News Release

Thursday, November 14, 2019

Technique key to scale up manufacturing of therapies from induced pluripotent stem cells.

Researchers used artificial intelligence (AI) to evaluate stem cell-derived patches of retinal pigment epithelium (RPE) tissue for implanting into the eyes of patients with age-related macular degeneration (AMD), a leading cause of blindness.

The proof-of-principle study helps pave the way for AI-based quality control of therapeutic cells and tissues. The method was developed by researchers at the National Eye Institute (NEI) and the National Institute of Standards and Technology (NIST) and is described in a report appearing online today in the Journal of Clinical Investigation. NEI is part of the National Institutes of Health.

This AI-based method of validating stem cell-derived tissues is a significant improvement over conventional assays, which are low-yield, expensive, and require a trained user, said Kapil Bharti, Ph.D., a senior investigator in the NEI Ocular and Stem Cell Translational Research Section.

Our approach will help scale up manufacturing and will speed delivery of tissues to the clinic, added Bharti, who led the research along with Carl Simon Jr., Ph.D., and Peter Bajcsy, Ph.D., of NIST.

Cells of the RPE nourish the light-sensing photoreceptors in the eye and are among the first to die from geographic atrophy, commonly known as dry AMD. Photoreceptors die without the RPE, resulting in vision loss and blindness.

Bhartis team is working on a technique for making RPE replacement patches from AMD patients own cells. Patient blood cells are coaxed in the lab to become induced pluripotent stem cells (IPSCs), which can become any type of cell in the body. The IPS cells are then seeded onto a biodegradable scaffold where they are induced to differentiate into mature RPE. The scaffold-RPE patch is implanted in the back of the eye, behind the retina, to rescue photoreceptors and preserve vision.

The patch successfully preserved vision in an animal model, and a clinical trial is planned.

The researchers AI-based validation method employed deep neural networks, an AI technique that performs mathematical computations aimed at detecting patterns in unlabeled and unstructured data. The algorithm operated on images of the RPE obtained using quantitative bright-field absorbance microscopy. The networks were trained to identify visual indications of RPE maturation that correlated with positive RPE function.

Those single-cell visual characteristics were then fed into traditional machine-learning algorithms, which in turn helped the computers learn to detect discrete cell features crucial to the prediction of RPE tissue function.

The method was validated using stem cell-derived RPE from a healthy donor. Its effectiveness was then tested by comparing iPSC-RPE derived from healthy donors with iPSC-RPE from donors with oculocutaneous albinism disorder and with clinical-grade stem cell-derived RPE from donors with AMD.

In particular, the AI-based image analysis method accurately detected known markers of RPE maturity and function: transepithelial resistance, a measure of the junctions between neighboring RPE; and secretion of endothelial growth factors. The method also can match a particular iPSC-RPE tissue sample to other samples from the same donor, which helps confirm the identity of tissues during clinical-grade manufacturing.

Multiple AI-methods and advanced hardware allowed us to analyzeterabytesandterabytesof imaging data for each individual patient, and do it more accurately and much faster than in the past, Bajcsy said.

This work demonstrates how a garden variety microscope, if used carefully, can make a precise, reproducible measurement of tissue quality,Simon said.

The work was supported by the NEI Intramural Research Program and the Common Fund Therapeutics Challenge Award. The flow cytometry core, led by the National Heart, Lung and Blood Institute, also contributed to the research.

NEI leads the federal governments research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Schaub NJ, Hotaling NA, Manescu P, Padi S, Wan Q, Sharma R, George A, Chalfoun J, Simon M, Ouladi M, Simon CG, Bajcsy P, Bharti K. Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy. In-press preview published online November 14, 2019 in J. Clin. Investigation.

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NIST researchers use artificial intelligence for quality control of stem cell-derived tissues - National Institutes of Health

Chicago, IL, Nov. 14, 2019 (GLOBE NEWSWIRE) -- Dr. Keith Nemec the clinic director ofTotal Health Institute in Chicago has received yet another fellowship in his advanced research. Most recently Dr. Nemec received his fellowship in Stem Cell Therapy to add to his other fellowships in Regenerative Medicine and Integrative Cancer Therapies.

Dr. Nemec has overseen patient care for the last thirty-five years at Total Health Institute which is an alternative and integrative medical facility. Total Health Institute has seen over 10,000 patients who have traveled from around the world to seek Dr. Nemecs guidance in their healing journey.

