In 1976, pop culture icon John Travolta starred in the made-for-television movie The Boy in the Plastic Bubble about a young man with a compromised immune system. The premise of the film is that Travolta’s character has to decide between living in isolation behind a protective bubble or dying engaged with the physical world. Hollywood revisited the theme in 2001 with Bubble Boy starring Jake Gyllenhaal.
Although the movie industry makes these plots seem larger than life, they are based in reality. The characters’ compromised health is loosely based on severe combined immune deficiency (SCID). In recent decades, clinical gene therapy trials have underpinned the research that has significantly contributed to advancements in the development of therapies for this and other diseases – and these trials can be traced back to a young girl named Ashanthi DeSilva.
The four-year-old that changed history
In 1989, the parents of four-year-old Ashanthi lived with the horror that their beloved daughter was suffering from an incurable gene-based immune deficiency. She had been diagnosed at two years old after suffering a string of debilitating infections.
Her particular type of SCID was deemed adenosine deaminase (ADA) deficiency. Treatment involved regular injections of PEG-ADA, an artificial form of the ADA enzyme, to boost her T-cell count, a treatment that tends to decline in effectiveness over time. After two years of injections, Ashanthi was no longer responding to the treatment.
Without a groundbreaking change in the way ADA was dealt with, she would never reach adulthood. This type of SCID would sentence her to a short life of isolation, suffering, and death. But in 1990, Ashanthi’s parents Raj and Van DeSilva connected with geneticist French Anderson, who was lobbying for permission to move forward with human gene therapy trials.
Breaking new ground
Scientists had already established that genes could be successfully inserted into plant and animal life with remarkable results, and Stanley Cohen and Herbert Boyer had developed gene-altering techniques in the early 1970s. Cohen would later earn a Nobel Prize, and Boyer founded the first biotechnology company, Genentech. During the 1980s, the researchers’ work had spurred gene alterations to tomatoes and tobacco and even created disease-resistant corn. The possibilities seemed endless.
Despite its controversial nature and substantial pushback, Anderson’s clinical trial would take the next logical step and apply the technique of manipulating a virus to carry a corrective gene into patients. After a strenuous approval process, Anderson received permission to move forward in 1990. Ashanthi’s parents were fortunate to be in the right place at the right time and gave permission for their daughter to be implanted with the corrected gene. The alternative was certain death. The parents reportedly responded to media questions by rhetorically saying, “What choice did we have.”
Initial successes, future challenges
In conservative terms, the results of Anderson’s courageous clinical trials were nothing short of astonishing. Over the first six months, the girl’s T-cell count went vertical. She quickly tested at normal levels, and her health took a remarkable uptick over the following two years.
Ashanthi suffered no significant side effects, and the trial added other patients. In just four months, another young girl underwent successful treatment. Although doctors opted to have Ashanthi continue PEG-ADA injections at a modest rate, she was able to attend school with other children and live a relatively normal life.
Clinical gene therapy trials have not been without their setbacks. In some cases, leukemia set in after X-SCID therapy, and failures treating Wiskott-Aldrich syndrome have been reported. However, numerous trials have demonstrated significant success combating seemingly incurable or extremely difficult to treat conditions, generating considerable interest among today’s biotech and specialty pharma researchers working in rare or genetic diseases.
There are often very few, if any, existing treatment options for patients living with life-threatening or life-limiting conditions who enter gene therapy trials. If not for the path blazed by gene researchers, the fate of children such as Ashanthi would have been that of the tragic Hollywood films.
Educating & engaging the public in the future of clinical gene trials
The watershed success of Anderson’s treatment of young Ashanthi resulted in a vast field of gene therapy research and clinical trials. More than 500 gene therapies were currently in clinical trials in the first half of 2017, and thousands of people without hope of a treatment or potential cure have been positively impacted.
Going forward, researchers are delving into the possibilities of using gene therapy to fight back against otherwise incurable ailments such as diabetes, Huntington’s disease and even a variety of cancers. As these trials become more common, it will be important for researchers to educate potential volunteers and the general public about the important differences between drug and gene therapy.
Medications are often easily broken down and pass through the body relatively quickly. For all their worth, they can be temporary fixes that require repeated and ongoing treatment. Gene therapy might be a permanent solution, though the long-term impact of most gene therapies is still under investigation.
Newly introduced genes can become a permanent part of a person’s genome and can either arrest further advancement of the disease or, in some extremely limited cases, reverse the disease being treated. While gene therapy generally doesn’t reverse the damage that has already occurred, it can provide hope for patients and their families where there previously was none. That’s why the importance of clinical gene therapy trials cannot be understated.
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 Alliance for Regenerative Medicine (ARM). (2017). Q2 2017 Data Report