WO2012023623A2 - Agent pour le traitement du syndrome de hunter - Google Patents

Agent pour le traitement du syndrome de hunter Download PDF

Info

Publication number
WO2012023623A2
WO2012023623A2 PCT/JP2011/068815 JP2011068815W WO2012023623A2 WO 2012023623 A2 WO2012023623 A2 WO 2012023623A2 JP 2011068815 W JP2011068815 W JP 2011068815W WO 2012023623 A2 WO2012023623 A2 WO 2012023623A2
Authority
WO
WIPO (PCT)
Prior art keywords
brain
administered
hi2s
sulfatase
therapeutic agent
Prior art date
Application number
PCT/JP2011/068815
Other languages
English (en)
Japanese (ja)
Other versions
WO2012023623A3 (fr
Inventor
義勝 衞藤
孝 樋口
十也 大橋
Original Assignee
日本ケミカルリサーチ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 日本ケミカルリサーチ株式会社 filed Critical 日本ケミカルリサーチ株式会社
Publication of WO2012023623A2 publication Critical patent/WO2012023623A2/fr
Publication of WO2012023623A3 publication Critical patent/WO2012023623A3/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/06—Sulfuric ester hydrolases (3.1.6)
    • C12Y301/06013—Iduronate-2-sulfatase (3.1.6.13)