Total Health Institute uses unique approach developed by Dr. Nemec called theSystems Sequence Approach to balance cellular communication between the cells, tissues, organs, glands and systems of the body. Dr. Nemec explains It is like knowing the combination to open the lock to complete healing. To open this lock, you must not only know the right systems to balance but also in the right sequence.

Dr. Keith Nemec is very excited about the research in stem cells and stem cell therapy that is why he focused his concentration in this area. According to Dr. Nemec All health and healing starts at the stem cell level. Whether a person has cancer, autoimmune disease or chronic diseases of aging they are all involving stem cells. In cancer, an inflammatory environment has mutated a normal stem cell into a cancer stem cell which is not killed with either chemotherapy nor radiation. This is why many times with conventional cancer treatment alone one tends to see improvements for a season but then return the cancer stem cell retaliates with a vengeance. Dr. Nemec also states Since all cells come from a base stem cell then the answer to all chronic disease can be found in activating the stem cells to produce an anti-inflammatory niche and continual healthy cell renewal.

Dr. Nemec is a member of the American Academy of Anti-Aging Medicine which is the largest and most prestigious group of Regenerative and Anti-Aging Medicine doctors in the world. He received his masters degree in Nutritional Medicine from Morsani College of Medicine. He has also published 5 books including: The Perfect Diet, The Environment of Health and Disease, Seven Basic Steps to Total Health and Total Health = Wholeness. Dr. Nemec has also published numerous health articles including: The Single Unifying Cause of All Disease and The answer to cancer is found in the stem cell and for 18 years he hosted the radio show Your Total Health in Chicago AM1160.

Total Health Institute boasts all 5 starreviews on RateMDs, an A+ rating onBBBand is top rated on Manta.

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Leading Alternative Healing Director of Total Health Institute Reviews and Receives 3rd Fellowship in Stem Cell Therapy - GlobeNewswire

By Justin A. Varholick, Ph.D.

As we grow older theres an impending fear that we will slowly, but surely, begin to lose our vision. This slow loss of vision is clinically dubbed low vision and impacts more than 39 million Americans, costs $68 billion annually in direct health care costs, and is only growing in our population as baby boomers enter the at-risk age of 65 and older. Magnifiers can often be used to help people with acute issues of low vision, but are often inconvenient and frustrating. More serious issues of low vision such as cataracts, age-related macular degeneration, glaucoma, and diabetic retinopathy require advanced treatment and surgery. For example, cataracts can be improved or reversed by removing the cloudy lens and replacing it with an artificial one. Such surgeries are not always ideal, or convenient, and further contribute to the already hefty direct health care costs. But, a recent breakthrough by Japanese scientists, in correcting blurry vision, might reverse this bleak future.

Old cells can become new againOur story begins around the mid-20th century, in 1958. A young and aspiring scientist, named John Gurdon, was studying frogs at the University of Oxford in England. Not everyone thought Gurdon would end up actually becoming a scientist. In his early days his school master thought such a career was far-fetched for Gurdon. Indeed, he ranked last in his Biology class out of 250 students. Yet despite such poor grades, Gurdon found himself studying frogs at Oxford and earning a doctoral degree in Biology. And his studies would surprisingly lead to a breakthrough in vision, and likely many other issues in human health, like Parkinsons Disease, heart disease, and spinal cord injury.

At the time Gurdon was trying to test an age-old theory on cell development. Many scientists before him discovered that cells the smallest unit of life begin without a clear fate in the early stages of an embryo. Then as the cell develops, their fate becomes more clear. They become cells of the heart, of the brain, the kidneys, the stomach, the spinal cord, or the eyes. But they cannot go back to a time when they had no fate, or specialization. The cells can only develop in one direction, from no destiny, to a clear path, then to a mature adult cell; like one found in the heart. But you just cant take a heart cell and start the process over, maybe turning it into a brain cell.

In disagreement with this theory, Gurdon did a simple experiment. He knew that a tadpole has more adult cells than a frog egg. A tadpole has gills, a heart, eyes, etc., while a frog egg simply does not. So, he cut open the tadpole and removed a single cell from the intestine; an intestinal cell. He then cut open the intestinal cell and removed its nucleus; the seed of the cell carrying all the DNA. Very carefully, he did the same with the frog egg, and finally replaced the nucleus of the frog egg with the nucleus of the intestinal cell. According to the age-old theory, the intestinal nucleus should stop normal development of the frog egg. But thats not what happened.

