Gene therapy – a historical overview and future prospects
Nov 13 , 2019

Gene therapy – a historical overview and future prospects

Humanity has faced many deadly diseases over the course of its history. Infectious diseases took countless lives. They didn’t choose their victims; they struck the young and old with equal impunity.

Fast-forward to 2019 and we see that diseases, mostly noncommunicable and age-related, are now killing our loved ones. People who inherit bad genes from their parents tend to die young. Their demise often comes as a surprise because dying young is much less common today than it was just a century ago. As a result, many families around the world carry this tragic burden across generations.

Age-related diseases are a huge problem today since people are living longer, but also living longer in poor health. Death by infectious disease is now uncommon. Instead, we are facing a new foe – a foe many people refuse to acknowledge. We watch our valuable resources slowly being chiseled away, doing nothing because we believe we are powerless. “It has to be that way,” some people would say. “It’s good for us and, after all, it’s natural.”

But just a hundred years ago it was perfectly normal to die of an infectious disease long before reaching old age – or even middle age.

We are at the beginning of a biotech revolution. This revolution has the potential to drastically improve our lives and cure previously untreatable diseases. This, of course, includes biological aging. There are several promising approaches, but gene therapy stands head and shoulders above the rest.

To understand why this treatment has such immense potential (which, at this time is already beginning to be realized at breakneck speed), we need to look at its history. Only then can we understand where we are and what we should expect in the future.

But, before we proceed, we need to ask a basic question:

What is Gene Therapy?

Gene therapy involves adding, altering, or silencing genes to treat or prevent disease. Several different approaches are being tested right now, but the most promising are:

  • Deactivation of mutated genes that are not working as they should.
  • Complete replacement of faulty genes with healthy counterparts.
  • Addition of new genes that can help the body fight a condition or conditions on its own.

The first gene therapy trial took place in 1990 and, as of March 2019, there are 372 clinical trials underway.

Early History

In 1972 Richard Roblin and Theodore Friedmann published a paper called Gene therapy for human genetic disease? The paper focused on the possible applications of using functional DNA to treat different genetic conditions. Many scientists accepted this idea, but the authors were cautious. They pointed out that we still didn’t understand the basics and that more research was needed before the science could move forward.

18 years after the release of this landmark paper, the first clinical trials for gene therapy began. Two girls, Ashanthi DeSilva and Cindy Kisik, suffering from a rare genetic disease known as Severe Combined Immunodeficiency (SCID).

Both patients received a new copy of the ADA gene through a viral vector (a vector is a way to deliver genes into a cell). The lack of the ADA enzyme left the girls’ immune systems vulnerable. As a result, they were at constant risk for potentially deadly infections. The new genes were inserted into their T-cells and both girls started to recover. Their immune function improved significantly and, as a result, they began living without fear.

Gene therapies soon hit a major roadblock, a roadblock that set it back (at least) a decade.

The Gelsinger Incident

In 1999 an 18-year-old named Jesse Gelsinger signed up for a gene therapy trial being conducted by the University of Pennsylvania. Jesse was suffering from a rare yet devastating genetic disorder involving a mutation in his OTC gene. It caused the ammonia to accumulate in the blood. His condition wasn’t terminal, but he wanted to help others overcome it.

The appointment was set for September 9. Jesse received the therapy four days later. Sadly, his immune response was too strong and he fell into a coma. He passed away shortly thereafter.

The world was shocked. The incident drew the attention of the media and public health agencies. Public pressure forced the FDA to abandon all gene therapy clinical trials in the US. Many experts believed we were moving ahead too fast for our own good.

Jesse’s fate is tragic, but the decision to stop the entire field from advancing was short-sighted. Many lives were lost because people with terminal conditions had no way to access (potentially) life-saving therapies.

Recovery and The Glorious Comeback

The Gelsinger incident was a bitter lesson. To continue the trials, better safety measures were needed. In other words, we needed safer viral vectors and more rigorous placebo-controlled studies. It took some time for the field to regain its momentum.

In 2003 China became one of the first countries to approve a functional gene therapy. More precisely, they approved Gendicine to treat head and neck cancers. Eight years later Russia approved Neovasculgen for peripheral artery disease. This was a sign that gene therapy was on its way to Europe as well. In 2012 the European Commission approved the use of Glybera for Lipoprotein Lipase Deficiency. While it didn’t achieve the market success UniQure expected, this didn’t prevent other gene therapies from gaining approval.

2017 was an especially important year, ushering in the first FDA approved gene therapy – Luxturna. This AAV-based therapy became a viable option for patients suffering from vision loss due to a mutation in their RPE65 gene. Gene therapy is now allowing the blind to see.

All this goes to show that gene therapy is back and stronger than ever. Yet this is only the beginning.

Where Are We Now?

We are in a much different place than we were in the 90s. We understand the process in much more detail and have much sophisticated safety measures. The number of approved gene therapies is set to explode in the near future. More and more devastating conditions are now becoming treatable targets.

Beta-thalassemia is a perfect example. Even though it is a fairly common blood disorder, there was no viable way to treat it. As a result, patients would have to undergo repeated surgeries and suffer from various complications. That’s why the approval of Zynteglo really was a game-changer.

Recently the FDA predicted that we are going to see 10-20 new gene therapies every year by 2025.

The Future of Healthcare

We have the power to create the future by recreating ourselves. No one knows that better than BioViva USA and Integrated Health Systems. IHS allows patients to take full advantage of the cutting edge of modern medicine. They are true industry pioneers with top industry experts on their team.

The main target for IHS and BioViva is biological aging. In order to truly overcome cancer, heart disease, Alzheimer’s disease, and many other age-related issues, we need to target the root cause of these problems: aging itself.

If you want to learn more, feel free to visit their website. Age-related diseases need no longer hold our fates captive. We have the option to be free from these horrific ailments. It’s up to us, here and now, to use the marvels of modern medicine to free ourselves from them.

Adam Alonzi

Adam Alonzi is a writer, biotechnologist, documentary maker, futurist, inventor, programmer, and author two novels. He is an analyst for the Millennium Project, and Head of Social Media and Content Creation for BioViva Sciences. Listen to his podcasts here. Read his blog here.