Definitions

  • the present invention relates to a therapeutic agent for Hunter syndrome, and more particularly to a therapeutic agent containing human iduronic acid 2-sulfatase for preventing progression of brain damage associated with Hunter syndrome.
  • Hunter syndrome is a genetic disease caused by a gene mutation of iduronic acid 2-sulfatase (I2S), and is a kind of lysosomal disease.
  • I2S has an activity of hydrolyzing the sulfate ester bond of heparan sulfate and dermatan sulfate belonging to glycosaminoglycan.
  • mutations in the enzyme cause abnormal metabolism of the substrates heparan sulfate and dermatan sulfate, and these incomplete degradation products accumulate in systemic tissues, resulting in skeletal abnormalities and cardiac enlargement.
  • Hunter syndrome includes a severe type (IIA type) with a relatively short clinical course and a rapid progression, and a mild type (IIB type) with a very long course.
  • the two types, severe (type IIA) and mild (type IIB) are caused by differences in the mutation type of the I2S gene.
  • the former has a poor prognosis and dies by the age of 15-16. It was already known in the 1970s that the activity of I2S was low in Hunter syndrome patients, and it was expected that this disease was due to a congenital deficiency of I2S.
  • Non-patent Document 1 The existence of the I2S gene on the X chromosome has long been predicted because the disease is inherited, but in 1990, a group of Hopwood et al. Of Women's and Children's Hospital in Australia purchased the enzyme. We succeeded in isolating the encoded gene, and proved again that the mutation of this enzyme is the cause of Hunter's syndrome (Non-patent Document 1). As mentioned above, since Hunter syndrome was expected to be caused by I2S deficiency, therapy by supplementation of this enzyme for Hunter syndrome patients was started in the 1970s, and transplantation of macrophages expressing this enzyme was started. (Non-Patent Document 2) and supplementation of this enzyme by instillation of normal serum (Non-Patent Document 3) have been attempted for patients.
  • the dosage is 0.5 mg / kg body weight once a week by intravenous infusion. It has become. Hunter syndrome may be associated with intellectual disability, and severe brain disorders such as brain atrophy and hydrocephalus may be observed.
  • I2S which is a high molecular weight protein, can hardly reach the brain due to the blood-brain barrier when administered intravenously. Therefore, the intravenous administration of I2S has a problem that an effective treatment for a brain disorder of a Hunter syndrome patient cannot be expected.
  • Patent Document 1 A method of administering human ⁇ -L-iduronidase into the medullary cavity of a patient with Hurler's syndrome (mucopolysaccharidosis type I) in order to cope with a brain disorder associated with lysosomal disease (Patent Document 1), a patient with Niemann-Pick disease A method of administering human acid sphingomyelinase into the ventricle (Patent Document 2) has been reported. However, there are no reports on specific ways of dealing with brain damage in Hunter syndrome patients. Special table 2007-504166 Special table 2009-525963 Wilson PJ et al. Proc Natl Acad Sci USA (1990) 87, 8531-5. Dean MF et al. , J Clin Invest. (1979) 63, 138-45 Brown FR 3rd et al. , Am J Med Genet. (1982) 13, 309-18
  • an object of the present invention is to provide a method of supplying human iduronic acid 2-sulfatase (hI2S) into a patient's brain in order to prevent progression of brain damage in a patient with Hunter syndrome.
  • hI2S human iduronic acid 2-sulfatase
  • the present inventors have found that by administering hI2S into the ventricle of the knockout mouse lacking the I2S gene, the I2S activity in the brain can be increased and maintained. completed. That is, the present invention provides the following.
  • a therapeutic agent for Hunter syndrome comprising human iduronic acid 2-sulfatase as an active ingredient, which is administered into the human ventricle.
  • the therapeutic agent according to (1) above wherein the Hunter syndrome is accompanied by a brain disorder.
  • the therapeutic agent according to (1) or (2) which is administered using an indwelling cannula, an indwelling catheter, or an indwelling needle.
  • I2S activity in the brain can be increased and maintained, and heparan sulfate and dermatan sulfate accumulated in the brain can be decomposed and eliminated.
  • human iduronic acid 2-sulfatase means not only wild-type human iduronic acid 2-sulfatase but also one or more amino acids constituting human iduronic acid 2-sulfatase as long as it has biological activity. Also included are analogs of human iduronic acid 2-sulfatase with residues substituted, deleted, or inserted. hI2S is also synonymous. Human iduronic acid 2-sulfatase (hI2S) can be produced using genetic recombination techniques. For example, hI2S is produced in a culture solution or in a host cell by incorporating a gene encoding hI2S into an expression vector and culturing the transformed host cell.
  • a patient with Hunter syndrome to be treated is not particularly limited, but is particularly a patient with a brain disorder. Brain disorders include intellectual disability, brain atrophy, hydrocephalus and the like.
  • the scalp is incised, then a hole is made in the skull, and a long injection needle, such as a catalan needle, is inserted into the hole and administered into the ventricle.
  • a long injection needle such as a catalan needle
  • an indwelling needle, a cannula for indwelling, or an indwelling catheter can be installed in the hole, and can be administered into the ventricle at a desired timing through them.
  • the amount of human iduronic acid 2-sulfatase administered into the ventricle is preferably 10 to 800 ⁇ g / kg body weight, more preferably 100 to 800 ⁇ g / kg body weight, still more preferably 100 to 600 ⁇ g / kg. It is weight.
  • the administration interval is preferably every 3 weeks to 2 months, more preferably 3 weeks.
  • the dosing interval can be adjusted as appropriate once every 2 weeks to 6 months according to the patient's symptoms.
  • the therapeutic agent of the present invention can be supplied to a medical institution as a lyophilized product or as an aqueous liquid.
  • human iduronic acid 2-sulfatase dissolved in a solution containing a stabilizer, a buffer, and an isotonic agent can be supplied as a preparation sealed in a vial or a syringe.
  • a preparation enclosed in a syringe is generally called a prefilled syringe preparation.
  • the concentration of human iduronic acid 2-sulfatase contained in the aqueous solution is preferably 1 to 4 mg / mL, more preferably 2 to 3 mg / mL.
  • the stabilizer contained in the aqueous liquid is not particularly limited as long as it is pharmaceutically acceptable, but a nonionic surfactant can be preferably used.
  • a nonionic surfactant polysorbate, poloxamer, etc. can be used alone or in combination.
  • Polysorbate 20 and polysorbate 80 are particularly suitable as the polysorbate, and poloxamer 188 (polyoxyethylene (160) polyoxypropylene (30) glycol) is particularly suitable as the poloxamer.
