S5, E04: Checking Vitals: The Disruptors

Gina Mullane (00:06):
Hi, I'm Gina Mullane.

Todd Poley (00:07):
And I'm Todd Poley.

Gina Mullane (00:09):
Welcome to Checking Vitals, our final Vital Science episode of 2023. It's been an inspiring season, hasn't it Todd?

Todd Poley (00:18):
Absolutely Gina. We've had the privilege of sharing the journeys of some incredible disrupters in the drug development space.

Gina Mullane (00:25):
We have heard some truly remarkable stories, but the three disrupters we are recapping in today's episode really stood out as being trailblazers in their respective fields.

Todd Poley (00:37):
And what's amazing is that these three individuals come from completely different backgrounds and have unique therapeutic goals, but they've all faced similar challenges.

Gina Mullane (00:49):
Yes, but I think we've heard some common themes throughout the season, like just how hard it can be to bring a therapy to market when it isn't a so-called Blockbuster drug. It requires such tenacity and resourcefulness and connecting experts really across the entire scientific community.

Todd Poley (01:08):
Right. These disrupters rolled up their sleeves and did everything from conducting foundational research to recruiting scientists around the globe to overcoming regulatory hurdles.

Gina Mullane (01:21):
And so often it was fueled by a personal connection to the cause. It was certainly the case for our first disrupter, Valerie Estess, co-founder of Project ALS.

Valerie Estess (01:35):
The legacy for Project ALS is that we all are in this together. The love of sisters is a big thing. It kicked off a movement that I think is growing in momentum and there's lots of progress to be hopeful about, but again, I think the legacy for Project ALS is not just a blind hope. It's hope based on aggressive, rational research. It's the only way we're going to get there and we're committed to that to the end.

Gina Mulane (02:22):
Valerie was driven to establish Project ALS when her sister Jenifer was diagnosed at the age of 35. What began as a race to find treatment for Jennifer who ultimately passed away from the disease became a mission to put ALS on the research roadmap.

Todd Poley (02:39):
Yeah, what really put into perspective for me was when Valerie told us that at the time Project ALS was founded back in 1998, there was only two known genes associated with ALS affecting a small subset of patients. But that was before Project ALS established the first freestanding privately funded stem cell research lab in the US. Thanks in large part, to this lab's research, we now know that there are over 50 genes linked to this disease.

Gina Mullane (03:07):
I believe it was in developing a therapeutic to fight one of the less common genetic mutations, the FUS ALS that Charles River crossed paths with Project ALS. Valerie was once again racing to save a life. This time it was that of Jaci Hermstad, a patient whose twin sister had died of the disease, and that's when Project ALS connected with Dr. Lauren Black here at Charles River, who was able to provide the FDA with the data needed to approve Jaci's ASO therapy.

Todd Poley (03:39):
Yeah, it's a heart-wrenching story Gina, but it's also a testament to the power and legacy of collaboration and drug development. Sadly, Jaci passed away. However, Ionis Pharmaceuticals is sponsoring a phase three clinical trial of the drug informally known as Jacifusen, and this trial could potentially pave the way for personalized treatments for others facing similar genetic ALS challenges.

Gina Mullane (04:06):
It is truly amazing that the doors for genetic therapies are opening for neurodegenerative disease. We also heard evidence of this when we spoke with our next disruptor, Lisa Deschamps, and she's the CEO of AviadoBio.

Todd Poley (04:22):
That's right. Lisa is also focused on conditions that have an unmet need for therapy like frontotemporal dementia. FTD is similar to the other therapeutic areas in that it is a long and rigorous road to market, but as Lisa discussed at length, there's an added layer of complexity at the biological level due to the blood-brain barrier. And while it's meant to protect us, it can actually become a hurdle in delivering therapies to the brain.

Lisa Deschamps (04:54):
If we can crack this delivery hurdle that many companies have faced and will continue to face with these unique and bold approaches, again around enhanced construct, groups of administration, different delivery technologies, I believe we could really make huge advancements in certainly FTD and ALS, but even more broadly in all neurological conditions.

