Updates from the Director of Scientific & Clinical Initiatives
August 2025
You thought the conference special edition was your SCI Spotlight for August? Think again! We have double content this month to showcase some of the main scientific topics of the summer. If you missed the Conference Catch-up Special Edition newsletter last week, you can find that here -Dylan Ritter
LEARN
Infantile Spasms Action Network Workshop
I spent a day in Washington DC with some incredible patient advocates, clinicians, and pharmaceutical representatives representing the Infantile Spasms Action Network. While there, we discussed the critical ways we need to reach the worldwide pediatric community about the dangers of infantile spasms. Infantile spasms (or West syndrome) is a developmental seizure condition that has characteristic movement patterns. Onset is usually around 6 months of age and usually does not appear after 18 months of age. If left untreated, infantile spasms can cause damage to the developing brain, often times without parents even recognizing anything is wrong with their baby. Infantile spasms appear in about 40% of the Dup15q population, but many more infants may have infantile spasms that parents don’t know to recognize.
As one of three organizations on the governance committee, I represented the Dup15q Alliance in discussions surrounding improving awareness for infantile spasms, ensuring our message would reach all members of the community. Primary target audience focuses included those without ready access to high-quality medical care, non-English speakers, and upcoming medical students planning to pursue pediatrics. Every December, we promote Infantile Spasms Awareness Week, a campaign meant to educate new parents, caregivers, and pediatricians about the warning signs of infantile spasms. I encourage all families with a Duper under the age of 2 to visit https://infantilespasms.org/ and learn the warning signs!
If you See signs that your child may have infantile spasms, Take a video, Obtain a diagnosis from your doctor, and Prioritize treatments to prevent developmental delay. STOP Infantile Spasms!
TREAT
What is a Clinical Trial?
A clinical trial is a standardized research study to determine the safety and efficacy of a medical intervention for a specific condition. Clinical trials can only begin when sufficient evidence of medical safety and efficacy for a drug have been shown in “preclinical models” (think animal models like mice or rats). Additionally, strict inclusion criteria are needed to identify the patient population that is suitable for the clinical trial. Common inclusion criteria include genetic diagnosis, age, symptoms, and lack of current medications that could interfere with the new drug being tested.
The early phases of clinical trials incorporate multiple doses of a study drug and heavy scrutiny to ensure that patients are not seeing any unexpected adverse effects from the drug. If the early phase of a clinical trial sees improvements in a specific measure (and the drug appears safe), then the trial is a success and can proceed to the next phase.
Later phases of a clinical trial may have expanded inclusion criteria, like including younger and/or older individuals in the trial. Again, safety and efficacy are both of utmost importance, and participants are closely monitored to ensure there are no negative effects. If a patient has an adverse reaction caused by the clinical trial drug, they will be removed from the clinical trial and monitored to ensure safety.
Clinical trial success is determined by many factors. Some factors, like the drug itself, are not something we as the Dup15q community can control. However, factors like trial enrollment and natural history study participation are both extremely important factors that families can influence. If families participate in ongoing research and natural history studies, drug developers can be more confident that they will be able to have sufficient enrollment in a clinical trial to see real results over a large enough sample size. If families do not support current research efforts, drug companies may be hesitant to prioritize Dup15q clinical trials until enough evidence is gathered that Dup15q syndrome is a worthwhile disorder to treat.
CURE
ASOs and the BBB
ASOs have many molecular complexities that help them function very well for their given purpose (see previous SCI Spotlights for more background). However, the components of an ASO that help it function so well also prevent ASOs from being taken like you would take many common medications. When you take a medication as a pill, that pill is digested in your stomach, and the medicinal molecule is released into the blood stream. If the medicine has specific qualities, it may pass from the bloodstream into the brain to affect brain activity.
If you took an ASO as a pill, the ASO would be easily digested by your stomach acid and would no longer function after being consumed. If an ASO was injected into the bloodstream through an IV injection to bypass stomach digestion, that ASO would still need to cross the blood-brain barrier to reach the brain.
The blood-brain barrier is a layer of highly specialized cells that determine if a chemical is acceptable to pass into the brain from the bloodstream. The integrity of the blood-brain barrier is extremely important to keep your brain safe and protected from pathogens and many other dangers within your body. However, it does make drug development trickier for helping a drug reach the brain.
One factor to determine if a molecule crosses the blood-brain barrier is size. ASOs are very large molecules, which makes them difficult to get across the blood-brain barrier. ASOs can weigh up to 10,000 g/mol, a unit used for measuring chemical size. If you compare that to caffeine (194 g/mol) or alcohol (46 g/mol) that readily cross the blood-brain barrier, you can tell that ASOs are many times larger molecules than some common chemicals.
In a future SCI Spotlight, I will be discussing more about how researchers and clinicians help an ASO reach the brain. Stay tuned!
