What are the advantages of universal "chimeric cells" for DMD over gene therapy that prove long-term effectiveness?

October 8, 2022 eMedClub News/-September 26, 2022, Dystrogen Therapeutics announced that a clinical study of DT-DEC01, a research-based engineered cell therapy
for Duchenne muscular dystrophy (DMD), was achieved six months later in a clinical study under a hospital exemption agreement.

The findings were measured by the duration and amplitude of the motor potential on the electromyography (biomarker) compared to baseline, as well as the status of movement, including the motor function of three patients in the first low-dose cohort after 6 months of treatment and the safety
of the drug.

The three patients were 7-year-old ambulatory patients with exon 3-12 deletion, 15-year-old ambulatory patients with exon 48-50 deletion, and 6-year-old ambulatory patients with
senseless mutations.
Regardless of their genetic mutations, improvements in clinical and biomarkers were shown, embodied in improvements in grip strength as well as walking ability, during which no adverse events associated with DEC treatment (AEs and SAEs)
were observed.

DT-DEC01 is an engineered chimeric cell therapy made using Dystrogen's proprietary cell engineering technology to form chimeric cells by fusing healthy allogeneic myoblasts with myoblasts of DMD patients in vitro
.
This is a therapy based on malnourished protein-expressing chimeric cells (DECs), and obtaining healthy DMD genes from healthy donors produces full-length anti-amyotrophin, which has the ability to maintain the expression of
normal anti-amyotrophins.
DEC cells will increase the number of normal myoblasts and reduce inflammation and induce the replacement of fibrotic tissue, thereby significantly improving muscle strength and function in patients with DMD, which can prevent premature incapacitation of mobility and early death
in patients with DMD.

Notably, DEC cells express HLA features well and have multiple immunological advantages that minimize the immune response and the need for immunosuppression, as patients recognize DEC cells as "self" cells that evade attacks by the
immune system.
The therapy does not involve any genetic manipulation, so there is no risk of off-target mutations
.
Because viral vectors are not used, and their use does not depend on genetic mutations in DMD patients, DT-DEC01 is a universal therapy
for all DMD patients.

Preclinical studies have shown that DEC significantly expresses higher levels of CD56 and anti-amyotrophin compared with myoblasts in patients with DMD, closer to healthy myoblasts, and DT-DEC01 shows significant functional improvements
in cardiac, diaphragm, and other skeletal muscle strength and related functions.

▲ DT-DEC01 mechanism of action Source: the company's official website

Dr.
Kris Siemionow, MD, CEO of Dystrogen Therapeutics, said that at present, for boys and young people with DMD, there are no approved treatments that can cure or significantly alleviate the disease
.
DT-DEC01 engineered cell therapy has demonstrated consistent positive clinical and biomarker data in patients and can last for six months effectively, perhaps offering new hope
to patients.

Dystrogen Therapeutics, a clinical-stage life sciences company dedicated to the development of therapies for rare genetic diseases and disorders associated with aging, has developed a technology platform for cell engineering that has proven its effectiveness in preclinical trials, with several drugs still in the preclinical development phase
.

▲ Pipeline Image source: the company's official website

DMD and cell therapy

Globally, there is about one person with
DMD in every 3,600 men.
DMD is a rare X-chromosome recessive genetic disorder that causes a series of muscle diseases
due to mutations in the genes encoding anti-amyotrophin (Dystrophin) in the body, resulting in the deletion or functional defect of antiamyotroin.
Globally, the incidence of DMD is about 1 in 3500-1 in 5000 (newborns), and patients usually begin to develop at the age of 3-5 years, and often die
of respiratory failure at the ages of 20-30.
Currently, treatment options for patients with DMD are very limited
.

For diseases caused by this gene mutation, the current treatment methods focus on gene therapy and nucleic acid drugs, including the AAV gene therapy SRP-9001 (Sarepta) jointly developed by Sarepta and Roche, the intravenous AAV gene therapy PF-06939926 (Pfizer) developed by Pfizer, and the antisense oligonucleotide (ASO) therapy developed by Sarepta EXONDYS 51, VYONDYS 53, AMONDYS 45, SRP-5051, etc
.

In addition to the DT-DEC01 mentioned above, there is currently a cell therapy CAP-1002
in development.
CAP-1002 is an allogeneic cell therapy developed by Capricor for the treatment of advanced DMD, consisting of heart-derived cells (CDCs), a special cell population containing cardiac progenitor cells that improve muscle scarring or fibrosis and heart function
in DMD patients by releasing exosomes containing microRNA, noncoding RNAs and proteins.
In addition, CAP-1002 has also shown potent immunomodulatory activity, possibly promoting cell regeneration
.

Data from a Phase 2 clinical trial showed that CAP-1002 can reduce the loss of function of skeletal muscle function in the upper extremities by up to 70% while being safe
.
In July 2022, Capricor announced the completion of the first patient administration
of Phase 3 trials of CAP-1002.

At present, gene therapy is an important direction for DMD, can solve the potential genetic cause of DMD - anti-amyotrobin gene mutation, the gene therapy currently under research has also significantly improved the survival and exercise ability of patients in clinical trials, but gene therapy still has some unanswered questions, such as whether AAV therapy can be re-administered, whether it may cause side effects and whether it is suitable for all DMD patients
.

Gene therapy involves alteration of genetic material to treat genetic diseases; Cell therapy involves cell infusion and can provide therapeutic benefits
to patients.
This means that the two treatments can be used in combination, either individually to treat patients, as an alternative to patients who have failed gene therapy, or as complementary therapies to significantly improve the patient's condition
.

brief summary

At present, the two DMD cell therapies under development have entered the stage of clinical trials, and the experimental data show that the effectiveness of cell therapy for DMD can significantly improve the patient's limb function, enhance the ability to walk, and can achieve long-term effectiveness
.
In addition, gene therapy, which has successfully entered the late clinical stage after twists and turns, has also confirmed its effectiveness and safety in clinical trials
.
Whether as monotherapy or as a combination of two therapies with one of the two therapies as a complementary therapy, the development of these innovative drugs has brought new hope
to patients.

Resources:

1.
The official website of each company

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