Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration

Abstract

Duchenne Muscular Dystrophy (DMD) is a progressive and fatal muscle-wasting disease with no known cure. We previously reported the preliminary safety and efficacy up to six months after the administration of DT-DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of myoblasts of DMD patient and the normal donor. In this 12-month follow-up study, we report on the safety and functional outcomes of three DMD patients after the systemic intraosseous administration of DT-DEC01. The safety of DT-DEC01 was confirmed by the absence of Adverse Events (AE) and Severe Adverse Events (SAE) up to 21 months after intraosseous DT-DEC01 administration. The lack of presence of anti-HLA antibodies and Donors Specific Antibodies (DSA) further confirmed DT-DEC01 therapy safety. Functional assessments in ambulatory patients revealed improvements in 6-Minute Walk Test (6MWT) and timed functions of North Star Ambulatory Assessment (NSAA). Additionally, improvements in PUL2.0 test and grip strength correlated with increased Motor Unit Potentials (MUP) duration recorded by Electromyography (EMG) in both ambulatory and non-ambulatory patients. DT-DEC01 systemic effect was confirmed by improved cardiac and pulmonary parameters and daily activity recordings. This follow-up study confirmed the safety and preliminary efficacy of DT-DEC01 therapy in DMD-affected patients up to 12 months after intraosseous administration. DT-DEC01 introduces a novel concept of personalized myoblast-based cellular therapy that is irrespective of the mutation type, does not require immunosuppression or the use of viral vectors, and carries no risk of off target mutations. This establishes DT-DEC01 as a promising and universally effective treatment option for all DMD patients. Graphical Abstract

Efficacy of Engraftment and Safety of Human Umbilical Di-Chimeric Cell (HUDC) Therapy after Systemic Intraosseous Administration in an Experimental Model

“…Based on these encouraging outcomes on safety and efficacy tested in the preclinical mdx/scid mouse model of DMD, we have tested DEC cell therapy in the first-in-human study in DMD patients. Specifically, we have confirmed both the safety and efficacy of DEC chimeric myoblasts in DMD patients up to 12 months [71,72] and currently up to 24 months after systemic intraosseous administration to DMD patients without the need for immunosuppression. These promising outcomes underscore the feasibility of scaling up chimeric cell propagation under the good manufacturing practice (GMP) conditions, as confirmed in our pilot clinical study [71,72].…”

Chimeric Cell Therapies as a Novel Approach for Duchenne Muscular Dystrophy (DMD) and Muscle Regeneration

“…The most essential quality of DEC therapy is that DEC cell creation does not require cellular reprogramming, genome-editing, or viral vector-induced engineering, and has proven to be safe. Consequently, these encouraging results of the preclinical phase of DEC therapy development support the first in-human study [98][99][100].…”

“…The primary goal of the first in-human study, initiated in 2021, was to assess the safety and efficacy of a single dose of DT-DEC01 therapy, administered to 6-15 years old boys with genetically confirmed DMD. The study was designed as a single-site, open-label pilot study for the enrollment of ten DMD patients, regardless of the gene mutation and the ambulatory status [98][99][100]. Study participants received a single dose of (2 × 10 6 /kg body weight) DT-DEC01 cells via direct intraosseous administration to the bone marrow cavity of the iliac crests.…”

“…Study participants received a single dose of (2 × 10 6 /kg body weight) DT-DEC01 cells via direct intraosseous administration to the bone marrow cavity of the iliac crests. Following administration, the participants were subjected to a 6-month active follow-up period, and 18 months of passive follow-up [98][99][100]. With this consideration, as the next step in the development of DEC cell technology for DMD and muscle regeneration, the systemic-intraosseous administration of human DEC cells derived from normal and DMD-affected donors following delivery to the mdx/scid mouse model of DMD was tested [92,93,96,97].…”

“…Study participants received a single dose of (2 × 10 6 /kg body weight) DT-DEC01 cells via direct intraosseous administration to the bone marrow cavity of the iliac crests. Following administration, the participants were subjected to a 6-month active follow-up period, and 18 months of passive follow-up [98][99][100].…”