Treatment of mucopolysaccharidosis type I using fully human glycosylated human α-L-iduronidase (IDUA)

Abstract

We provide treatment for mucopolysaccharidosis type 1 (MPS I). [Solution] A method for treating a human subject diagnosed with MPS I, comprising delivering a therapeutically effective amount of recombinant human IDUA produced by human nerve cells to the cerebrospinal fluid of the brain of the human subject, wherein the human IDUA is delivered by administration of a recombinant nucleotide expression vector encoding human IDUA, the recombinant nucleotide expression vector is administered in a dose corresponding to the brain mass of the human subject, and the brain mass is determined by magnetic resonance imaging of the brain of the subject.

Claims

1. A treatment method for a human being diagnosed with mucopolysaccharidosis type 1 (MPS I), wherein the human The cerebrospinal fluid of the target brain was treated with a therapeutically effective amount of recombinant human α-L-Izulo produced by human nerve cells. The process includes delivering nidase (IDUA), wherein the human IDUA is coated The recombinant nucleotide is delivered by administration of a recombinant nucleotide expression vector, and the recombinant nucleotide The expression vector is administered in a dose corresponding to the brain mass of the human subject, and the brain mass is the same as the The method is determined by magnetic resonance imaging (MRI) of an elephant's brain.

2. A treatment method for a human subject diagnosed with MPS I, comprising the cerebrospinal fluid of the brain of the human subject. This includes delivering a therapeutically effective amount of recombinant human IDUA produced by human glial cells, The aforementioned human IDUA is administered via a recombinant nucleotide expression vector encoding the human IDUA. The recombinant nucleotide expression vector is delivered by the human subject according to the brain mass. The method wherein the brain mass is determined by a brain MRI of the subject's brain, administered in a specified dose.

3. The brain mass of the human subject is the brain volume of the human subject in cm². ３ 1.046 g / cm³ ３ The person in charge Multiplying by a number, the brain volume of the human subject is converted, and the brain volume of the human subject is compared to the human The method according to claim 1 or 2, obtained from an elephant brain MRI.

4. The recombinant nucleotide expression vector is approximately 2 × 10 ９ GC / g brain mass, approximately 1×10 １ ０ GC / g brain mass, or approximately 5 × 10⁻⁶ １０ Claim 1, administered in a dose equal to GC / g brain mass. The method described in any one of items (3) above.

5. The recombinant nucleotide expression vector is administered via intracision (IC) administration. The method described in any one of the requests 1 to 4.

6. The recombinant nucleotide expression vector is administered via intraventricular (ICV) administration. The method according to any one of claims 1 to 4.

7. The recombinant nucleotide expression vector exceeds 10% of the total cerebrospinal fluid volume of the human subject. The method according to any one of claims 1 to 6, administered in an empty volume.

8. Before or simultaneously with the human IDUA treatment, the human subject Claims 1 to 1 further include administering immunosuppressive therapy and continuing immunosuppressive therapy thereafter. The method described in any one of item 7.

9. The immunosuppressive therapy is administered before or at the same time as the human IDUA treatment. Sometimes, (a) tacrolimus and mycophenolic acid, (b) rapamycin and mycopheno (c) tacrolimus, rapamycin, and corticosteroids, for example, The combination of rednisolone and / or methylprednisolone is administered to the human subjects. The method according to claim 8, comprising giving and continuing thereafter.

10. The method according to claim 8 or 9, wherein the immunosuppressive therapy is discontinued after 180 days.

11. The human IDUA comprises the amino acid sequence of SEQ ID NO: 1, any one of claims 1 to 10. The method described in section [section number].

12. The recombinant nucleotide expression vector is administered in the doses listed in the table below, according to the request. The method described in any one of items 1 to 11. Table 1

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