Can Genetic Testing Help Shed Light on the Autism Epidemic?
Autism cases are still on the rise, and scientists don't know why. In April, the Centers for Disease Control (CDC) reported that rates of autism had increased once again, now at an estimated 1 in 59 children up from 1 in 68 just two years ago. Rates have been climbing steadily since 2007 when the CDC initially estimated that 1 in 150 children were on the autism spectrum.
Some clinicians are concerned that the creeping expansion of autism is causing the diagnosis to lose its meaning.
The standard explanation for this increase has been the expansion of the definition of autism to include milder forms like Asperger's, as well as a heightened awareness of the condition that has improved screening efforts. For example, the most recent jump is attributed to children in minority communities being diagnosed who might have previously gone under the radar. In addition, more federally funded resources are available to children with autism than other types of developmental disorders, which may prompt families or physicians to push harder for a diagnosis.
Some clinicians are concerned that the creeping expansion of autism is causing the diagnosis to lose its meaning. William Graf, a pediatric neurologist at Connecticut Children's Medical Center, says that when a nurse tells him that a new patient has a history of autism, the term is no longer a useful description. "Even though I know this topic extremely well, I cannot picture the child anymore," he says. "Use the words mild, moderate, or severe. Just give me a couple more clues, because when you say autism today, I have no idea what people are talking about anymore."
Genetic testing has emerged as one potential way to remedy the overly broad label by narrowing down a heterogeneous diagnosis to a specific genetic disorder. According to Suma Shankar, a medical geneticist at the University of California, Davis, up to 60 percent of autism cases could be attributed to underlying genetic causes. Common examples include Fragile X Syndrome or Rett Syndrome—neurodevelopmental disorders that are caused by mutations in individual genes and are behaviorally classified as autism.
With more than 500 different mutations associated with autism, very few additional diagnoses provide meaningful information.
Having a genetic diagnosis in addition to an autism diagnosis can help families in several ways, says Shankar. Knowing the genetic origin can alert families to other potential health problems that are linked to the mutation, such as heart defects or problems with the immune system. It may also help clinicians provide more targeted behavioral therapies and could one day lead to the development of drug treatments for underlying neurochemical abnormalities. "It will pave the way to begin to tease out treatments," Shankar says.
When a doctor diagnoses a child as having a specific genetic condition, the label of autism is still kept because it is more well-known and gives the child access to more state-funded resources. Children can thus be diagnosed with multiple conditions: autism spectrum disorder and their specific gene mutation. However, with more than 500 different mutations associated with autism, very few additional diagnoses provide meaningful information. What's more, the presence or absence of a mutation doesn't necessarily indicate whether the child is on the mild or severe end of the autism spectrum.
Because of this, Graf doubts that genetic classifications are really that useful. He tells the story of a boy with epilepsy and severe intellectual disabilities who was diagnosed with autism as a young child. Years later, Graf ordered genetic testing for the boy and discovered that he had a mutation in the gene SYNGAP1. However, this knowledge didn't change the boy's autism status. "That diagnosis [SYNGAP1] turns out to be very specific for him, but it will never be a household name. Biologically it's good to know, and now it's all over his chart. But on a societal level he still needs this catch-all label [of autism]," Graf says.
"It gives some information, but to what degree does that change treatment or prognosis?"
Jennifer Singh, a sociologist at Georgia Tech who wrote the book Multiple Autisms: Spectrums of Advocacy and Genomic Science, agrees. "I don't know that the knowledge gained from just having a gene that's linked to autism," is that beneficial, she says. "It gives some information, but to what degree does that change treatment or prognosis? Because at the end of the day you have to address the issues that are at hand, whatever they might be."
As more children are diagnosed with autism, knowledge of the underlying genetic mutation causing the condition could help families better understand the diagnosis and anticipate their child's developmental trajectory. However, for the vast majority, an additional label provides little clarity or consolation.
Instead of spending money on genetic screens, Singh thinks the resources would be better used on additional services for people who don't have access to behavioral, speech, or occupational therapy. "Things that are really going to matter for this child in their future," she says.
Its strength is in its lack of size.
Using materials on the minuscule scale of nanometers (billionths of a meter), nanomedicines have the ability to provide treatment more precise than any other form of medicine. Under optimal circumstances, they can target specific cells and perform feats like altering the expression of proteins in tumors so that the tumors shrink.
