Some big trends to discuss this month, as well as one-off headlines. I have clinical updates on epilepsy, tooth regeneration and Parkinson’s – a disease area quickly becoming an RMNU🔬 staple, given all the movement in this field! Read on, bookmark for later, or send to a colleague.
Pick of the Month
March 26 is Epilepsy Awareness Day in Canada
Phase III trial for epilepsy cell therapy
About one-third of adults with epilepsy, and up to a quarter of afflicted children, have difficulty controlling their epilepsy with medications. With limited treatment options remaining, some patients turn to resective brain surgeries that – while ameliorating seizures – can result in other serious functional impairments.
Neurona Therapeutics is developing an allogeneic, or “off-the-shelf” cell therapy for drug-resistant seizures (NRTX-1001) by bringing balance back to the brain. It’s been shown that GABA neurons – an inhibitory cell type – can counteract the excessive activity or excitation that occurs during a seizure. The aim is to leverage this power by delivering lab-created GABA neurons to disease-linked neuron populations.
NRTX-1001 is manufactured by differentiating human embryonic stem cells to GABA neurons. The cells are then injected into the temporal lobes of patients with seizures stemming from this region. Their Phase I/II trials looked at unilateral and bilateral cases, with work still ongoing. The positive results presented so far with respect to safety (no adverse events attributed to the therapy), but also preliminary efficacy, are spurring the jump to Phase III: In the low-dose group of their unilateral study (n=5), there was a 92 per cent median decrease in disabling seizures relative to baseline measurements 7-12 months post-injection. For their higher dose group (also n=5), 7-12-month data are not yet available, but the researchers are reporting a 78 per cent median drop for the 4-6-month period post-injection.
As a neuroscientist with a deep appreciation for the complexity of brain circuits, I just want to take a moment to emphasize how interesting cell therapies for neurological diseases truly are. The fact that you can send new cells into the brain – relief workers without any instructions or knowledge of the situation on the ground – and they’re able to work with the locals and interpret environmental cues well enough to not only integrate, but also create these early improvements we’re seeing… that’s really something.
The drug was given an RMAT designation in 2024, which helped the team reach Phase III sooner. While early results are promising, larger patient cohorts will be necessary to determine the therapy’s true efficacy. Still, this appears to be the most advanced drug of this nature for epilepsy, so it’s one to watch!
Growing new teeth in vivo
I’ve wanted to write a proper highlight about this topic for a while now, given all the important work being done in the field!
- In brief: Katsu Takahashi’s progress.
In my post-holiday edition released last month, many big headlines needed coverage as main features. That being said, one of my additional recommendations from December was Takahashi’s new Phase I clinical trial examining a simple but promising approach: monoclonal antibodies against USAG-1 in healthy adults missing a tooth. Preclinical studies featured compelling pictures of results in mice and ferrets with fully-formed replacement teeth, so there appears to be a lot of optimism around this investigation at the moment. While the clinical trial is focusing on healthy baseline subjects, the medicine will ultimately be geared towards individuals with congenitally missing teeth.
Curious for more? Read this earlier blog post by Peace Chukwu.
- The bioengineering approach to tooth regeneration.
Now, for the February headline: A team of researchers at Tufts University is also making progress on this front and has managed to grow tooth-like structures in adult minipigs. Their approach? Bioengineered tooth buds. They make them by seeding dental stem cells onto a scaffold made from decellularized tooth bud ECM, with materials sourced from pig jawbones and extracted human teeth. These engineered tooth buds are then implanted into extraction sockets where a minipig’s lost tooth used to be. It’s a completely different approach to Takahashi’s team but, as you can see, researchers are attacking toothlessness from all sides.
Zhang and Yelick did ultimately observe the formation of mature tooth tissue, and while they weren’t perfect in shape or size, the end product did ultimately bear resemblance to the true, all-coveted replacement. They’re not quite ready for human studies according to this NPR Short Wave, but the more options we have down the line, the better. That’s especially true depending on which indication related to tooth loss each treatment is being applied for.
More work to regenerate the Parkinsonian brain
Last month, I updated you on BlueRock’s jump into phase III trials. This month, two more headlines from competitors have crossed my desk:
- AskBio’s RMAT designation for their Parkinson’s disease (PD) gene therapy
Positive Phase Ib data at 36 months led to the FDA’s decision on this new investigational medicine. Now called AB-1005, the drug was formerly referred to as AAV2-GDNF – and yes, the old name is far more literal! It’s an AAV2 packaged with a transgene for human glial cell-derived neurotrophic factor (GDNF) targeted to the putamen, similar to PD stem cell therapies. In preclinical studies, GDNF has been found to enhance the survival and differentiation of dopaminergic neurons, so the aim of this intervention is thus to slow disease progression and ameliorate motor function in PD patients.
