The Cure Factory

UCLA is on a mission to make the world’s most harrowing ailments—everything from bubble-baby disease to HIV—relics of the past.

By WP BrandStudio

In 2015, the parents of a three-month-old boy in Lebanon were confronted by a devastating diagnosis: their infant son likely wouldn’t survive past the age of two. A doctor in Beirut explained to them that their son suffered from an incredibly rare genetic disorder called ADA-SCID. Those with the disease are born with mutations in the ADA gene, which is vital to the development and maintenance of the immune system. Commonly known as bubble-baby disease, the disorder renders people defenseless against any bacterial or viral infections; for babies afflicted with it, even the common cold can be deadly.

Distraught, the boy’s parents reached out to a Michigan-based physician in the family, who gave them a glimmer of hope by informing them of a potential cure available in southern California on the campus of UCLA. A few months later, the baby was transported 7,500 miles to begin treatment under the care of Donald B. Kohn, M.D., a physician, scientist and professor working at UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research and Mattel Children’s Hospital.

“When he arrived he was so sick—he was six months of age and the weight of a newborn,” said Kohn. “It turned out he had viral pneumonia, so he wound up spending more than a month on a ventilator in the pediatric ICU and came close to dying a few times.” As soon as the boy was stabilized, he began undergoing the stem-cell-based gene therapy that Kohn pioneered. Since 2005, his technique has successfully treated more than 40 babies with the disease, although the infant patients were usually admitted when they were younger and healthier. Within a few months, the boy from Lebanon too was cured. “He’s now on no medicines and is growing well,” said Kohn happily.

His discovery is just one example of the incredible success UCLA has had seeking treatments for the world’s most devastating diseases, spanning from the first genetics-based treatments for breast cancer to the discovery of the structure of the proteins underlying Alzheimer’s disease. Driven by a spirit of resilience and ingenuity, the institution is committed to a fundamental belief: that no illness is incurable.

A Creative Approach to Combatting AIDS

“When I was a graduate student in the early Eighties, I spent several weeks agonizing over whether I wanted to work with a virus that would basically kill you,” says Jerome Zack, Ph.D., explaining how he decided to become one of the first researchers tackling the then-nascent pandemic of HIV, the virus that causes AIDS. “At that time, we didn’t really know about transmission and how one protects oneself against this. But I thought about it and really felt that if I was going to spend many, many hours a day in a lab, I wanted to do it fighting something that was important.”

A colleague of Kohn’s at UCLA’s Broad Stem Cell Research Center, Zack is also the director of the UCLA Center for AIDS Research, a federal program which distributes approximately $2.5 million in funding each year to support research on HIV/AIDS. Over the past three decades, Zack’s own research has focused on understanding how the HIV virus replicates with the hope of uncovering better ways to combat it and, potentially, even find a cure. These days what sets his team’s research apart, he says, is that they primarily rely on animal studies rather than cell cultures in test tubes. This tactic offers far more accurate insights into how the virus actually replicates inside a living host.

Zack and his team transplant human immune tissues into specially engineered mice that don’t have their own immune system and proceed to infect the human tissues with HIV. The mice themselves are never infected by HIV and also don’t have an immune response capable of rejecting the human tissue, so they act as ideal hosts.

“Once the infected human tissues are inside this mouse body, we can study how the virus behaves in that animal, and we can try to establish new therapies,” Zack explained. The research has led to an innovative method of treatment he describes as “kick and kill,” in which HIV viruses are kept in a dormant state by antiretroviral drugs—the same class of drugs that are already prescribed to HIV and AIDS patients—and then selectively activated as targets for new experimental treatments to attack. “Basically, we tickle, or kick, the cell so the virus peaks its head out, and we can now see it and kill that cell,” said Zack.

Zack believes this approach, although not yet ready for clinical trials, could become a powerful component of a new multipronged HIV/AIDS treatment methodology alongside other avenues his team is exploring, such as attempting to strengthen human immunity by inserting new genes into blood-forming stem cells. “Each of these approaches currently suffers from some technical drawback, but those can be overcome with time and with new technologies,” he said. “And I think that gives hope for a bright future for the treatment of HIV.”

Forging a Healthier Future Against All Odds

Ironically, the HIV virus plays a crucial role in the cure that Kohn has developed for bubble-baby disease. Kohn’s therapy works by extracting stem cells from a sick baby’s bone marrow, inserting a new normal copy of the ADA gene into the cells and then injecting the repaired stem cells back into the patient. The new stem cells quickly begin rebuilding babies’ immune systems from the ground up. Because of its evolved ability to get into human cells with high efficiency, HIV—in a safe, modified form—acts as an ideal vehicle for inserting the immunity-forming genes.

This is the “classical” approach to gene therapy, Kohn says. Yet he sees potentially even more effective methods, such as the popular gene-editing technique known as CRISPR/Cas9, emerging on the horizon.

“I think it’s very exciting. Decades of studying genes, molecular biology, and viruses has led to a whole new way to treat diseases, not by giving medicines to treat the symptoms downstream but actually getting to the root cause of these diseases and permanently fixing them using personalized medicine,” he says. “Our technical capabilities are continuing to grow, and hopefully we’ll soon have better therapies for many of the diseases that affect us.”

Over the past few years, empowered by these capabilities, many other researchers at UCLA have made bold strides forward in finding treatments to cruel diseases. Doctors at the UCLA Jonsson Comprehensive Cancer Center, for example, recently unveiled a new approach to treating advanced prostate cancer that relies on a more personalized use of hormonal therapy. In another case just a few years ago, a team from a number of different UCLA facilities published the results of a surprising study in which the affects of cognitive decline in Alzheimer’s patients were reversed through customized health regimens.

As with most other innovative fields, paving new ground in medicine isn’t easy. For the scientists at UCLA, false starts, failures and dead ends are a regular part of the process. “There are going to be technical and theoretical hurdles that stop, sidetrack, or slow down your research,” cautioned Zack. “You encounter these roadblocks, and it’s discouraging, but you have to be able to overcome them.”

That resilience pays off when the lab work yields breakthroughs. “When you see a good result, and you’re the first person on the planet to ever see this, it really moves you forward and gets you excited,” Zack added.

Kohn echoed that perspective. “Nothing in this is easy. Everyone’s job has challenges, but the rewards [in this field] are so great,” he said. “When you succeed, and you know that you can help little babies lead normal lives, what could be better than that?”