Two rare diseases, two pieces of good news

Dr. Stephanie Cherqui

Last week saw a flurry of really encouraging reports from projects that CIRM has supported. We blogged about two of them last Wednesday, but here’s another two programs showing promising results.

UC San Diego researcher Dr. Stephanie Cherqui is running a CIRM-funded clinical trial for cystinosis. This is a condition where patients lack the ability to clear an amino acid called cystine from their cells. As the cystine builds up it can lead to multi-organ failure affecting the kidneys, eyes, thyroid, muscle, and pancreas.

Dr. Cherqui uses the patient’s own blood stem cells, that have been genetically corrected in the lab to remove the defective gene that causes the problem. It’s hoped these new cells will help reduce the cystine buildup.

The data presented at the annual meeting of the American Society of Cell and Gene Therapy (ASCGT) focused on the first patient treated with this approach. Six months after being treated the patient is showing positive trends in kidney function. His glomerular filtration rate (a measure of how well the kidneys are working) has risen from 38 (considered a sign of moderate to severe loss of kidney function) to 52 (mild loss of kidney function). In addition, he has not had to take the medication he previously needed to control the disorder, nor has he experienced any serious side effects from the therapy.

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Dr. Linda Marban of Capricor

Capricor Therapeutics also had some positive news about its therapy for people with Duchenne’s Muscular Dystrophy (DMD). This is a progressive genetic disorder that slowly destroys the muscles. It affects mostly boys. By their teens many are unable to walk, and most die of heart or lung failure in their 20’s. 

Capricor is using a therapy called CAP-1002, using cells derived from heart stem cells, in the HOPE-2 clinical trial.

In a news release Capricor said 12-month data from the trial showed improvements in heart function, lung function and upper body strength. In contrast, a placebo control group that didn’t get the CAP-1002 treatment saw their condition deteriorate.

Craig McDonald, M.D., the lead investigator on the study, says these results are really encouraging.  “I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function. This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited.”

You can read the story of Caleb Sizemore, one of the patients treated in the CIRM-funded portion of this trial.

Treatment for heart failure shows promising results for COVID-19 patients

Dr. Linda Marbán

To help with the coronavirus pandemic, many scientists are repurposing previously developed approaches or treatments to see if they can be used to treat patients with COVID-19. Capricor Therapeutics, lead by Dr. Linda Marbán, is using cardiosphere derived cells (CDCs), which are stem cells derived from heart tissue, to treat critically ill patients with COVID-19.

When a patient contracts the virus, their body produces cytokines, proteins that play an important role in the immune response. Unfortunately, having too many cytokines, known as a “cytokine storm”, leads to a severe immune reaction that can cause pneumonia, organ failure, and death. CDCs in previous studies have been shown to help regulate the immune response and cytokines, which could help patients with COVID-19.

Over the course of one month, six critically ill patients with COVID-19, five of whom were on mechanical ventilators, were treated with CDCs. In these compassionate care cases, five male patients and one female patient received treatment. Of the five patients on ventilator support, four patients no longer required ventilator support within just one to four days after treatment. Although these results are promising, it is important to remember that this treatment is in very early testing and will need to demonstrate significant improvement in larger patient groups.

Following a review of the results of this small study, the U.S. Food and Drug Administration (FDA) approved treatment of up to an 20 additional COVID-19 patients.

In a press release, Dr. Marbán discuses the results of the compassionate care study and treatment of additional COVID-19 patients.

“As the global medical community continues to come together in its battle against COVID-19, the results of our initial compassionate care cases are extremely promising and what we had anticipated. We look forward to continuing to treat additional patients under our recently approved expanded access program Investigational New Drug application.” 

The treatment used was developed with the help of a CIRM funded preclinical study. It has also been used in three CIRM funded clinical trials for heart disease associated with duchenne muscular dystrophy, heart failure, and pulmonary arterial hypertension.

Encouraging Progress for Two CIRM Supported Clinical Trials

This past Wednesday was Stem Cell Awareness Day, a day that is meant to remind us all of the importance of stem cell research and the potential it has to treat a wide variety of diseases. On this day, we also released an independent Economic Impact Report that showed how $10.7 Billion (yes, you read that right) was generated as a direct result of the the legacy we have built as a state agency that funds groundbreaking research.

Aside from the monetary incentive, which is an added bonus, the research we fund has made encouraging progress in the scientific field and has demonstrated the positive impact it can have on various disease areas. This week, two clinical trials supported by CIRM funding have released very promising updates.

Duchenne Muscular Dystrophy

Capricor Therapeutics, Inc. has presented positive results for a clinical trial related to a treatment for duchenne muscular dystrophy (DMD), a genetic disorder. DMD leads to progressive muscle degeneration and weakness due to its effect on a protein called dystrophin, which helps keep muscle cells intact.

The treatment that Capricor is testing is called CAP-1002 and consists of a unique population of cells that contain cardiac progenitor cells, a type of stem cell, that help encourage the regeneration of cells. CIRM funded an earlier clinical trial for this treatment.

The early results of this current trial describe how teens and young men in the advanced stages of DMD saw improvements in skeletal, lung, and heart measurements after receiving multiple doses of the treatment.

In a news release, Dr. Linda Marban, Chief Executive Officer of Capricor, expresses optimism for this clinical trial by saying,

“We are very pleased that the interim analysis from this double-blind placebo-controlled study, has demonstrated meaningful improvements across three clinically relevant endpoints in older patients with limited remaining treatment options.”

In the same news release, Dr. Craig McDonald, the national principal investigator for the trial, echoes the same sentiment by stating,

“The results from this trial to date are very promising in that the cells appear to positively impact skeletal, pulmonary and cardiac assessments in older DMD patients who have few, if any, remaining treatment options. We are eager to meet with the FDA to discuss the next steps for this promising program.”

Mantle Cell Lymphoma

Additionally, Oncternal Therapeutics has decided, because of positive results, to open an expansion of its CIRM-funded clinical trial aimed at treating patients with mantle cell lymphoma (MCL). The treatment involves an antibody called cirmtuzumab, named after us, in combination with a drug called ibrutinib.

The preliminary results were from the first six patients with MCL that were treated in the trial. One patient with MCL, who had relapsed following an allogeneic stem cell transplant, experienced a confirmed complete response (CR) after three months of cirmtuzumab plus ibrutinib treatment. This complete response appears to be sustained and has been confirmed to be ongoing after completing 12 months of the combination treatment. A second confirmed complete response occurred in a patient who had progressive disease after failing several different chemotherapy regimens, bone marrow transplant and CAR-T therapy. 

In a news release, Dr. Hun Lee, an investigator in the trial, states that,

“It is encouraging to see that the drug has been well tolerated as well as the early signal of efficacy of cirmtuzumab with ibrutinib in MCL, particularly the rapid and durable complete responses of the heavily pre-treated patients after three months of therapy, which is an unusually fast response in this patient population.”