Gina Mullane (05:24):
FTD is a particularly devastating condition that leads to a wide range of symptoms from executive function and language deficits to even personality and behavior changes. And AviadoBio is focusing on a specific subset of FTD patients who have a genetic mutation in their GRN gene.

Todd Poley (05:48):
That's right, and I'm looking back at my notes here. On average, these patients survive only five to seven years from the time of diagnosis, and there are currently no treatment options available for the thousands carrying this mutation.

Gina Mullane (06:03):
Yeah, those are some sobering statistics Todd. I can see why Lisa has worked so hard to find a workaround for administration. Her team is using a commonly used vector and other gene therapies called AAV9, and this is the plot twist here. They're administering it directly to the thalamus. As the central relay hub of the brain, using the thalamus allows developers to minimize the required dosage while they're able to maximize the therapeutic benefits.

Todd Poley (06:33):
Wow. Well, this program holds a lot of promise for those battling FTD, not to mention other applications it may have in neurodegenerative disease. And there may be even more advancements ahead now that the company has a partner for spinal administration as well.

Gina Mullane (06:51):
Spinal administration. Well, maybe we should introduce Lisa to our third and final disrupter on today's episode. That's Dr. Wise Young. He's an expert in the field of spinal cord injury and a founding director of the W.M. Keck Center for Collaborative Neuroscience at Rutgers University.

Todd Poley (07:10):
The research coming out of the Keck Center could lead us to a new future of treatment for the 12,000 Americans who suffer from spinal cord injuries each year. SCIs are often the result of unexpected accidents like car crashes or machinery incidents that often cause irreversible trauma to the spine.

Gina Mullane (07:29):
But Dr. Young is asking a bold question, what if this damage is reversible after all? What if we could stimulate neuro regeneration enabling the regrowth of neurons damaged during SCIs?

Dr. Wise Young (07:45):
But once a neuro degeneration has happened, boy, I would say 100% of neurologists will tell you none of those neurons are ever coming back. But wouldn't it be nice if it did come back? It's not just nice. It would mean something very different for humankind. Aging could be essentially cured if we could bring neurons back.

Todd Poley (08:17):
It's a revolutionary concept, and as Dr. Young told us, it all hinges on having a quality animal model for research.

Gina Mullane (08:25):
That is right, Todd. Dr. Young has long relied on Charles Rivers RNU model, which can receive cells from other animals without immune rejection. It's a perfect tool for studying the effects of cell-based therapies.

Todd Poley (08:39):
And let's not forget the critical role of umbilical cord blood cells in this research. Exosomes found in umbilical cord blood are proving to be a game changer. These microscopic particles can stimulate neurogenesis, the growth of new neurons in the brain.

Gina Mullane (08:54):
It is truly amazing. As Dr. Young shared umbilical cord blood contains an astonishing 1 trillion exosomes per milliliter compared to 1 billion in adult blood. These exosomes not only stimulate cell growth, but they do so without causing tumors.

Todd Poley (09:13):
Yeah, it's hard to even imagine the implications of a therapy like this if successful in clinical trials, treating brain damage, healing spinal cord injuries, potentially reversing the effects of aging. But I guess I digress.

Gina Mullane (09:29):
It is hard not to get excited about these discoveries.

Todd Poley (09:33):
Yeah, glad to hear it isn't just me. I like to think this podcast offers some hope to our listeners too and sends the message to patients out there awaiting treatment that help is on the way.

Gina Mullane (09:44):
I couldn't agree more Todd and I can't think of a better note to end on as we wrap up 2023.

Todd Poley (09:51):
But don't worry listeners, we will be back with more stories of scientific discovery and therapeutic innovation in January 2024. So be sure to listen and subscribe to never miss an episode.

Gina Mullane (10:05):
And until then, we wish you the happiest of holidays. Thanks for listening.