DDx

In this episode, we explore some of the major scientific findings – like discovering DNA – that set the stage for the development of gene therapy and its groundbreaking potential when it comes to the treatment of genetic diseases.

The very idea of gene therapy wouldn’t be imaginable had two pairs of pioneering scientists not bonded decades earlier. In 1951, a young chemist named Rosalind Franklin and her colleague Maurice Wilkins at King’s College in London were using X-ray crystallography to try and perceive the properties of a theoretical molecule known as deoxyribonucleic acid.

At the time, many scientists believed that all the genetic information about living organisms was contained in a molecule called DNA. But no one had figured out exactly what it was, or what it looked like.

After attending a presentation by Franklin, James Watson – who was also studying the topic – connected with Francis Crick. Crick had been studying the concept of base pairs – the idea that nucleic acid is composed of chemical bonds between not one but two sets of molecules, each supporting the other, much like the two sides of a ladder support the rungs in between. Excited by their shared passion, Crick and Watson in Cambridge began to build models of possible DNA structures, trying to figure out just how all the pieces fit.

Eventually, Franklin, Wilkins, Watson and Crick’s efforts joined, and DNA was discovered. Then, in the 1970s, DNA was successfully transferred from one life form to another.

Less than 50 years after Crick, Franklin, Wilkins, and Watson first showed us what this molecule looks like, genetic engineering gave us the ability to reprogram it when it isn’t working.

Scientists and doctors began to dream big: could this technology eventually cure all genetic diseases?

There was still work to be done. But, like a tiny plasmid loaded up with recombinant DNA, we were on our way.

For more education on gene therapy, visit www.genetherapynetwork.com.

Chronic vomiting, a flushed complexion, and acute agitation: can cannabis be the cause? A growing consensus among doctors suggests cannabinoid hyperemesis syndrome is real and on the rise.

Adeno-associated viral vectors, or AAVs, are the tiny shells of viruses. And today they are the most common vessels for delivering gene-based therapies. In this episode, we’ll launch into the past, present, and future of AAVs.

Imagine a rocket ship blasting off from Earth with cargo bound for a distant space station, and you have a pretty good idea what adeno-associated viral vectors are all about. But instead of ferrying hardware and supplies, AAVs carry genes.

It’s an achievement nearly six decades in the making. That might seem like a long time to tinker with something smaller than the tiniest single-celled organism. But just like building a rocket ship destined for the deep reaches of space, the development of AAV vectors required patience, persistence, and a few leaps of faith.

In the era before DNA sequencing and gene cloning, scientists in the 1960s realized that adeno-associated viral vectors could be a window into understanding genetic variations in viruses – and eventually other organisms, too.

The fact that AAVs were immunologically distinct from other viruses made them curious things.

So in the 1970s, AAV research took off in three directions. One determined that the simple AAV DNA could be rewritten and edited in a lab. The second found that although these small viruses can infect humans, they don’t replicate without a “helper virus” (such as adenovirus). In the absence of another virus, they remain latent, and appear to be of little threat to human health. The third investigated whether AAVs could become vectors for transferring genes from one organism to another.

This all culminated in 1978, when the first cloned AAV was generated and was successfully transferred to a cell of the E. coli bacterium, where it produced 50 new colonies of AAVs.

So now we had proof that adeno-associated viruses could be artificially produced, that they

could be hollowed out and filled with other genetic material, and that they could potentially be

a vector for delivering genes without harming their new host.

By the 1980s, we had the capability to build lots of viral rocket ships and fill them with genetic cargo, we just needed a destination to send them. Enter the burgeoning field of gene therapy, with its focus on developing treatments for genetic diseases like cystic fibrosis, hemophilia B, Parkinson’s, and more.

Research has continued and today, adeno-associated viral vectors are a mainstay of gene therapy development. While progress is necessarily slow, gene therapy is a science that is aiming for the stars. And with AAV vectors, they are now within our reach.

For more education on gene therapy, visit www.genetherapynetwork.com.

A patient in her mid-50s complains of foot and leg pain. She's post-menopausal with low bone density. A classic case of post-menopausal osteoporosis.

Not exactly.

And it won’t start to become clear until it gets to the point of her having repeated metatarsal bone fractures.

Let’s go back a little. It’s 2005. Our patient visits her family doctor complaining of pain in her legs and feet. But the discomfort she's experiencing isn't your typical aches and pains associated with aging.

“She develops a lot of [foot and leg] pain ... So much so that she required pain management for this pain and her gate started to become affected,” shares Dr. Katherine Dahir, a professor of medicine at Vanderbilt University, who specializes in metabolic bone disease.

Her gait becomes wobbly and she’s experiencing an acceleration of degenerative changes in her spine. An osteoporosis screening reveals she has low bone density. She’s diagnosed with post-menopausal osteoporosis and is treated with bisphosphonates, the standard of care for patients with osteoporosis.

And this is when things get much more complicated.

Although all signs show an improvement in bone density, she begins to experience metatarsal bone fractures, which is highly unusual with osteoporosis. And not only does she have these unusual fractures, the fractures will not heal.

“And so that's when you need to put your thinking cap on and try and figure out, why is this patient a treatment failure?” says Dr. Dahir.

To solve the case, the patient’s team studies her labs and finds a missing flag. “... It was called alkaline phosphatase, which is seen in a routine chemistry panel. Back at that time, it was only flagged if it was above the normal reference range because that usually indicates liver disease, but it wasn't flagged if it was below the normal reference range because that was considered to be non-significant.”

But this finding would prove to be very significant. Combined with new research at the time, it helped identify a diagnosis for this patient — showing the importance of medical research that leads to more treatment options and more hope for patients.

While skin findings can sometimes help with a diagnosis, they can also distract from other undiagnosed symptoms.

This episode is brought to you by Novartis Pharmaceuticals Corporation.

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