Instead, the new frog egg continued to develop normally, becoming a tadpole that later became an adult frog. Gurdon thought this was unbelievably odd, and so did everyone else in science. After many more experiments doing the exact same procedure (i.e., replication), it seemed that what he saw was a real, replicable fact. For some reason the nucleus of the intestinal cell was able to reverse itself to have no fate and slowly develop into any other adult cell. The seed from the intestine somehow could become the seed of a heart, brain, kidney, or even an eye cell and of course, an intestinal cell too.

After many more experiments testing the same theory, on many more animals, it seemed the theory was true, but it just didnt work for mammals. Given that the same effect could not be repeated in a mammal, some believed this discovery did not apply to humans. But they were wrong.

The discovery of induced pluripotent stem cellsAlmost 45 years later, around the start of the millennium, Shinya Yamanaka and Kazutoshi Takahashi began running experiments that would translate Gurdons findings to humans. Born after Gurdons findings were already published and well known, Yamanaka and Takahashi grew up in a world in which the fact that old cells can become new again was widely knowna solid foundation for further hypotheses, experiments, and discovery. So, the scientists set out to do what no one had before: turn adult skin cells of mice into new cells without a clear fate.

Yamanaka, the lead investigator of the study, shared a similar early history with Gurdon. He first became a medical doctor in Japan but was frustrated by his inability to quickly remove small human tumors taking over an hour rather than the typical 10 minutes. Senior doctors gave him the nickname Jamanaka, a Japanese pun for the word jama meaning obstacle. He then found himself earning a PhD in pharmacology and becoming a post-doctoral scientist, but spent more time caring for mice than doing actual research. Frustrated again, his wife suggested he just become a practicing physician. Despite her advice, Yamanaka applied to become an Assistant Professor at Nara Institute of Science and Technology, in Japan, and won everyone over with his fantastical ideas of investigating embryonic stem cells; the cells without a clear fate.

Then the persistence paid off when Yamanaka with his assistant, Takahashi discovered how to induce adult skin cells from mice to return to an embryonic, or stem cell, state without a clear fate. They began their experiments knowing that gene transcription factors proteins that turn genes on and off were responsible for keeping embryonic cells in a state without a clear fate. They thought that by turning specific genes on and off with these factors, they could turn back time and make an adult cell embryonic again. So, they tried many different combinations of gene transcription factors and ultimately discovered that 4 specific ones were enough to induce an adult skin cell to a mouse to become an embryonic cell. Because these re-newed embryonic cells, or stem cells, originally came from adult cells they came up with a new name, induced pluripotent stem cell. Broken down, induced pluripotent stem cells means that the cell was induced to become pluripotent pluri meaning several, like plural, and potent meaning very powerful (and stem meaning to have the ability to turn into any cell in the body).

These induced pluripotent cells were thought to be very powerful indeed and scientists across the globe were excited by this great discovery. They had visions of taking a persons skin or blood, forming them into induced pluripotent cells, and then using them to grow a new liver or new parts of the brain. Laboratories across the world confirmed the results by repeating the experiment.

Human stem cells Just repeating the experiments in mice, or frogs, was not enough. They needed to begin making induced pluripotent stem cells from humans. Enter scientists from the University of Wisconsin-Madison. The lead scientist, James Thomson was already well known for deriving primate embryonic cells from rhesus monkeys in 1995 and the first human embryonic cell line in 1998. In fact, Thomsons accomplishment of isolating embryonic cells from monkeys was the first sound evidence that it was possible to do the same for humans. Such discoveries placed him on the forefront in ethical considerations for research using human embryos and the most obvious scientist to lead the path toward making induced pluripotent stem cells from humans.

Thomsons team made the first human derived induced pluripotent stem cells from adult skin, with Yamanaka as a co-scientist. They followed the same general principles set by Yamanaka, who did the procedure with mouse skin cells. Importantly to Thomson, this discovery helped to relieve some ethical controversy with using human embryos to make human stem cells. By being able to induce adult human skin to become pluripotent stem cells, much research on human stem cells could be done without human embryos albeit research with human embryos remains necessary.

Yet more important to the discussion at hand, the ability to induce human skin to become pluripotent stem cells placed us on the edge of a breakthrough. With some clinical trials in humans, the fantasy of growing a new liver, heart, or eye was more a reality than ever before.

