Capricor’s Vesicle-based Therapy Holds Promise to Treat DMD, Preclinical Data Suggests

Capricor Therapeutics’ vesicle-based therapy CAP-2003, derived from the company’s proprietary cardiosphere-derived cells (CDCs), may be an effective therapy for Duchenne muscular dystrophy (DMD), according to preclinical data.

The company presented the results in August in two scientific posters at the 2018 Gordon Research Conference on Extracellular Vesicles in Newry, Maine.

Capricor’s lead candidate for the treatment of DMD is CAP-1002, which is composed of CDCs derived from the patient’s heart tissue. CDCs are a type of heart progenitor cells that can differentiate into mature heart cells and have been shown to have regenerative, immunomodulatory (regulation of the immune system), anti-inflammatory, and anti-scarring properties.

Capricor is recruiting patients for its randomized, double-blind, placebo-controlled Phase 2 study (NCT03406780), known as the HOPE-2 trial, that will evaluate the effectiveness of CAP-1002 in boys and young men with advanced DMD.

Results of a small Phase1/2 clinical trial, called HOPE Duchenne (NCT02485938), showed that a single administration of CAP-1002 directly into the heart improved heart muscle function as well as arm and hand strength, and reduced tissue scarring in people with DMD.

However, increasing evidence suggests that the therapeutic effects of CDCs are associated with their release of tiny extracellular vesicles called exosomes.

Exosomes are nano-sized, membrane-enclosed vesicles released by nearly every cell type in the body. They are filled with molecules that act as messengers to regulate several cellular processes, including immune and inflammatory responses, cell damage, and scarring.

These therapeutic properties, along with exosomes’ small size and ability to enter cells easily, make them strong potential therapeutic agents.

Thus, Capricor is evaluating CAP-2003 — CDC-derived extracellular vesicles — as a potential therapy for treating diseases associated with inflammation and scarring, including DMD.

In the first poster, titled “Extracellular Vesicles from Cardiosphere-Derived Cell and from Mesenchymal Stem Cells Show Different Immunomodulatory Capabilities and Distinct RNA Cargo,” the company shows the results of the comparison of the properties of CAP-2003 and extracellular vesicles derived from mesenchymal stem cells.

Mesenchymal stem cells have the potential to differentiate into cells that produce key factors that regulate immune responses, such as inflammation.

The results showed that CDC-derived extracellular vesicles (CAP-2003) are significantly bigger than mesenchymal stem cell-derived vesicles and contain a unique cocktail of molecules.

CAP-2003 also induced stronger anti-inflammatory and regenerative responses by rat and mouse macrophages — a type of white blood cell involved in removing cellular debris and in tissue repair — than mesenchymal stem cell-derived extracellular vesicles.

The researchers found that CAP-2003 was also able to regulate immune responses from T-cells, a type of white blood cell that is a critical component of the immune system.

These findings suggest that CAP-2003 may be a more effective therapeutic agent for the treatment of diseases associated with inflammation and scarring than mesenchymal stem cell-derived extracellular vesicles.

The second poster, “Efficacy and in vitro Uptake of EVs from Cardiosphere-Derived Cells,” focused on whether CAP-2003 recapitulates the therapeutic effects of CAP-1002 in a mouse model of DMD.

The results showed that CAP-2003 improves the exercise capacity of these mice to levels comparable to those achieved with CAP-1002.

“The studies … demonstrate that exosomes may be the active pharmaceutical ingredient (API) in CAP-1002, our cell therapy product, because these extracellular vesicles serve as cellular messengers, altering function and physiology to balance inflammation so that cellular repair can be facilitated,” Linda Marbán, PhD, Capricor’s chief executive officer, said in a press release.

The researchers also found that CAP-2003 is internalized more by immune cells, including macrophages, than by other type of cells, highlighting its immunomodulatory mechanism.

They noted that these data help to understand the mechanisms and target cells of CAP-2003, which will be crucial to identify which diseases might benefit from this therapy and the best delivery method.