IP Library › Granted Patent US 12,644,122
Granted Patent B2
US 12,644,122 · App. 17/710,418 · Granted Jun 2, 2026

Compositions and methods for treating amyotrophic lateral sclerosis

Inventors: Alessandra Biffi (Boston, MA); Marco Peviani (Boston, MA); Francisco J. Molina-Estevez (Boston, MA)
Assignees: The Children's Medical Center Corporation; Dana-Farber Cancer Institute, Inc.
C12N15/1137A61K35/28A61P25/28C12N2310/141C12N2310/531
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Quick Facts
Patent No.
US 12,644,122
App. No.
17/710,418
Granted
Jun 2, 2026
Kind
B2
Abstract

The present disclosure features methods and compositions for treating amyotrophic lateral sclerosis (ALS). The disclosed methods comprise administering to a subject having or suspected of having ALS a hematopoietic stem progenitor cell expressing at least one neuroprotective agent. The compositions disclosed comprise hematopoietic stem progenitor cells transduced to express a neuroprotective agent.

Claims (19)

1 . A short hairpin RNA molecule (shRNA) that targets a Nox2 polynucleotide, the shRNA comprising the following sequence (SEQ ID NO: 1):

                             ▾

5′ C    CCUCCU         A                       -

    CUGG      GCA-GUGCC CGCUNNNNNNNNNNNNNNNNNNN-

                                               -     

    GACC      CGU CACGG GUGANNNNNNNNNNNNNNNNNNN-

3′UC    ---AUU   A     C                       -

     CAU

NNCUC   G

         U

NNGAG   G

     AUG.

2 . The shRNA of claim 1 , further comprising 5′ and 3′ flanking sequences derived from miR223.

3 . A method of reducing a pro-inflammatory response in a cell, the method comprising contacting the cell with an shRNA targeting Nox2 of claim 1 , thereby reducing pro-inflammatory response.

4 . The method of claim 3 , wherein the cell is further contacted with a metallothionein or a polynucleotide encoding the metallothionein.

5 . The method of claim 3 , wherein the method reduces expression of one or more polypeptides selected from the group consisting of Iba1, Nox2, Arg-1, Mrc-1, Tnfa, IL-1b, Il-6 and Il-10, and/or Bach1, Carhsp1, Cebpb, Csf1r, Inpp5d (Ship-1), Pea15a Olfml3 and Sall1, and Tnf alpha or a polynucleotide encoding the polypeptide.

6 . A method of treating a subject having or having a propensity to develop amyotrophic lateral sclerosis (ALS), the method comprising administering to the subject an effective amount of a composition comprising a cell comprising an shNox2 of claim 1 , thereby treating ALS.

7 . The method of claim 6 , wherein the cell is hemizygous for the CX3CR1 gene.

8 . The method of claim 6 , wherein the method reduces expression of one or more polypeptides selected from the group consisting of Iba1, Nox2, Arg-1, Mrc-1, Tnfa, IL-1b, Il-6 and Il-10 and/or Bach1, Carhsp1, Cebpb, Csf1r, Inpp5d (Ship-1), Pea15a Olfml3 and Sall1, and Tnf alpha or a polynucleotide encoding said polypeptide.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 26, 2026
From: BIFFI, ALESSANDRA
To: THE CHILDREN'S MEDICAL CENTER CORPORATION; DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 073911/0707 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 26, 2026
From: MOLINA-ESTEVEZ, FRANCISCO J.
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 073911/0724 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 26, 2026
From: PEVIANI, MARCO
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 073911/0768 →
Continuity (3)
Continuation PCTUS2020053826 · Oct 1, 2020
Provisional Application 62908942 · Oct 1, 2019
Related Publication 20220290157A1 · Sep 15, 2022
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