Treating Degenerative Diseases with Cell-Regenerating Exosomes

In this interview, Life Extension® talks to Dr. Linda Marban, CEO of Capricor Therapeutics.

Capricor Therapeutics is a biotechnology company focused on the discovery of cell therapies for the treatment of various diseases.

One of Capricor’s areas of expertise is using specialized cells derived from the heart (cardiosphere-derived cells) to deliver regenerative factors known as exosomes.

Capricor is currently investigating the effects of their heart-derived cells, known as CAP-1002, to speed recovery for COVID-19 patients and restore muscle function in the fatal disease of Duchenne muscular dystrophy.

Dr. Marban discusses some of the company’s current research and its potential to improve healthy longevity in aging people.

LE: What are cardiosphere-derived cells, also known as CAP-1002?

Dr. Marban: Our cells function as a delivery system, delivering their exosomes which help to reprogram existing cells in the body to make new proteins and reduce inflammatory consequences of diseases (which is at the root of nearly every disease). The cells that Capricor discovered are derived from the heart and possess unique properties. By isolating out these cells that help protect the heart, we are able to multiply and divide these cells and then deliver their messages of healing through the exosomes in a larger dose—essentially, taking advantage of these natural processes and expanding upon them for clinical utility.

LE: Can you describe the harvesting process and application of CAP-1002?

Dr. Marban: We take hearts that would typically be used for transplantation (and are not able to be used as such, for technical reasons) and take them back to our labs where we perform a proprietary process that includes isolating the cells, which we then put into our expansion protocol so we can have enough for dosing. We can get up to thousands of doses using large-scale manufacturing methods from a single heart using this technique and have no supply-chain issues.

LE: CAP-1002 has demonstrated favorable modulation of various inflammatory cytokines and regulation of the immune response. What diseases and other conditions can be treated by these unique cells?

Dr. Marban: There are many diseases that can be treated this way. At Capricor, we are focusing on rare diseases such as Duchenne muscular dystrophy and we focused on treating diseases of inflammation, which includes exploring the use of CAP-1002 for the treatment of COVID-19 patients.

LE: Tell us about your work using CAP-1002 on COVID-19? There is a rush to understand, treat and prevent this global pandemic. Why might CAP-1002 be beneficial?

Dr. Marban: The most important part of the cells is the immunomodulatory capability. Multiple, published, peer-reviewed studies of our cells have demonstrated favorable modulation of various inflammatory cytokines and regulation of the immune response. The current understanding of COVID-19’s later stages are thought to be due to overstimulation of the immune system, which triggers a cytokine storm in which the body is overwhelmed with pro-inflammatory molecules. This immune response may become excessive and pathologic, inducing pneumonia, organ failure and death. Therefore, it can be the body’s overreaction to COVID-19, rather than the virus itself, that delivers the fatal blow.

We started a small effort during the beginning of the pandemic where we treated patients with a compassionate use protocol to see if there was any potential impact on outcomes. What we found was extremely promising. Four of our patients fully recovered and are now back home contributing to and living a full life again. We are continuing our probe into the impact of CAP-1002 to treat COVID-19 by starting a randomized, controlled clinical trial which we will be working on imminently, subject to FDA approval.

LE: CAP-1002, which are allogenic (genetically dissimilar) cardiosphere-derived cells, stimulate the immune system for cellular regeneration and are currently in clinical trials. What are your findings?

Dr. Marban: The most important finding we’ve made is in our Duchenne muscular dystrophy (or DMD) clinical trials. CAP-1002 is a cell that has shown to have profound immunological capabilities and leads to cellular repair. It is not functioning as a stem cell in this context. However, it triggers other cells to re-enter the cell cycle and repair damaged muscle. In DMD, the patients who have this disease do not have the gene to make a protein called dystrophin. Dystrophin is the largest protein in the body, it provides structure to cells and protects them from damage on a day-to-day basis. The most notable that are affected by this are the muscle cells. DMD is a chronic, progressive disease where boys and young men typically start showing symptoms of it around age three and their lifespan is typically limited to their 20s.

CAP-1002 has been shown to improve muscle strength and increase the ability of patients to improve movements in their arms, shoulders, and hands. These are patients who are in wheelchairs already, so they will now have better function of the muscles in their upper limbs. This will help them to drive their wheelchair, use their smartphone, and improve their quality of life in many ways.

We have also seen positive data in cardiac endpoints such as ejection fraction and volumes, which is extremely encouraging.

We are now asking the FDA to consider some type of accelerated approval for this product following its incredibly positive Phase-II data from our latest clinical trial.

LE: Can you please explain to our readers what exosome-based therapeutics are?

Dr. Marban: Exosomes are an extremely exciting and emerging class of therapeutic being explored for the treatment of a variety of different diseases. They are extremely small, single-membrane, secreted vesicles that are enriched in selected proteins, lipids, and nucleic acids. They are secreted by nearly all cell types and they are how cells communicate with each other. In other words, exosomes are the “messengers” of cells—they play a distinct role in the transmission of molecules to other cells. At Capricor, we are harnessing the power of intercellular communication and engineering exosomes into therapeutics by loading them with custom-designed nucleic acids or proteins that can direct cellular behavior and ultimately change biology.

LE: How may these nanosized particles be used to treat various diseases?

Dr. Marban: Exosomes can be used for a whole host of different diseases and biologic applications. For example, we are now developing a potential vaccine therapy using exosomes for COVID-19. From this foundation, they can be used for other types of vaccines such as other infectious diseases or even as an immunotherapy for cancer, through targeting and killing malignant cells before they have a chance to expand and metastasize. Exosomes also can be used for genetic diseases. You can also do an array of protein replacement therapies. Essentially, anything that you want to load inside of a cell, which we’ve been having trouble as a field doing, can be imagined using an exosome to accomplish this, i.e. replace proteins inside cells.

LE: We are aware of your HOPE Trial and the use of cardiosphere-derived cells (CAP-1002) to treat Duchenne Muscular Dystrophy, which is nearly always fatal. We commend you for it. Projecting ahead, do you see Capricor’s innovations changing medicine by treating degenerative diseases like heart failure and bone marrow disorders?

Dr. Marban: Capricor’s foundational work is based on the premise of using a cell derived from cardiac tissue to treat heart disease. In fact, we have published and shown very promising data in advanced heart failure with the use of our cells. For the last few years, we have stayed focused on rare cardiac diseases such as Duchenne muscular dystrophy, but we remain open to exploring the use of our technology in other cardiac diseases.

LE: Is Capricor as optimistic as Life Extension® is about the potential of CAP-1002 to favorably impact human longevity? If so, in what ways will these unique cells promote human longevity?

Dr. Marban: One of the students in our lab did an interesting study a few years ago where she studied the increased longevity in rats treated with the cells. Through her research, she successfully demonstrated transfusion of blood from one of the treated rats into a rat that was untreated. We believe our cells have the potential of longevity of animals, but we have not yet tested this in humans. However, if you can successfully cut down the rate of heart disease and other diseases that have an effect on the human lifespan, you are indirectly addressing increasing longevity, as well.

LE: In animal studies cardiosphere-derived cells have restored certain markers of aging such as youthful gene expression, longer telomeres, increased exercise capacity and reduced inflammatory markers—all good signs to reduce the burden of aging. How soon might this be translated into human studies to reverse certain aging processes?

Dr. Marban: This is always the hard part of being a smaller biotech company. The kinds of studies that would deduce this would be large, long, and expensive. At this time, we are not using our cells for the treatment of aging, but we remain focused on treating diseases of inflammation which are indirectly related to the aging process.

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