The start of human trials In 2012, around the time both Gurdon and Yamanaka were presented with the Nobel Prize in Physiology and Medicine for their work leading to induced pluripotent stem cells, human clinical trials were beginning in Japan. The first clinical trial was for age-related macular degeneration, an eye condition leading to blindness. Unfortunately, this trial was quickly terminated when Yamanaka and his team identified small gene mutations in the transplanted induced pluripotent stem cells from the first patient. Although the procedure did cure the patient of macular degeneration, these small gene mutations worried the scientists because they could lead to tumor development.

But recently with the introduction of an inducible suicide gene that can signal cells with abnormal growth to die, human trials are starting up again. In October of 2018, Japanese scientists began trials with Parkinsons disease, a brain disease related to a shortage of neurons producing dopamine. Scientists took cells from the patients, made them into induced pluripotent stem cells, guided them to develop into dopamine producing cells, and then deposited them in the dopamine centers of the brain through surgery. The outcome is promising since similar procedures in monkeys have been successful.

Other trials in Japan have also started, including spinal cord injury and one for replacing the cornea of the eye. Early results replacing damaged corneas with induced pluripotent stem cells, thereby correcting blurry vision, were just announced at the end of August. Although it will take more patients and safety checks before all humans can get induced pluripotent cells to correct their damaged eyes, malfunctioning brains, or broken spinal cords, Takahashi the post-doctoral scientist working with Yamanaka thinks it might happen as early as 2023. So, it looks like that in our lifetime we just might be able to stay young and enjoy retirement because of great breakthroughs in animal research.Note, EuroStemCell is a great resource for learning more about the ethics and research currently being done with stem cells derived from human embryos.

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BREAKTHROUGH: Her vision was getting worse, then animal research made things clear - Speaking of Research

NESS ZIONA, Israel, Nov. 11, 2019 /PRNewswire/ --Kadimastem Ltd.(TASE: KDST),a clinical stage cell therapy company, today announced that it will present the interim results of Cohort A of its ongoing Phase 1/2a Clinical Trial in ALS (as published in Company's press release) at the 7th International Stem Cell Meeting, to be held on November 12-13 at the Dan Panorama Hotel in Tel Aviv, Israel.

The International Stem Cell Meeting, hosted by the Israel Stem Cell Society, is a highly reputed conference, participated by international world leaders in stem cell research.

Presentation Details:

Title: "FIRST IN HUMAN CLINICAL TRIALS WITH HUMAN ASTROCYTES AS A NOVEL CELL THERAPY FOR THE TREATMENT OF ALS"

Session:ONGOING CLINICAL TRIALS WITH CELL THERAPY

Presenter:Arik Hasson, PhD, Executive VP, Research and Development, Kadimastem

Date:Wednesday, November 13, 2019

Time:1:50 pm Israel

Location: Dan Panorama Hotel, Tel Aviv, Israel

Rami Epstein, CEO of Kadimastem, stated: "We are pleased to share these results with global leaders in the cell therapy and stem cells industry,demonstrating the potential of AstroRx, our astrocyte-based cell therapy product,to bring treatment to ALS patients, and possibly other neurodegenerative diseases. We look forward to further share data of this ongoing trial, with final results of cohort A expected by year-end 2019and results of cohort B expected in Q3, 2020."

About the Phase 1/2a ALS Clinical Trial

The Phase 1/2a trial is an open label, dose escalating clinical study to evaluate the safety, tolerability and preliminary efficacy of AstroRxcells in patients with ALS. The trial is expected to include 21 patients and is being conducted at the Hadassah Medical Center, Jerusalem, Israel. The primary endpoints of the trial are safety evaluation and tolerability of a single administration of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), administered in escalating low, medium and high doses (100x106, 250x106, and 500x106 cells, respectively). The medium dose will also be administered in 2 consecutive injections separated by an interval of ~60 days. Secondary end points include efficacy evaluation and measurements. Treatment is administered in addition to the appropriate standard-of-care.

About AstroRx

AstroRx is a clinical grade cell therapy product developed and manufactured by Kadimastem in its GMP-compliant facility, containing functional healthy astrocytes (nervous system support cells) derived from human Embryonic Stem Cells (hESC) that aim to protect diseased motor neurons through several mechanisms of action. The Company's technology enables the injection of AstroRxcells into the spinal cord fluid of patients suffering from Amyotrophic Lateral Sclerosis (ALS) with the goal of supporting the malfunctioning cells in the brain and spinal cord, in order to slow the progression of the disease and improve patients' quality of life and life expectancy. AstroRxhas been shown to be safe and effective in preclinical studies. AstroRxhas been granted orphan drug designation by the FDA.