  • the concentration of the nonionic surfactant contained in the aqueous liquid is preferably 0.01 to 1 mg / mL, more preferably 0.01 to 0.5 mg / mL, More preferably, it is 0.5 mg / mL.
  • the buffer contained in the aqueous liquid is not particularly limited as long as it is pharmaceutically acceptable, but a phosphate buffer is preferable, and a sodium phosphate buffer is particularly preferable.
  • the concentration of sodium phosphate is preferably 0.01 to 0.04M.
  • the pH of the aqueous liquid preparation adjusted with a buffer is preferably 5.5 to 7.2.
  • the isotonic agent contained in the aqueous solution is not particularly limited as long as it is pharmaceutically acceptable, but sodium chloride and mannitol can be used preferably alone or in combination.
  • the therapeutic agent of the present invention can improve convenience in a medical institution by distributing it as a kit preparation packaged together with a dedicated injection needle used for its administration, for example, a cattelan needle.
  • hI2S was prepared by referring to a well-known method for culturing CHO cells transformed with the hI2S gene (US Pat. No. 5,932,211).
  • a 21-week-old male mouse was placed in an anesthesia bottle filled with diethyl ether and anesthetized by inhalation, and then 200-300 ⁇ L of Nembutal injection solution (Dainippon Pharmaceutical) diluted 10-fold was added to the mouse using a 30-gauge needle. It was administered subcutaneously and completely anesthetized.
  • a brain fixing tool which is an accessory member of the brain stereotaxic apparatus (Narumo Scientific Instruments Laboratory, Type SR-5)
  • the mouse was fixed to the brain stereotaxic apparatus.
  • the hair of the mouse head was cut off with a scissors to expose the scalp.
  • the scalp was disinfected with isodine, and in the presence of an enlarged loupe, the scalp was incised with a scissors to expose the intersection of coronary and sagittal sutures (Bregma).
  • a hole with a diameter of 0.5 mm was drilled in the skull at a position 3 mm deep and 2 mm left from the pegma using a catalan needle 18G (Terumo Corporation), and this was used as an access point.
  • 20 ⁇ g (67 ⁇ L) of hI2S was administered to a position 3 mm deep from the access point over about 30 seconds.
  • a microsyringe for Ito microsyringe 10 ⁇ L: model number ITS MS-NG10, Ito Seisakusho Co., Ltd.
  • an injection needle for compatible needle Ito microsyringe 30G 20 mm 22 degrees, Ito Seisakusho Co., Ltd.
  • the needle was fixed for 1 minute, then slowly pulled out 1.5 mm, where it was fixed for another 1 minute, and then slowly and completely removed.
  • 6.7 ⁇ L of physiological saline was administered to the control group in the same manner. After disinfecting the incision with isodine, the scalp was pasted together with an instantaneous adhesive (Aron Alpha A, Daiichi Sankyo).
  • mice Prior to administration of hI2S, mice were weighed and the dose of hI2S per kg body weight was calculated.
  • the dose of hI2S was the average of 3 animals in the hI2S administration group, the first time (at 21 weeks of age) 698.7 ⁇ g / kg body weight, the second time (at 24 weeks of age) 661.2 ⁇ g / kg body weight, the third time ( 27 weeks old) was 681.8 ⁇ g / kg body weight, and the fourth time (30 weeks old) was 6452 ⁇ g / kg body weight.
  • mice Three weeks after the final administration (33 weeks of age), the mouse was dissected and the tissue was removed. The mouse was placed in an anesthesia bottle filled with diethyl ether and inhaled and anesthetized. Then, the chest of the mouse was incised to cut the right atrial appendage, and then a winged needle (Terumo winged needle 27G X 1/2, Terumo) was inserted into the right ventricle. ) And 1 XD-PBS (-) (Wako Pure Chemical Industries) was slowly refluxed using a 50 mL syringe (Terumo syringe 50 mL, Terumo).
  • the brain, eyes, lungs, heart, liver, kidney, spleen and testis were removed. After removal, the brain was divided into anterior cerebrum, posterior cerebrum and cerebellum. Each tissue was weighed and then enclosed in a sample tube and stored in liquid nitrogen. [Measurement of human iduronic acid 2-sulfatase activity] Frozen organs were thawed, 20 mg each was weighed and placed in a 1.5 mL sampling tube.
  • the amount of liquid containing 15 ⁇ g of protein was calculated for each supernatant, and the amount of liquid was collected in 0.2 mL tubes.
  • a substrate solution (1.25 mM 4-methylbelliferyl- ⁇ -L-iduronide-2-sulfate (MU- ⁇ Idu-2S, Moscerdam Substrates)
  • a substrate buffer 0.1 M Na-acetate / acetic acid buffer, 10 mM.
  • Pi / Ci Bafa (0.4M Na 2 HPO 4, 0.2M C 6 H 5 Na 3 O 7 .2H 2 O, 0.02% (w / v) NaN 3 (pH4.5)) and 40 ⁇ L is added Further, 10 ⁇ L of LEBT (bovine testis-derived purified lysosomal enzyme, Moscerdam Substrates) was added and stirred, and the mixture was allowed to stand at 37 ° C. for 24 hours for reaction (second reaction). After standing, the entire amount of the reaction solution was transferred to an RIA tube (RIA tube 3, Hirose Sangyo), and a stop buffer (0.5 M NaHCO 3 / Na 2 CO 3 buffer, 0.025% Triton X-100 (pH 10) was added thereto.
  • LEBT bovine testis-derived purified lysosomal enzyme, Moscerdam Substrates
  • the hI2S administration group When comparing the iduronic acid 2-sulfatase activity in the brain between the hI2S administration group and the control group administered with physiological saline, the hI2S administration group is about 60 times more in the cerebellum than the control group, and about 500 in the forebrain and hindbrain. The activity was ⁇ 1000 times. Since the measurement of enzyme activity is performed 3 weeks after the last administration of the enzyme, this result shows that hI2S administered into the ventricle continues its enzyme activity in the brain for more than 3 weeks after administration. Show.
  • the enzyme activity of can be maintained equal to or higher than that of the wild type.
  • the administration schedule of hI2S administered every 3 weeks in the amount of 600 to 700 ⁇ g / kg body weight per application is also applied to humans as it is it can.
  • the enzyme activity in the forebrain and hindbrain is three times that of the wild type in the hI2S administration group, and it is sufficient that the enzyme activity in the brain rises to the wild type level in order for hI2S to exert a therapeutic effect. In view of this, even if the dose per administration is about 10 to 600 ⁇ g / kg body weight, a sufficient therapeutic effect can be obtained.
  • the administration interval can be 3 weeks or more, for example, every 1 to 2 months.
  • the enzyme activity of the hI2S administration group is approximately 0.7 to 1.7 times that of the wild type, and by administering hI2S into the ventricle , HI2S was found to be efficiently taken up by other organs. This indicates that the intraventricular administration of hI2S is extremely excellent as a means for systemically administering hI2S to patients with Hunter syndrome.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Zoology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Psychiatry (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Hospice & Palliative Care (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

