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Development of CM-CS1 CAR Treg to Treat Amyotrophic Lateral Sclerosis (ALS)

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44NS132666-01
Agency Tracking Number: R44NS132666
Amount: $466,950.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: 105
Solicitation Number: PA22-176
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-19
Award End Date (Contract End Date): 2024-08-31
Small Business Information
Lebanon, NH 03766-1441
United States
DUNS: 828763263
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 320-8521
Business Contact
Phone: (617) 320-8521
Research Institution

Amyotrophic lateral sclerosis (ALS) patients develop fatal paralysis as a result of progressive motor neuron loss
in the brain and spinal cord. There are more than 5,000 new cases of ALS per year in the United States, with
typical age of onset between 40 and 70 years of age. While SOD1 is a cytoplasmic protein, misfolded SOD1 can
be secreted and form extracellular oligomers and aggregates. Mutations in superoxide dismutase-1 (mSOD1)
result in misfolding and aggregation of SOD1 and are found in a subset of familial ALS cases. However,
misfolded SOD1 has also been identified in spinal cord samples from many sporadic cases of ALS. Regulatory
T cells (Tregs) have tolerogenic and anti-inflammatory functions and are being pursued as cell-based
therapeutics to block auto-inflammatory immune cells. Higher numbers of Tregs (CD4+CD25hiCD127lo) in ALS
patients are associated with a slower disease progression. We have developed novel chimeric antigen receptors
(CARs) that recognize aggregated SOD1 and trigger Treg function. In this manner, we aim to provide a large
number of Tregs that are specific for a disease-associated protein and will become activated at the site of
misfolded, aggregated SOD1. We have further enhanced the activity of CAR Tregs by engineering them to
produce BNDF, a key neuronal survival factor. We have developed a novel mouse model for ALS by breeding
the G93A SOD1 transgene onto the NSG mouse background to create mSOD1-NSG mice. These mice allow
the engraftment of human cells and they develop a progressive disease resulting in inflammation in the spinal
cord and limb paralysis that mimic findings in ALS. The aim of this project is to perform IND-enabling studies
required for translation of this therapy into the clinic.

* Information listed above is at the time of submission. *

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