I’ll also mention that AskBio is an owned and independently-operated subsidiary of Bayer AG.
Thanks to a lack of adverse events and positive trends reported for Phase I outcomes, enrollment is now ongoing for a Phase II study, called REGENERATE-PD.
- A new autologous iPSC-derived dopamine cell replacement trial
Preclinical results laid out in this February paper by Jeon et al. have set the stage for a new Phase I clinical trial that’s currently recruiting. Fibroblasts were collected from human patients with PD, reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated into dopaminergic progenitors. These progenitors are then delivered to rodent models of the disease. The clinical trial will be highly similar in format, except that the final recipients of the reprogrammed cells will be eight human PD patients. While a commonly cited advantage of iPSCs is that they can be used with minimal fear of immune rejection, I think it’s an open question as to whether sourcing the cells from a healthy donor might yield stronger or more long-lasting outcomes – especially if genetic elements are in play for a specific patient’s disease etiology. I found some validation regarding this concern in a recent review on the matter. Ultimately, time and trials will tell which is the better approach for whom, especially as scientists try to avoid immunosuppressants and keep infection or cancer risks low. There are pros and cons to any cell therapy approach, and we’re still building those arguments – especially with respect to efficacy data.
If the iPSC-based approach to PD cell therapy sounds familiar to you, perhaps you’re recalling Aspen Neuroscience’s ongoing trial, which I covered back in the May 2024 edition of RMNU🔬. These two groups appear to be testing highly similar concepts, so keep an eye on both – and as always, I’ll update you as the data start to flow.
Additional recommendations
Risdiplam for Prenatal Therapy of Spinal Muscular Atrophy. A rare genetic disorder, spinal muscular atrophy has been treated in utero for the first time. So far, all signs point to success as the baby girl in question appears healthy at two and a half years old. Note that the child will likely have to be on medication for the rest of her life, and longer-term monitoring will be necessary. It’s also an n of one. Still, a highly compelling case indeed.
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. These two supplements are widely discussed for an array of reasons and indications. This one isn’t perfectly in line with the regenerative medicine theme, but I’ll permit it because of how closely related longevity science tends to be. In addition, a lot of us already take these supplements for other reasons, whether or not these findings hold or shake out to be solid. I am not endorsing any supplements here, nor am I a medical doctor positioned to suggest them to others, I only highlight the science. Happy to encourage more exercise though, as I don’t think I need a medical degree for that one. Further reading and analysis can be found at Nature News: Omega-3 supplements slow biological ageing.
Nature-inspired platform nanotechnology for RNA delivery to myeloid cells and their bone marrow progenitors. Many companies and research groups are zeroed in on RNA delivery right now – I’m seeing it come up quite a bit.
New stem cell transplant approach offers potential sickle cell cure.
Bacteria, stem cells and cancer.
Maternal gut microbiota influence stem cell function in offspring.
Retina Stem Cell Treatment to Come Under National Health Insurance.
Experimental cell therapy trial treats first Sjögren’s disease patient.
Stem cell therapy found to reduce itch, pain in RDEB children in trial.
Decoding functional hematopoietic progenitor cells in the adult human lung.
Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets.
Mesoblast prices pediatric stem cell treatment at $1.55 million.
Astrocyte heterogeneity reveals region-specific astrogenesis in the white matter.
Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.
Identification of Meibomian gland stem cell populations and mechanisms of aging.
Neural stem cell relay from B1 to B2 cells in the adult mouse ventricular-subventricular zone.
Unraveling the impact of human cerebrospinal fluid on human neural stem cell fate.
Circulating miRNAs are associated with successful bone regeneration.
Cloned airway basal progenitor cells to repair fibrotic lung through re-epithelialization.
Human fetal lung mesenchymal stem cells ameliorate lung injury in an animal model.
BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress.
AI-based approach to dissect the variability of mouse stem cell-derived embryo models.
Addressing Widening Health Disparities With Inclusive Stem Cell Models.
Other notable FDA approvals, RMATS and status changes
Britecyte’s Adipose Tissue Allograft Earns “Safe to Proceed” Status from FDA.
Bionic Sight’s BS01 Gene Therapy Receives RMAT Designation from the FDA.
Lyla El-Fayomi
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