The Evolution of World AIDS Day: Then and Now 

TIME cover stories on AIDS through the years

A truly modern epidemic, HIV/AIDS has hit every continent on the planet and affects nearly 40 million people worldwide. Today, we celebrate World AIDS Day by commemorating those who have died from AIDS-related illness, showing support for people living with HIV, and fighting for a cure. 

World AIDS Day was first observed in 1988 and takes place on December 1st each year. The first ever global health day, the path to acceptance and scientific advancements towards HIV/AIDS hasn’t been easy. Over the past four decades, the epidemic has changed enormously and so, too, has the global agenda. Universal testing is the main key to halting the number of new infections. Scientific advances in HIV treatment have prolonged lives and, in many cases, even made the virus undetectable. But this battle is far from over. 

40 years ago, in the spring of 1981, a mystery illness began exploding across the gay communities of New York, Los Angeles and San Francisco. Men were inexplicably coming down with cancer and other mysterious illnesses. Many of them would be dead within weeks. As more cases were confirmed across the Atlantic, it become known as the ‘gay plague’. It wasn’t until 1982 that this mysterious plague earned a name: Acquired Immune Deficiency Syndrome or AIDS. The following year, scientists uncovered the culprit behind AIDS. It was a virus, which they eventually called HIV: the human immunodeficiency virus

And the disease wasn’t just targeting homosexuals. Anyone could be infected through blood, sexual intercourse, pregnancy, and breastfeeding. However, word was to slow get out and ignorance about HIV remained rampant. By 1984, as the death toll climbs, the top priority become preventing the spread of AIDS.

As the science progressed, activism intensified. AIDS patients and their loved ones began uniting all over the world to demand greater access to experimental drugs and plead their governments for more funding. In 1990, Congress passed the largest federally funded program in the US for people living with HIV/AIDS through the Ryan White CARE Act. In 1993, President Clinton set up the White House Office of National AIDS Policy and the National Institute of Health (NIH) expanded its AIDS research.

With great funding came great scientific breakthroughs for the treatment and prevention of HIV. FDA’s approval of Atripla in 2006 marked a watershed in HIV treatment. By combining three different antiviral medications- efavirenz, emtricitabine and tenofovir- into a single fixed-dose combination pill, HIV treatment became a once-daily single tablet regimen. Between 2005 and 2018, there was a 45% decline in AIDS related deaths worldwide.

Despite tremendous biomedical and scientific progress, there’s still no cure for AIDS. As people with HIV live longer, AIDS is a topic that has drifted from the headlines. When World AIDS Day was first established in 1988, the world looked very different to how it is today. As we celebrate the progress of the past four decades on this historic day, we mustn’t lose sight of the ultimate goal that lays ahead of us. CIRM has committed nearly $80 million to HIV/AIDS research including funding four separate clinical trials.

Bridges Scholar Spotlight: Samira Alwahabi

For more than a decade, CIRM has funded a number of educational and research training programs to give students the opportunity to explore stem cell science. One such project, the Bridges to Stem Cell Research program, helps train future generation of scientists by preparing undergraduate and master’s students from several California universities for careers in stem cell research.

Last summer, the Pacific Division of AAAS organized a ‘Moving on from COVID-19’ virtual forum specifically focused on students of science presenting their future career and research plans through 3-5 minute descriptive videos. 

Samira Alwahabi, a Bridges scholar and undergraduate student majoring in Biological Sciences at California State University, Fullerton was one of the many participants who submitted a video detailing their current work and future aspirations. Alwahabi is a CIRM intern conducting research in the Kuo lab at the Stanford University School of Medicine where she focuses on the identification and characterization of human distal lung stem cells as well as the effects of the novel SARS-CoV-2 virus on the human distal lung through the use of organoids. Her video, which you can watch below, was recognized for “Best Video Submission by an Undergraduate Student.” 