About ALS

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease causing disfunction in the upper and lower motor nerves that control muscle function. ALS leads to muscle weakness, loss of motor function, paralysis, breathing problems, and eventually death. The average life expectancy of ALS patients is 2-5 years. According to the ALS Therapy Development Institute, it is estimated that there are approximately 450,000 ALS patients worldwide of which 30,000 reside in the US. According to the ALS Foundation for Life, the annual average healthcare costs of an ALS patient in the US are estimated at US$ 200,000. Thus, the annual healthcare costs of ALS patients in the US alone amount to US$ 6 Billion.

About Kadimastem

Kadimastem is a clinical stage cell therapy company, developing and manufacturing "off-the-shelf" allogeneic proprietary cell products based on its platform technology for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into clinical grade functional cells. AstroRx, the Company's lead program, is a clinical-grade astrocyte cell therapy for the treatment of ALS, currently undergoing a Phase 1/2a clinical trial. In addition, preclinical trials are ongoing with the Company's IsletRx pancreatic functional islet cells for the treatment of insulin dependent diabetes. Kadimastem was founded by Prof. Michel Revel, CSO of the Companyand Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Prof. Revel received the Israel Prize for the invention and development of Rebif, a multiple sclerosis blockbuster drug sold worldwide. Kadimastem is traded on the Tel Aviv Stock Exchange (TASE: KDST).

Company Contacts:Yossi Nizhar, CFO y.nizhar@kadimastem.com+972-73-797-1613

Investor and Media Contact:Meirav Gomeh-Bauermeirav@bauerg.com+972-54-476-4979

Global Media Contact:Dasy (Hadas) MandelDirector of Business Development, Kadimastemd.mandel@kadimastem.com+972-73-797-1613

SOURCE Kadimastem

https://www.kadimastem.com/

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Kadimastem to Present Interim Results of Cohort A of Its Phase 1/2a Clinical Trial in ALS at the 7th International Stem Cell Meeting, in Tel-Aviv,...

Every week there are numerous scientific studies published. Heres a look at some of the more interesting ones.

Glutamine Blocker Slows Cancer Growth

Researchers at Johns Hopkins developed a molecule that blocks glutamine metabolism. In their studies, they found that this slowed tumor growth, changed the tumor microenvironment, and promoted production of high-active anti-tumor T-cells. They believe it could be used across a wide spectrum of cancer types.

By targeting glutamine metabolism, we were not only able to inhibit tumor growth and change the tumor microenvironment, but also alter the T-cells in a way that we markedly enhanced immunotherapy for cancer, said Jonathan Powell, associate director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center. In the beginning, our thought was that if we could target tumor metabolism, we could achieve two goals: slow tumor growth and alter the tumor microenvironment.

The compound, JHU083, in mice, significantly decreased tumor growth and improved survival in a number of different cancer models. They also experimented on using JHU083 and a checkpoint inhibitor. Initially, we thought we would need to use the two therapies sequentially in order to avoid any potential impact of the metabolic therapy on the immunotherapy, Powell said. Remarkably, however, it turned out that the combined treatment worked best when we gave them simultaneously. We found that JHU083 was having a very positive, very direct effect on the immune cells, and we had to investigate why.

Most Foods in the US are Deemed Hyper-Palatable

Although many nutritionists and researchers have dubbed a class of foods hyper-palatable, which typically means a combination of fat, sugar, carbohydrates and sodium, there has been no specific guidelines for that class of food. Researchers published an article in Obesity that offers specific metrics to qualify hyper-palatable, and found that most foods in the U.S. met those criteria. What this means is that much of the food eaten in the U.S. is designed by food companies to light up your brain-reward neural circuit and overwhelm natural brain mechanisms to signal when weve had enough to eat.

Protein Appears Protective Against Type 2 Diabetes

Adipsin is a protein produced in body fat. It seems to protect pancreatic beta cells, which produce insulin, from destruction in type 2 diabetes. In a study of middle-aged adults, higher levels of adipsin was associated with protection from type 2 diabetes. Adipsin appears to activate a molecule called C3a, which protects and support function of beta cells. C3a also suppresses an enzyme called Dusp26 that can damage and kill beta cells. By directly blocking DUSP26 in human beta cells, the researchers found it protected the beta cells from death.

Surprising Insight into Parkinsons Disease

Researchers with Rockefeller University discovered something completely unexpectedthe affected neurons in Parkinsons may not be dead. They found they may shut down without dying and these undead neurons release molecules that shut down neighboring brain cells, which leads to the common Parkinsons symptoms. The research focused on the function of a Parkinsons protein called SATB1 in dopamine-producing neurons. SATB1s activity is decreased in Parkinsons disease. The researchers grew human stem cells into dopamine neurons in a petri dish. They then silenced the gene for SATB1.

