Part 2: Can the Cell Danger Response Be Reset?
Cell-El researchers are interested in knowing If Autism Spectrum Disorder (ASD) can be detected in the body’s chemistry even before symptoms fully appear, the next question is just as important: can that chemistry be changed?
This is where Dr. Robert Naviaux’s work on the Cell Danger Response, or CDR, becomes especially intriguing. His research suggests that in some individuals with Autism Spectrum Disorder (ASD), cells may remain in a prolonged “alarm mode” (see part 1 of this series – ASD: First Indicators) Instead of returning to a calmer state after a stressor has passed, the body may continue to behave as if danger is still present. This persistent state may affect metabolism, immune signaling, mitochondrial function, gut-brain communication, and neurodevelopment.
One of the key systems involved is purinergic signaling. This signaling system uses molecules such as ATP (Adenosine Triphosphate) to allow cells to communicate, especially during stress or injury. ATP is best known as the energy-carrying molecule inside cells, but when cells are stressed or injured, ATP can also be released outside the cell as a danger signal.
To test this idea, researchers studied suramin, a medication that has been used for more than a century to treat African sleeping sickness. Suramin blocks certain purinergic signaling pathways, making it a useful tool for studying the CDR hypothesis.
In Naviaux’s small 2017 SAT-1 pilot trial, ten boys with ASD participated: five received a single low dose of IV suramin and five received placebo. The children who received suramin showed measurable but temporary improvements in areas including language, social interaction, and repetitive behaviors. The word “temporary” is important: The effects faded as the drug left the body, and the study was far too small to draw broad clinical conclusions.
Boy with autism in a classroom – AI-generated illustration.
A subsequent Phase 2 study that took place during 2019-2021 with PaxMedica, (currently rebranded as Kuvatris Therapeutics Inc.) in South Africa examined repeated low-dose suramin infusions in 52 boys with moderate to severe ASD. The trial found that a 10 mg/kg dose led to significant clinical improvements, while a higher 20 mg/kg dose did not outperform the placebo. Across the study, the treatment was generally well-tolerated, with most side effects reported as mild to moderate.
Research continues to evolve with the STAT-2A trial (NCT06866275), a randomized, double-blind Phase 2 crossover study now in progress. This investigation is assessing the effects of intravenous suramin sodium, referred to as KZ101 (formally PAX101), in a cohort of boys aged 5 to 14 diagnosed with ASD. Unlike other delivery methods, this trial utilizes IV infusions to establish preliminary proof of concept, examining safety, pharmacokinetics, and measurable clinical changes in areas such as socialization.
In a parallel development, Kuvatris Therapeutics Inc. is exploring PAX-102, an intranasal version of the medication. The shift toward intranasal administration is not merely for ease of use; it represents an attempt to target the central nervous system through direct nasal pathways while potentially limiting overall systemic exposure. . It is important to note that this program remains in its early stages, as current published clinical data on human ASD subjects specifically involve the intravenous form rather than the intranasal PAX-102 formulation.
Ultimately, the significance of these developments lies in the broader scientific shift toward understanding the measurable biology of ASD. Researchers are increasingly focused on the complex interplay of mitochondrial health, immune signaling, purinergic pathways, metabolic function, neuroinflammation, and the communication between the gut and the brain.
This is where Cell-El’s work is essential. Because ASD involves measurable biological changes, biomarkers are critical for identifying specific patterns to advance precision medicine. Cell-El uses AI-driven proteomic blood analysis to decode the diverse biological pathways underlying ASD.
Help Us Help You
Better diagnostics for ASD based on laboratory-measured objective biomarkers can possibly enable researchers and clinicians to provide more precise and personalized treatment. You too can make a difference in the lives of children with ASD and their families by joining the Cell-El study. Cell-El is recruiting the following cohorts: High risk infants aged 10-18 months and their mothers; 2-12 year olds who are typically developing, or with autism; 2-18 year olds pre and post Stem Cell Therapy (SCT). Please note: At this time we are only recruiting participants residing in Israel.
Please contact Leah at [email protected] or fill out the form to find out about eligibility to participate in our diagnostic study and please help spread the word about the Cell-El study. Sharing our study will enable our important biomarker diagnostic tool to be integrated into autism treatment as quickly as possible.
Disclaimer: This content is for informational purposes only and does not constitute medical advice or treatment recommendations. Cell-El Therapeutics Ltd. does not endorse any specific therapies mentioned. Always consult a qualified healthcare professional before making medical decisions. Read more