La présente invention concerne un procédé pour distribuer de l'iduronate-2-sulfatase humaine dans le cerveau d'un patient afin de prévenir la progression d'une lésion cérébrale chez des patients ayant le syndrome de Hunter. Le procédé est caractérisé en ce qu'un agent de traitement contenant de l'iduronate-2-sulfatase humaine est administré dans le cerveau d'un patient ayant le syndrome de Hunter.
PCT/JP2011/068815 2010-08-19 2011-08-15 Agent pour le traitement du syndrome de hunter WO2012023623A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2010-200310 2010-08-19
JP2010200310 2010-08-19

Publications (2)

Publication Number Publication Date
WO2012023623A2 true WO2012023623A2 (fr) 2012-02-23
WO2012023623A3 WO2012023623A3 (fr) 2012-04-12

Family

ID=45605484

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2011/068815 WO2012023623A2 (fr) 2010-08-19 2011-08-15 Agent pour le traitement du syndrome de hunter

Country Status (2)

Country Link
JP (1) JP2012062312A (fr)
WO (1) WO2012023623A2 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2593131A2 (fr) * 2010-06-25 2013-05-22 Shire Human Genetic Therapies, Inc. Procédés et compositions pour la délivrance au snc d'iduronate-2-sulfatase
US9220677B2 (en) 2010-06-25 2015-12-29 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of iduronate-2-sulfatase
US9283181B2 (en) 2010-06-25 2016-03-15 Shire Human Genetic Therapies, Inc. CNS delivery of therapeutic agents
US9320711B2 (en) 2010-06-25 2016-04-26 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of heparan N-sulfatase
US9770410B2 (en) 2010-06-25 2017-09-26 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of arylsulfatase A
KR20190097067A (ko) 2016-12-26 2019-08-20 쿄와 기린 가부시키가이샤 미엘린 올리고덴드로사이트 당단백질에 결합하는 항체
WO2020004490A1 (fr) 2018-06-26 2020-01-02 協和キリン株式会社 Anticorps se liant au protéoglycane-5 à chondroïtine sulfate
WO2020004492A1 (fr) 2018-06-26 2020-01-02 協和キリン株式会社 Anticorps se liant à la molécule d'adhésion cellulaire 3
US10660944B2 (en) 2011-12-23 2020-05-26 Shire Human Genetic Therapies, Inc. Stable formulations for CNS delivery of arylsulfatase A
US12121569B2 (en) 2022-01-18 2024-10-22 Takeda Pharmaceutical Company Limited Methods and compositions for CNS delivery of iduronate-2-sulfatase