What they found was that the neurons without SATB1 released molecules that cause inflammation and eventually senescence in neighboring neurons. The cells also showed other abnormalities, including damaged mitochondria and enlarged nuclei. None of those changes were observed in dopamine neurons with intact SATB1 or in a separate group of non-dopamine neurons without SATB1. They concluded that the senescent pathways were specific to dopamine neurons.

The Role of Enzymes in Antibiotic Synthesis

Researchers at McGill University were able to develop a technique to take ultra-high resolution 3D images of nonribosomal peptide synthetases (NRPSs). NRPSs synthesize a broad range of antibiotics, as well as molecules to fight viral infections and cancers. They discovered significantly new information about how the NRPSs work, which may lead to the production of new antibiotics.

Oxygen Deficiency Reprograms Mitochondria

The mitochondria are the energy engines of the cell. They burn oxygen and provide energy. Researchers discovered that mitochondria, under low oxygen and nutrient conditions, are rewired to use glycolysis, where sugar is fermented without oxygen. These conditions are common in cancers. The researchers identified a new signaling pathway, which may have implications for pancreatic cancer and other tumors.

Using Anthrax to Fight Bladder Cancer

Researchers at Purdue University have developed a combination of the anthrax toxin with a growth factor to kill bladder cancer cells and tumors. Bladder has a protective layer that prevents the anthrax cells from getting through, but with the addition of the growth factor, the anthrax toxin killed cancer cells within minutes without harming the normal bladder cells. The research was tested in dogs with bladder cancer who had no other treatment options. The treatment decreased the tumor size without causing any other side effects.

Link:
Research Roundup: New Molecule Slows Broad Range of Cancer Types and More - BioSpace

Late Superman actor Christopher Reeves son, Will, opened up about his late fathers legacy 15 years after his death.

Will attended the Christopher and Dana Reeve Foundations A Magical Evening gala on Thursday night where he spoke about both his famous dad, who died in 2004, as well as his mother, who died in 2006.

BOY, 10, IS YOUNGEST PERSON TO GET 'CHRISTOPHER REEVE' BREATHING DEVICE

I think his legacy is never going to go away and think that is a responsibility that I feel, to carry his and my mothers legacy on for the rest of my life and hopefully beyond that, Will told People. I think that the foundation is one way, one tangible way, that his legacy and my moms legacy will always live on. And I think the way that I, and my siblings, live our lives is another way. And I think that his impact is felt by the millions of lives that he touched.

Will Reeve arrives at The Christopher & Dana Reeve Foundation "Magical Evening" Gala on Nov. 15, 2018 in New York City. (Photo by Dia Dipasupil/Getty Images for Christopher & Dana Reeve Foundation)

The outlet notes that Will was only 3 years old when his dad was paralyzed in a 1995 horse-riding accident. Although most people remember Christopher Reeveas the man who played Superman in four movies, Will notes that he witnessed his dad overcome his physical hardships to leave a lasting impact on the world thanks to his advocacy for stem cell research and helping other people with similar paralysis.

ROBIN WILLIAMS CHEERED UP CHRISTOPHER REEVE AFTER ACCIDENT, FELT GUILT OVER JOHN BELUSHI'S DEATH, SAYS DOC

I think that the people who have the most lasting impact on culture are people who made a real difference in the world beyond whatever it is that they were initially known for, he shared. And I think that my dad is certainly one of those people he had an impact on the world well beyond his fleeting fame for being in movies. And I think that he was a change agent in the world, and those are the people who last, and that is why he has lasted.

Will works with his half-siblings Matthew and Alexandra at his parents' nonprofit dedicated to improving the quality of life for people with paralysis, an endeavorhe explained keeps him close to his late parents.

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I think that what my dad and my mom would be so proud of the three of us for, is that we dedicate a lot of time and energy to the Reeve Foundation, but we also dedicate a lot of time and energy to our own lives, and to our own jobs and to our families and to our friends, he said. Because what my mom and dad wanted was for us to be our own people, who were fortunate enough to have their guidance as a backbone, as a fundamental driver. So, what would they be happy about? That we are living our own lives in a way that I think would make them proud.

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Superman actor Christopher Reeve's son remembers him 15 years after his death: 'He had an impact' - Fox News