[Podcast] The Progress Profile: Alzheimer’s Research in Focus

Holla, who completed her PhD in Raman’s lab and is now a postdoctoral researcher studying memory at New York University in New York City, designed and ran experiments in mouse cerebellar slices. She positioned a stimulation electrode on the parallel fibers, the main pathway that excites Purkinje cells, and a recording electrode on the Purkinje cells themselves. She played recordings of the artificial neurons’ waveforms into the tissue through a standard stimulation electrode at four different speeds: 7, 60, 218, and 740 spikes per second. At every speed below 200 spikes per second, the Purkinje cells fired in response. The strongest results came at 60 spikes per second, where each artificial spike lasted 0.7 milliseconds, which is fast enough to trigger the cell but brief enough to avoid flooding the tissue with unnecessary current. Above 200 spikes per second, the cells stopped responding. They simply cannot fire that fast. The team included the 740-spikes-per-second condition on purpose to directly challenge the many engineering groups building artificial neurons that operate at those speeds. “We had to show them [740 spikes] wasn’t sufficient,” Brown said. “You can’t work that fast.” “You can see the living neurons respond to our artificial neuron,” Hersam said. But he is careful to note a caveat: The printed artificial neurons were not touching the brain tissue. The waveforms they generated were recorded and then played back into the slice through standard laboratory stimulation equipment. The next step is to prove the printed device itself can interface with living tissue.

Brown was studying gene therapy in the 1990s when he designed a technology to turn mRNA expression on or off in different cells. For the new mouse study, published in Nature Biotechnology , he adapted the technology to turn off mRNA expression in dendritic cells, muscle cells, or liver cells. The researchers then vaccinated the mice with each version, delivering the vaccines both intravenously and intramuscularly. “The results were pretty stunning,” Brown said. When mRNA expression was turned off in muscle cells, T-cell response went down, suggesting muscle cells play a role in immunity. When expression was turned off in liver cells, T-cell expression tripled — indicating liver cells dampen immunity. Turning off expression in dendritic cells had no effect on T-cell activation, though it did reduce the number of killer T cells by as much as half. (Interestingly, no such reduction occurred when the antigen was SARS-CoV-2 spike. Brown is now investigating why different antigens had varying effects.) Knowing all this is crucial for designing effective mRNA vaccines and therapies. That’s because different mRNA therapies require different strategies. Cancer vaccines must boost tumor-fighting killer (CD8+) T cells. For genetic disease treatments, scientists want to avoid triggering the immune system to prevent killing the very cells the mRNA is meant to modify. “Understanding the immunology is extremely important for this class of drug,” Brown said. The finding doesn’t mean dendritic cells aren’t important for mRNA vaccines to work. “It just means that the mRNA doesn’t have to get into those cells to induce an immune response,” Brown said. Instead, the antigen can be transferred to those dendritic cells.

One of the biggest biotech news stories of recent years is China’s continued rise as a biotech and life sciences powerhouse. China conducts a quarter of all clinical trials and drug development and has almost 1,500 new drugs in development.¹ Many China-based biotechs have benefitted from government funds, out-licencing deals with large pharmas and venture capital funding. However, policymakers in the US and EU have concerns about the possible threat to their region’s biosecurity and competitiveness as centres for health and life science research. Given China’s increased importance, ICON Biotech conducted the same biotech sector survey with 100 China-based biotech leaders. The results show that Chinese biotechs face many of the same challenges as biotechs located elsewhere. They share the same funding challenges and burdens associated with increasingly complex clinical trials and regulations.

With data expected in the fourth quarter of 2026, we are prioritizing histology alongside patient-reported outcomes using the Celiac Disease Symptom Diary, one of only two instruments developed in line with U.S. Food and Drug Administration (FDA) guidance, to capture changes in symptoms such as abdominal pain and nausea. Ultimately, the broader aim is to give gastroenterologists and patients a therapeutic option for a disease that has long been managed without one. The future of drug development will not be defined by statistical significance alone, but by whether new therapies also improve the daily burden of living with celiac disease. “The first therapy to cross the line could change the field,” Geller concluded. “It would help establish celiac as a serious medical condition with options beyond a restrictive diet and open the door for what comes next.” Dr. Paul Lizzul is chief medical officer at First Tracks Biotherapeutics, a clinical ‑ stage biotechnology company advancing antibody therapeutics that modulate immune pathways implicated in autoimmune and inflammatory diseases. Marilyn Geller serves as an advisor to First Tracks Bio. Footnotes Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev . 2014;260(1):221-234. https://doi.org/10.1111/imr.12191. Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci U S A . 2009;106(37):15849-15854. https://doi/full/10.1073/pnas.0908834106. Anthony S, Schluns KS. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation. Research and Reports in Biology . 2015;6:25-37. https://doi.org/10.2147/RRB.S57685.