US 11,944,628 B2
Methods for the use of low-dose immune modulators transiently for treating patients undergoing protein replacement therapy
Priya S. Kishnani, Durham, NC (US); Zoheb B. Kazi, Durham, NC (US); and Ankit K. Desai, Durham, NC (US)
Assigned to Duke University, Durham, NC (US)
Appl. No. 16/612,976
Filed by Duke University, Durham, NC (US)
PCT Filed May 11, 2018, PCT No. PCT/US2018/032422
§ 371(c)(1), (2) Date Nov. 12, 2019,
PCT Pub. No. WO2018/209300, PCT Pub. Date Nov. 15, 2018.
Claims priority of provisional application 62/505,244, filed on May 12, 2017.
Prior Publication US 2020/0078361 A1, Mar. 12, 2020
Int. Cl. A61P 37/02 (2006.01); A61K 31/519 (2006.01); A61K 38/47 (2006.01)
CPC A61K 31/519 (2013.01) [A61K 38/47 (2013.01); A61P 37/02 (2018.01)] 17 Claims
 
1. A method of inducing immune tolerance in a human subject suffering from Pompe disease, the method comprising:
(i) administering via infusion to a human treatment-naive subject a therapeutically effective amount of recombinant human alglucosidase alfa (rhGAA) as enzyme replacement therapy (ERT), and
(ii) administering to the subject an immune tolerance induction protocol,
wherein the immune tolerance induction protocol does not comprise administration of intravenous gamma globulin (IVIG), rituximab, or bortezomib prior to step (i);
wherein the immune tolerance induction protocol consists of a three-day cycle of methotrexate,
wherein the first day of the three-day cycle of methotrexate is the day of rhGAA administration,
wherein a dose of methotrexate comprises about 0.1 mg/kg body weight to about 0.6 mg/kg body weight per day,
wherein the methotrexate is administered either orally about one hour before the rhGAA administration or subcutaneously about 15 minutes before the rhGAA administration; and
(iii) repeating (i) and (ii) at least three times so that the subject begins a three-day cycle of methotrexate with each of the first four rhGAA infusions;
wherein, by following step (ii) and step (iii), immune tolerance to rhGAA is induced in the subject.