels of its product and related metabolites. Also provided are therapeutic methods for treating a patient or methods for prophylactically treating an individual susceptible to lipedema.