We reached out to Samira to congratulate her and she shared a few words with us about her experience with the Bridges program:

I am very grateful to the CSUF Bridges to Stem Cell Research program for giving me the opportunity to pursue research in the Kuo Lab at Stanford University. The past 11 months have been nothing less than exceptional! I have learned more than I could have even imagined and have been able to really solidify my future career goals through hands-on practice and interactions with professionals at all levels in the field of medical research. The CIRM Bridges program has allowed me to better understand how medical advancements are made and helped to further strengthen my interest in medicine. My future career goals include a career in medicine as a physician, where I will be able to use my research experience to better understand medical innovations that translate into improved quality of care for my patients. 

Congratulations Samira!

One step closer to making ‘off-the-shelf’ immune cell therapy for cancer a reality 

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Immunotherapy is a type of cancer treatment that uses a person’s own immune system to fight cancer. It comes in a variety of forms including targeted antibodies, cancer vaccines, and adoptive cell therapies. While immunotherapies have revolutionized the treatment of aggressive cancers in recent decades, they must be created on a patient-specific basis and as a result can be time consuming to manufacture/process and incredibly costly to patients already bearing the incalculable human cost of suffering from the cruelest disease.

Fortunately, the rapid progress that has led to the present era of cancer immunotherapy is expected to continue as scientists look for ways to improve efficacy and reduce cost. Just this week, a CIRM-funded study published in Cell Reports Medicine revealed a critical step forward in the development of an “off-the-shelf” cancer immunotherapy by researchers at UCLA. “We want cell therapies that can be mass-produced, frozen and shipped to hospitals around the world,” explains Lili Yang, the study’s senior author. 

Lili Yang, the study’s senior author and a member of UCLA’s Broad Stem Cell Research Center

In order to fulfil this ambitious goal, Yang and her colleagues developed a new method for producing large numbers of a specialized T cell known as invariant natural killer T (iNKT) cells. iNKT cells are rare but powerful immune cells that don’t carry the risk of graft-versus-host disease, which occurs when transplanted cells attack a recipient’s body, making them better suited to treat a wide range of patients with various cancers.

Using stem cells from donor cord-blood and peripheral blood samples, the team of researchers discovered that one cord blood donation could produce up to 5,000 doses of the therapy and one peripheral blood donation could produce up to 300,000 doses. The high yield of the resulting cells, called hematopoietic stem cell-engineered iNKT (HSC–iNKT) cells,could dramatically reduce the cost of producing immune cell products in the future. 

In order to test the efficacy of the HSC–iNKT cells, researchers conducted two very important tests. First, they compared its cancer fighting abilities to another set of immune cells called natural killer cells. The results were promising. The HSC–iNKT cells were significantly better at killing several types of tumor cells such as leukemia, melanoma, and lung cancer. Then, the HSC–iNKT cells were frozen and thawed, just as they would be if they were to one day become an off-the-shelf cell therapy. Researchers were once again delighted when they discovered that the HSC–iNKT cells sustained their tumor-killing efficacy.

Next, Yang and her team added a chimeric antigen receptor (CAR) to the HSC–iNKT cells. CAR is a specialized molecule that can enable immune cells to recognize and kill a specific type of cancer. When tested in the lab, researchers found that CAR-equipped HSC–iNKT cells eliminated the specific cancerous tumors they were programmed to destroy. 

This study was made possible in part by three grants from CIRM.

Old therapies inspire new hope for treatment of pediatric brain tumors

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Image courtesy St. Jude Children’s Research Hospital

A recent study led by John Hopkins Medicine has found that combining two ‘old therapies’ can offer a surprising new purpose – fighting Medulloblastoma, the most common malignant brain tumor in children. The fast-growing cancerous tumor originates in the brain or spinal cord and has traditionally been treated with surgery to remove the tumor followed by radiation and chemotherapy. 

The prospective therapy which comprises of copper ions and Disulfiram (DSF-Cu++), paves the way toward a successful treatment that can be used alone or in conjunction with traditional therapy. “Disulfiram, [is] a medication that’s been used for nearly 70 years to treat chronic alcoholism,” explains Betty Tyler, the study’s senior author and associate professor of neurosurgery at Johns Hopkins. “It has great promise being ‘repurposed’ as an anticancer agent, especially when it is complexed with metal ions such as copper.”

