Cell Therapy DT-DEC01 Continues to Show Efficacy in DMD Boys in Trial
All three showed signs of improvements irrespective of their DMD gene mutation
Dystrogen Therapeutics’ experimental cell therapy, DT-DEC01, continues to show signs of efficacy in three boys with Duchenne muscular dystrophy (DMD), who exhibited improved muscle strength and motor function after six months in a clinical trial.
All patients showed signs of clinical improvements irrespective of their mutation in the DMD gene.
These findings support DT-DEC01 as “a universal therapy for all DMD patients,” according to Dystrogen’s press release.
Improvements included an increase of up to 200% in the mean motor unit potential, a marker of muscle electrical activity, compared to the trial’s start (baseline) as assessed by electromyography, which records electrical activity of muscle tissue. Other markers of muscle function also improved in support of early trial data, including in a boy who had lost his ability to walk.
“There are currently no approved treatments for boys and young men with DMD that result in a cure or significant attenuation of the disease,” said Kris Siemionow, MD, PhD, CEO of Dystrogen. “It is very encouraging that we continue to see consistent positive clinical and biomarker data from our investigational DT-DEC01 engineered cell therapy, even at this low dose, and that the benefit of the therapy is sustained at 6 months.”
Duchenne is caused by mutations in the DMD gene, which lead to the loss of a protein critical for muscle health, called dystrophin. As a result, DMD patients experience progressive muscle weakness and wasting, leading to symptoms in multiple organs in the body.
Cell therapies are meant to regenerate damaged muscles by transplanting healthy muscle cell precursors from a donor. However, patients can develop an immune reaction against the donor cells, impairing their therapeutic efficacy. As a result, immunosuppressive treatments that curb these reactions are often applied but are associated with significant side effects.
DT-DEC01 may bypass the use of immunosuppressants and their side effects
Dystrogen’s experimental chimeric cell therapy, designed using the company’s proprietary cell engineering technology, may bypass these limitations. DT-DEC01 is based on the fusion of myoblasts — muscle cell precursors — from a healthy donor with those from a DMD patient.
The new cells, called dystrophin expressing chimeric (DEC) cells and generated in the lab, are transplanted into the patient’s bone marrow from which they are expected to reach skeletal and cardiac muscle. Once there, the cells “fuse” with resident myoblasts to form muscle fibers that are able to produce dystrophin. Since the cells retain the patient’s cell surface immune markers, the process avoids the risk of immune rejection.
By boosting dystrophin levels and preventing further muscle damage, DT-DEC01 is thought to help restore muscle function in all DMD patients, regardless of their underlying DMD gene mutation.
The clinical trial, ongoing in Poland, seeks to assess the safety, tolerability, and effectiveness of three increasing doses of DT-DEC01 in 10 boys, ages 5–18, with DMD.
Specifically, it aims to assess the cell therapy’s effects in functional motor abilities, motor skills, walking ability, upper limb function, muscle strength, and heart muscle health.
The study is being conducted under hospital exemption, a special access program that grants patients access to unapproved therapies under controlled setups for diseases of high unmet therapeutic need.
The new data is from a six-month follow-up of the first three patients, all with different DMD mutations, who received the lower dose of DT-DEC01 (2 million cells per kilogram).
Six-month data show DT-DEC01 led to improvements in three boys with DMD
Six months after treatment, a 7-year-old boy, who was still able to walk, showed improvements in muscle electrical activity (up to 108% since baseline), as assessed with electromyography. Motor function, evaluated with the North Star Ambulatory Assessment (NSAA), improved from a score of 31 to 34 (higher scores indicate better function). Other benefits were seen in walking ability — from 430 to 469 meters in the 6-minute walk test (6MWT), and by 14% in the 10-meter walk/run time.
The researchers also found the boy had greater grip strength (from 5 kg to 6.6 kg), higher scores in the Pediatric Outcomes Data Collection Instrument (PODCI) of functional outcomes (from 90 to 95), and a clinically significant increase in step count, measured by an activity tracker.
A 6-year-old boy, also able to walk, showed an increase of up to 124% in muscle electrical activity, along with better walking ability (from 339 to 390 meters in the 6MWT) and a greater NSAA score (26 to 28).
Other improvements were seen in his ability to stand after lying horizontally (supine to stand test), in his PODCI score (from 89 to 93), and in the Performance of the Upper Limb (PUL) score (32 to 39), among others. Increased step count was also reported.
Finally, a 15-year-old boy who was unable to walk showed greater muscle electrical activity (up to 287%), greater grip strength (8 kg to 9.7 kg) and greater PUL performance, along with increased step count.
No adverse events linked with the therapy have been reported.
These early clinical findings follow promising preclinical data where treatment with DEC cells led to long-term cellular and functional improvements in the heart, respiratory, and leg muscles of a mouse model of DMD.
“The improvements in functional and biomarker measures at 6 months in participants from the low dose cohorts who received DT-DEC01 are distinctly different from what an age-matched, natural history group would predict with DMD,” Siemionow said.
“When coupled with strong and sustained dystrophin expression in preclinical studies and encouraging clinical safety profile at 6 months, today’s results increase our confidence in DT-DEC01 and provide additional supportive evidence for this approach,” he added.