ШАЧМЕН Эдвард Х. (US),ДЕСНИК Роберт Дж. (US),КОКС Джеральд Ф. (US),ЭНДРЮС Лора П. (US),МЮРРЕЙ Джеймс М. (US)
申请号：
RU2012111823/15
公开号：
RU2012111823A
申请日:
2010.08.28
申请国别(地区):
RU
年份:
2013
代理人:
摘要：
1. A method of treating a human subject having acid sphingomyelinase deficiency, comprising: (a) a regimen for reducing the mass of accumulated sphingomyelin substrate, comprising: (i) administering an initial low non-toxic dose of acid sphingomyelinase (ASM)； (ii) administering sequentially higher doses ASM and subject monitoring for one or more unwanted side effects after each subsequent dose, which is indicated by increased bilirubin or an associated adverse event； and (b) a maintenance regimen comprising administering a dose of ASM equal to or less than the highest dose tolerated by the subject as a maintenance dose to the subject. The method of claim 1, wherein the ASM is rhASM. 3. The method according to claim 2, in which the initial dose range is from 0.1 mg / kg to 1 mg / kg or from 0.1 mg / kg to 0.5 mg / kg rhASM. The method of claim 3, wherein the initial dose is 0.1 mg / kg rhASM. 5. A method according to any one of claims 1 to 4, wherein successively higher doses are administered one, two, three or four weeks after the previous dose. The method of claim 5, wherein the sequentially higher dose is about 0.1-1.0 mg / kg higher than the previous dose or about 0.1-0.5 mg / kg higher than the previous dose. A method according to any one of claims 1 to 4, wherein the highest dose tolerated by the human subject is from 1 mg / kg to 3 mg / kg. A method according to any one of claims 1 to 4, wherein the highest tolerated dose is administered to a human subject as a maintenance dose. The method of claim 7, wherein the highest tolerated dose is administered to a human subject as a maintenance dose. The method according to any one of claims 1 to 4, in which the maintenance dose is therapeutically effective1. Способ лечения субъекта-человека, имеющего недостаточность кислой сфингомиелиназы, включающий:(a) схему для сокращения массы накопленного субстрата сфингомиелина, включающую:(i) введение начальной низкой нетоксичной дозы кислой сфингомиелиназы (ASM)；(ii) введени
