Patent AU-2019219727-B2 (AU)
Title: Method to predict response to pharmacological chaperone treatment of diseases
Inventor: WUSTMAN BRANDON
IPC: A61K38/00
Filed: 2019-08-20
Granted: 2021-05-20
Abstract: The present invention provides methods to determine whether a patient with a 
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 in patients suspected of having Fabry disease.
Fig. 1A 1/36 
Fabry Mutations Generated by Site-Directed Mutagenesis 
Mlssense L45R M72R RI12H G147R G183S R227P D264V A2865P 0312R R356G P409S V390frX8 
401inslaa 
M1l H46L M72V R112S S148N G183V R227Q 0264Y W287C D313G R356W P409T 4016 
MIK H46R A73V 'F113L S148R Y184C A230T P265L W287G D313Y 0357X T410A de20-24as 
M1L H46Y M76R F1133 Y152C M187T D231G P265R A288D V316E E358A T4101 del13-8aa 
MIR W47G M76T 1117S DISSH M187V 0231N D266E A288P B17N E358G T410K del153aa 
MIT W47L W1C R118C A156T L191P D231V D266H 1289F 017T E358K T410P deI205-7aa 
MiV E48D W81S L120P A156V L191Q D234E D266N 1289S N3201 O5T G411D de/254aa 
A13P E48K G85D L120S A156Y T1941 D234Y D266V M2901 N320K G360C L414S del358aa 
L14P R49C G85M A121P M62C V199M S235C 0266Y A291T N320Y G360D L41§P ins247-8ea 
L16H R49G Y6C_ A121T W162G S201F S236F 12671 A292P Q321E G360S L33Y 
L16P R49L Y86D V124D W162R S201Y W236C M267R A292T 0321L G361R L166G 
FIBS R49P Y86D H126P G163V C202W W236L L268S P293A Q321R P362L H46S 
L19P R49S L89P S126G 0165H C202Y W236R V269A P293H G325D R363C 1124F 
A20P F60C LS9R G128E D16V R205L S238N V269M P293S G325S R363H 
A31V M511 C0R L129P D165Y P205R 1239T 1270T P293T Q327E R363P 
L32P M51K 191T L131P D156Y P205S 1242 G271C F295C O37 L372P Complex 
D33Y C52G D92G G132E L166V P205T 1242N G271S M2961 G328A L372R D55V/Q57L 
L120PIA121 
N34K C52R D92H G132R L167P L206P L243F G271V M296V G328E G373D T 
N345 C52S D92N Y134H K168N Y207C L243W N272K S297C G328R G373R 
Small 
G35R C52Y D92Y Y1348 K168R Y207H 0244N N272S S297F G328V G373S Ins/Del 
L36F L54P 093G A135V F169S Y207S 0244H F273L N298H E338K A377D 19delfaa 
L36S D55V D93N D136H DITCH N215D S247C L275F N298K V339E C378R 6Sdel6aa 
A37V C56F D93V D136Y D170V N215S S247P S276G N298S W340R C378Y 113del8aa 
120del2aalL 
P40L C56G C94S G138E G171C Y216C 0250P S276N 0299G E341D C382W 120H 
1521nslaafY 
P40S C56Y C94Y G138R G1710 Y216D t253T 0279E L300F E341K C382Y 1620 
T411 057L W95L N39T G171R 219N A257P Q279H L300H R342L 1384N 153delIaa 
M42L E59K W95S T1411 C172F C223G G2568R L300P R3420 T385P 205del3aa 
M42R F60L A97P C142R C172G C223R G258V Q279R R301G L344P Q386P 205del7aa 
M42T C63Y A97V C142W U172R C223Y P259L Q280H R301P S345P PMR 254dellaa 
281dehlaafV 
M42V S65T RIOOK C142Y C172S N224D P259R 0280K R3010 A348P F396Y 281A 
G43D E56G RIOT A143P C172W N224S G260A T282A 1303N W349R E398K 3S8deIlaa 
G43R EB6K 6103Q A143T C172Y H226D G261D T282N K308N A360P L403S 382deIlaa 
043$ E56Q L16R G144V C174G H225R W2,7 Q283P A3091 A352D 1407K 403dellaa 
G43V L68F Q107L P146S G183A W226C N263S M284T L310F 1354K 1407R 247ins3aa 
W44 M721 R112C 147 G183D W226R D264A A286D 0312H N3565K P409A 247insaa