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9994641B2 (en) 2013-12-25 2018-06-12 Jcr Pharmaceuticals Co., Ltd. Anti-human transferrin receptor antibody that passes through blood-brain barrier
JP6914193B2 (ja) 2015-06-24 2021-08-04 Ｊｃｒファーマ株式会社 Ｂｄｎｆを含む融合蛋白質
MX2018000305A (es) 2015-06-24 2018-03-14 Japan Chem Res Anticuerpo anti-receptor de transferrina humana que penetra la barrera hematoencefalica.
BR112018013421A2 (pt) 2015-12-30 2018-12-18 Green Cross Corp métodos e composições para tratar a síndrome de hunter
EP3560958A4 (fr) 2016-12-26 2020-08-12 JCR Pharmaceuticals Co., Ltd. Nouvel anticorps anti-récepteur de la transferrine humaine capable de pénétrer dans la barrière hémato-encéphalique
US20200384061A1 (en) 2016-12-26 2020-12-10 Jcr Pharmaceuticals Co., Ltd. Fusion Protein Including BDNF
KR102671857B1 (ko) * 2018-05-30 2024-06-04 주식회사 녹십자 대뇌 측뇌실 투여에 의해 헌터증후군을 치료하기 위한 방법 및 조성물

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009525963A (ja) * 2006-01-20 2009-07-16 ジェンザイム・コーポレーション リソソーム蓄積症のための脳室内酵素の輸送

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7442372B2 (en) * 2003-08-29 2008-10-28 Biomarin Pharmaceutical Inc. Delivery of therapeutic compounds to the brain and other tissues

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009525963A (ja) * 2006-01-20 2009-07-16 ジェンザイム・コーポレーション リソソーム蓄積症のための脳室内酵素の輸送

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
COOK, A.M. ET AL.: 'Intracerebroventricular administration of drugs' PHARMACOTHERAPY vol. 29, no. 7, 2009, pages 832 - 45 *
IDENSHI KUMIKAE MUKO TATOSHO II-GATA CHIRYOZAI ELAPRASE TENTEKI SEICHUEKI 6MG TENPU BUNSHO 2008, *
PAN, J. ET AL.: 'Widespread correction of brain pathology in Hunter mice after an intracerebral injection of idursulfase' ACTA PAEDIATRICA vol. 97, no. 457, 2008, page 103 *
TAKASHI HIGUCHI ET AL.: 'MPSII-gata Knockout Mouse de no Noshitsu Nai Koso Chiryo ni Kansuru Kenkyu' JAPANESE JOURNAL FOR INHERITED METABOLIC DISEASES vol. 26, no. 2, 24 September 2010, page 82 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10646554B2 (en) 2010-06-25 2020-05-12 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of arylsulfatase A
US11260112B2 (en) 2010-06-25 2022-03-01 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of iduronate-2-sulfatase
EP2593131A2 (fr) * 2010-06-25 2013-05-22 Shire Human Genetic Therapies, Inc. Procédés et compositions pour la délivrance au snc d'iduronate-2-sulfatase
US9283181B2 (en) 2010-06-25 2016-03-15 Shire Human Genetic Therapies, Inc. CNS delivery of therapeutic agents
US11471516B2 (en) 2010-06-25 2022-10-18 Shire Human Genetic Therapies, Inc. CNS delivery of therapeutic agents
US9770410B2 (en) 2010-06-25 2017-09-26 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of arylsulfatase A
US9814764B2 (en) 2010-06-25 2017-11-14 Shire Human Genetic Therapies, Inc. Treatment of sanfilippo syndrome type b by intrathecal administration of alpha-n-acetylglucosaminidase
EP3964229A1 (fr) * 2010-06-25 2022-03-09 Shire Human Genetic Therapies, Inc. Procédés et compositions pour l'administration d'iduronate-2-sulfatase au système nerveux central
US10456454B2 (en) 2010-06-25 2019-10-29 Shire Human Genetic Therapies, Inc. CNS delivery of therapeutic agents
EP2593131A4 (fr) * 2010-06-25 2014-01-22 Shire Human Genetic Therapies Procédés et compositions pour la délivrance au snc d'iduronate-2-sulfatase
US11065307B2 (en) 2010-06-25 2021-07-20 Shire Human Genetic Therapies, Inc. Therapeutic fusion protein comprising an alpha-n-acetylglucosaminidase and a lysosomal targeting moiety
EP3626258A1 (fr) * 2010-06-25 2020-03-25 Shire Human Genetic Therapies, Inc. Procédés et compositions pour l'administration d'iduronate-2-sulfatase au système nerveux central
US9220677B2 (en) 2010-06-25 2015-12-29 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of iduronate-2-sulfatase
US9320711B2 (en) 2010-06-25 2016-04-26 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of heparan N-sulfatase
US11065308B2 (en) 2010-06-25 2021-07-20 Shire Human Genetic Therapies, Inc. Methods and compositions for CNS delivery of heparan n-sulfatase
US10660944B2 (en) 2011-12-23 2020-05-26 Shire Human Genetic Therapies, Inc. Stable formulations for CNS delivery of arylsulfatase A
KR20190097067A (ko) 2016-12-26 2019-08-20 쿄와 기린 가부시키가이샤 미엘린 올리고덴드로사이트 당단백질에 결합하는 항체
US11117963B2 (en) 2016-12-26 2021-09-14 Kyowa Hakko Kirin Co., Ltd. Antibody which binds to myelin oligodendrocyte glycoprotein
KR20210027295A (ko) 2018-06-26 2021-03-10 쿄와 기린 가부시키가이샤 세포 부착 분자3에 결합하는 항체
WO2020004492A1 (fr) 2018-06-26 2020-01-02 協和キリン株式会社 Anticorps se liant à la molécule d'adhésion cellulaire 3
WO2020004490A1 (fr) 2018-06-26 2020-01-02 協和キリン株式会社 Anticorps se liant au protéoglycane-5 à chondroïtine sulfate
KR20210025023A (ko) 2018-06-26 2021-03-08 쿄와 기린 가부시키가이샤 콘드로이틴 황산 프로테오글리칸-5에 결합하는 항체
US11873337B2 (en) 2018-06-26 2024-01-16 Kyowa Kirin Co., Ltd. Antibody binding to cell adhesion molecule 3
US11965035B2 (en) 2018-06-26 2024-04-23 Kyowa Kirin Co., Ltd. Antibody binding to chondroitin sulfate proteoglycan 5
US12121569B2 (en) 2022-01-18 2024-10-22 Takeda Pharmaceutical Company Limited Methods and compositions for CNS delivery of iduronate-2-sulfatase

