Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.


Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of March 2022.


Prof. Aartsma-Rus reads and comments on the paper titled: Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Today’s pick by Amizadeh et al on the HOPE-2 trial by Capricor Therapeutics published in The Lancet, Doi 10.1016/S0140-6736(22)00012-5.

Most Duchenne patients are non ambulant. However, most clinical trials are done in ambulant patients. This trial is different: conducted in late ambulatory and non ambulatory patients. Most stem cell treatments aim to restore dystrophin, this trial is different again:

The injected cells are cardiosphere-derived cells (CDCs). These cells excrete factors that improve regeneration, reduce fibrosis and change the immune response from a negative to a more benign response. CDCs do not have eternal life: treatment is needed every 3 months.

Studies in mdx mice showed improved function & survival (beyond 2 years – very long term preclinical study!) In a previous trial CDCs were injected into the coronary artery of the heart as a single treatment, which was safe and well tolerated. Here intravenous injection was used.

The trial was a double blind placebo controlled trial in 20 Duchenne patients, 12 in the placebo group and 8 in the treated group. Patients were treated every 3 months. One patient in the CDC treatment group dropped out due to a hypersensitivity reaction after the first infusion.

3 placebo treated patients dropped out of the trial. For 10 placebo patients and for 8 treated patients baseline and 12 month follow up data were available. For the performance upper limb (PUL) test the treated patients showed a slower decline than the placebo group.

In total patients received 69 infusions, which generally was well tolerated. 5 hypersensitivity reactions were observed, including 1 allergic reaction requiring hospitalization & epinephrine treatment. Afterwards patients received pretreatment with steroids and anti-allergens

Heart function was monitored as well. Treated patients had a stable ejection fraction, while there was a decrease in the placebo group. No effect was seen on pulmonary function. However, there is little decline in respiratory function so it is difficult to measure a slower decline.

Authors discuss that this is the first clinical trial showing treatment effects on the PUL. As the PUL was developed with Duchenne patients focusing on what they found important, these treatment effects likely reflect clinical benefit and a slower loss of independence of patients

Authors also discuss that the intravenous treatment appears to work and is of course much easier than the intracoronary treatment used earlier. Currently an open label extension study is ongoing and a phase 3 placebo controlled trial is planned.

Authors provide context on the other ongoing trials to restore dystrophin and approved therapies to restore dystrophin. I think the CDC treatment (if the phase 3 trials shows it is effective and safe) could be a nice add on treatment.

Authors discuss the limitations of the trial, i.e. a small group was treated so far and only for 12 months. So more work is needed. Looking forward to the phase 3 trial results. While phase 2 data are encouraging, more work is needed to confirm safety and efficacy.

I commend the authors and Capricor for the work and focusing on the upper limb function and patients who are (almost) non ambulatory.

Pictures by Annemieke, used with permission.

About Professor Annemieke Aartsma-Rus

Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).

Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.

In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.

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