Patent AU-2016206297-A1 (AU)
Title: Method to predict response to pharmacological chaperone treatment of diseases
Inventor: WUSTMAN BRANDON
IPC: A61K38/00
Filed: 2016-07-20
Abstract: The present invention provides methods to determine whether a patient with a 5 lysosomal storage disorder will benefit from treatment with a specific pharmacological chaperone. The present invention exemplifies an in vitro method for determining a-galactosidase A responsiveness to a pharmacological chaperone such as 1-deoxygalactonojirimycin in a cell line expressing a mutant from of a galactosidase A. The invention also provides a method for diagnosing Fabry disease 10 in patients suspected of having Fabry disease. Fig. 1A 1/36 Fabry Mutations Generated by Site-Directed Mutagenesis Missense L45R M72R R1 12H G147R G183S R227P D264V A285P Q312R R356G P4098 V390frX8 401isiaa Mil H46L M72V R112S S148N G183V R227Q 0264Y W287C D313G R356W P409T 401S MIK H46R A73V 'F113L S148R Y184C A230T P265L W287G D313Y 0357X T41DA de/20-24aa MIL H46Y M76R F113S Y152C M187T D231G P265R A288D V316E E58A T4101 de/13-8aa MIR W47G M76T 1117S 0155H M187V D231N D266E A288P 1317N E358G T410K del153aa MIT W47L WB1C R118C A156T L191P D231V D266H 1289F 1317T E358K T410P deJ205-7aa MIV D480 W81S L120P A156V L191Q 0234E D266N 1289S N3201 1359T G411D de/254aa A13P Ei48K G85D L120S A156Y T1941 D234Y D266V M2901 N320K G360C L414S de358aa L14P R49C G85M A121P W162C V199M S235C D266Y A291T N320Y G360D L415P ins247-8aa L16H R49G Y86C A121T W162G S201F S235F M2671 A292P Q321E G360S L33Y L16P R49L Y86D V124D W162R -S201Y W236C M267R A292T Q321L G361R L166G F18 R49P Y88D H125P G163V C202W W236L L268S P293A 0321R P362L H46S L19P R49S L89P S126G D165H C202Y W236R V269A P293H G3250 R363C 1124F A20P F50C L89R G128E D165V P205L S238N V269M P293S G325S R363H A31V M51i C90R L129P D165Y P205R 1239T 1270T P293T Q327E R363P L32P M51K 191T L131P D156Y P205S 1242F G271C F295C 27K L372P Complex D33Y C52G D92G G132E L166V P205T 1242N G271S M2961 G328A L372R D55V/Q57L N34K C52R D92H G132R L167P L206P L243F G271V M296V G328E G373D T N34S C52S DB2N Y134H K168N Y207C L243W N272K S297C G328R G373R Small G35R C52Y D92Y Y134S K168R Y207H D244N N272S S297F G328V G373S Ins/Del L36F L54P D93G A135V F169S Y207S C244H P273L N298H E338K A377D 19del5aa L36S D55V D93N D136H D170H N215D S247C L275F N298K V339E C378R 86deI6aa A37V C56F D93V D136Y D670V N215S S247P S276G N298S W340R C378Y 113delSaa 120del2aall P40L C56G C94S G138E G171C Y216C 0250P S276N D299G E341D C382W 120H 152inslaa/Y P40S C56Y C94Y G138R G171D Y216D 1253T 0279E L300F E341K C382Y 162D T411 Q57L W95L N139T G171R 1219N A257P Q279H L300H R342L 1384N 163dellaa M42L E59K W95S T1411 C172F C223G G258R Q279K L300P R342Q T385P 205del3aa M42R F60L A97P C142R C172G C223R G258V Q279R R301G L344P Q386p 20de17aa M42T C63Y A97V C142W C172R C223Y P259L Q280H R301P S345P P389R 254deliaa 281deliaaV M42V S65T R100K C142Y C172S N224D P259R 0280K R301Q A348P F396Y 281A G43D E6 RIOT A143P C172W N224S G260A 1282A 1303N W349R E398K 358dellaa G43R EB6K E103Q A143T C172Y H226D G261D T282N K308N A350P L403S 382delIaa G43S EB6Q LIO6R G144V C174G H225R W262C Q283P A309P A352D 1407K 403dellaa G43V L68F Q107L P146S G183A W226C N263S M284T L310F 1354K 1407R 247ins3aa W44C M7 R12C G14E G183D W226R D264A A285D 0312H N356K P409A 247ins8aa