The researchers tested the anticancer activity of DSF-Cu++ and, in their attempts to define what it targeted at the molecular level to achieve these effects, were able to highlight four key findings.

First, the team of researchers found that DSF-Cu++ blocks two biological pathways in medulloblastomas that the cancer cells need in order to remove proteins threatening their survival. With these pathways blocked, these proteins accumulate in the tumor and cause the malignant cells to die, leaving them to eventually be removed by the body’s own immune system. 

Second, the researchers discovered that just a few hours of exposure to DSF-Cu++ not only kills medulloblastoma cells but can also effectively reduce the cancer stem cells responsible for their creation. 

The third finding in the study revealed that DSF-CU++ keeps cancer cells from recovering. By impairing the ability of medulloblastoma cells to repair the damage done to their DNA, DSF-CU++ enhances the cell killing power of the treatment.

Lastly, the promising combo of DSF-CU++ demonstrated significant increases in prolonging survival days of mice whose brains were implanted with two subtypes of medulloblastoma. 

Reprogramming brain cells to restore vision after a stroke

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About one third of stroke survivors experience vision loss. It can be a devastating side effect as most patients will not fully recover their vision and there are currently no reliable treatments available. But thanks to a collaborative effort by two teams of researchers from Purdue University and Jinan University in China, there may be a way to use gene therapy to recover lost vision after a stroke.

A stroke happens when part of the brain is starved of oxygen which can result in death of brain cells or neurons. Oftentimes this is caused by a blockage in an artery in the brain. Given the location of these vital arteries, most strokes lead to loss of motor function and in some cases, permanent vision loss.

The brain is an incredible machine and capable of remapping its neural pathways enough to restore some visual function, but this isn’t always the case. The neurons that are destroyed in the process of experiencing a stroke do not regenerate and lose their ability to communicate/transmit information between different areas of the brain, and between the brain and the rest of the nervous system.

Two research teams, one led by Alexander Chubykin at Purdue University’s and the other led by Gong Chen at Jinan University, have taken a different approach to neural regeneration by reprogramming local glial cells into neurons, therefore restoring connections between the old neurons and the newly reprogrammed neurons.

In a news release, Dr. Chubykin says the results in the lab look promising. “We can watch the mice get their vision back. We don’t have to implant new cells, so there’s no immunogenic rejection. This process is easier to do than stem cell therapy, and there’s less damage.”

The collaborative research, published in the journal Frontiers in Cell and Developmental Biology, is promising not only in aiding with vision restoration after a stroke but could also lead to similar treatment for reestablishing motor function. Visual function is easier than motor skills to measure accurately and the scientists are looking into the effectiveness of this procedure in live mice using advanced optical imaging tools. If the study continues to provide positive results, it might not be long before human trials are started. 

CIRM is also funding clinical trials to help repair vision loss and to help people recovering from a stroke.

Wit, wisdom and a glimpse into the future

As of this moment, there are over two million podcasts and over 48 million episodes to listen to on your favorite listening device. If you’re a true crime enthusiast like me, you’ve surely heard of Casefile or one of the other 94 podcasts on the topic. But what if you’re looking for something a little less ghastly and a little more uplifting?

Dr. Daylon James, co-host of The Stem Cell Podcast

The Stem Cell Podcast is an informative and entertaining resource for scientists and science enthusiasts (or really, anyone) interested in learning about the latest developments in stem cell research.

Dr. Arun Sharma, co-host of The Stem Cell Podcast

On their latest episode, dynamic co-hosts and research scientists Dr. Daylon James and Dr. Arun Sharma sit down with our President & CEO, Dr. Maria Millan, to discuss the impact of California’s culture of innovation on CIRM, the challenge of balancing hope vs. hype in the context of stem cell research/therapies, and the evolution of the agency over the past 15 years.

Listen on as Dr. Millan highlights some of CIRM’s greatest victories and shares our mission for the future.