Also Published As

Publication number Publication date
WO2012023623A3 (fr) 2012-04-12
JP2012062312A (ja) 2012-03-29

Similar Documents

Publication Publication Date Title
WO2012023623A2 (fr) Agent pour le traitement du syndrome de hunter
JP6952831B2 (ja) ポンペ病の処置のための高濃度α−グルコシダーゼ組成物
US12076376B2 (en) Methods for treating lysosomal acid lipase deficiency in patients
JP6858231B2 (ja) ハンター症候群治療剤および治療方法
US10966962B2 (en) Method for treating neurodegenerative diseases
US20210198691A1 (en) Compositions and methods for the treatment of parkinson's disease
ES2953560T3 (es) Procedimiento para el tratamiento o reducción de paniculopatía fibrosclerótica edematosa
EA007967B1 (ru) Защита, восстановление и усиление эритропоэтинреактивных клеток, тканей и органов
US11814658B2 (en) Lipid-encapsulated dual-cleaving endonuclease for DNA and gene editing
US20210121484A1 (en) Inhibitors of enpp1 and methods of using same
NIEUWENHUIS et al. 1-Desamino-8-D-arginine vasopressin (desmopressin) shortens the bleeding time in storage pool deficiency
JP2019506439A (ja) ターゲティングされた治療用リソソーム酵素融合タンパク質、関連する製剤、およびその使用
JP6987924B2 (ja) ハンター症候群を治療するための方法および組成物
Tanpaiboon Practical management of lysosomal storage disorders (LSDs)
US20100143321A1 (en) Therapeutic composition for interstitual pneumonia
KR20110094321A (ko) 수식형 수퍼옥사이드 디스뮤타아제 함유 흡입제
US20230321196A1 (en) Medicine for Preventing or Treating Symptom or Disorder in Subject Affected by Viral Infection
CN108310369B (zh) 一种用于经皮冠状动脉介入治疗的给药系统
Vaishnavi et al. CASE REPORT ON HUNTER SYNDROME: A REVIEW
Chattopadhyay et al. Chemical Chaperones to Treat Protein Diseases
Gregoriadis Liposomes as Carriers of Proteins: Possible Medical Applications
KR20130136990A (ko) 환자에서 리소좀 산 리파제 결핍증의 치료를 위한 리소좀 산 리파제의 용도

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11818263

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11818263

Country of ref document: EP

Kind code of ref document: A2