Another appealing concept about nanomedicine is that treatment on a nano-scale, which is smaller yet than individual cells, can greatly decrease exposure to parts of the body outside the target area, thereby mitigating side effects.
But this young field's huge potential has met with an ongoing obstacle: the recipient's immune system tends to regard incoming nanomedicines as a threat and launches a complement protein attack. These complement proteins, which act together through a wave of reactions to get rid of troubling microorganisms, have had more than 500 million years to refine their craft, so they are highly effective.
Seeking to overcome a half-billion-year disadvantage, nanomaterials engineers have tried such strategies as creating so-called stealth nanoparticles.
“All new technologies face technical barriers, and it is the job of innovators to engineer solutions to them,” Brenner says.
Despite these clever attempts, nanomedicines largely keep failing to arrive at their intended destinations. According to the most comprehensive meta-analysis of nanomedicines in oncology, fewer than 1 percent of nanoparticles manage to reach their targets. The remaining 99-plus percent are expelled to the liver, spleen, or lungs – thereby squandering their therapeutic potential. Though these numbers seem discouraging, systems biologist Jacob Brenner remains undaunted. “All new technologies face technical barriers, and it is the job of innovators to engineer solutions to them,” he says.
Brenner and his fellow researchers at the Perelman School of Medicine at the University of Pennsylvania have recently devised a method that, in a study published in late 2021 involving sepsis-afflicted mice, saw a longer half-life of nanoparticles in the bloodstream. This effect is crucial because “the longer our nanoparticles circulate, the more time they have to reach their target organs,” says Brenner, the study's co-principal investigator. He works as a critical care physician at the Hospital of the University of Pennsylvania, where he also serves as an assistant professor of medicine.
The method used by Brenner's lab involves coating nanoparticles with natural suppressors that safeguard against a complement attack from the recipient's immune system. For this idea, he credits bacteria. “They are so much smarter than us,” he says.
Brenner points out that many species of bacteria have learned to coat themselves in a natural complement suppressor known as Factor H in order to protect against a complement attack.
Humans also have Factor H, along with an additional suppressor called Factor I, both of which flow through our blood. These natural suppressors “are recruited to the surface of our own cells to prevent complement [proteins] from attacking our own cells,” says Brenner.
Coating nanoparticles with a natural suppressor is a “very creative approach that can help tone and improve the activity of nanotechnology medicines inside the body,” says Avi Schroeder, an associate professor at Technion - Israel Institute of Technology, where he also serves as Head of the Targeted Drug Delivery and Personalized Medicine Group.
Schroeder explains that “being able to tone [down] the immune response to nanoparticles enhances their circulation time and improves their targeting capacity to diseased organs inside the body.” He adds how the approach taken by the Penn Med researchers “shows that tailoring the surface of the nanoparticles can help control the interactions the nanoparticles undergo in the body, allowing wider and more accurate therapeutic activity.”
Brenner says he and his research team are “working on the engineering details” to streamline the process. Such improvements could further subdue the complement protein attacks which for decades have proven the bane of nanomedical engineers.
Though these attacks have limited nanomedicine's effectiveness, the field has managed some noteworthy successes, such as the chemotherapy drugs Abraxane and Doxil, the first FDA-approved nanomedicine.
And amid the COVID-19 pandemic, nanomedicines became almost universally relevant with the vast circulation of the Moderna and Pfizer-BioNTech vaccines, both of which consist of lipid nanoparticles. “Without the nanoparticle, the mRNA would not enter the cells effectively and would not carry out the therapeutic goal,” Schroeder explains.
These vaccines, though, are “just the start of the potential transformation that nanomedicine will bring to the world,” says Brenner. He relates how nanomedicine is “joining forces with a number of other technological innovations,” such as cell therapies in which nanoparticles aim to reprogram T-cells to attack cancer.
With a similar degree of optimism, Schroeder says, “We will see further growing impact of nanotechnologies in the clinic, mainly by enabling gene therapy for treating and even curing diseases that were incurable in the past.”
Brenner says that in the next 10 to 15 years, “nanomedicine is likely to impact patients” contending with a “huge diversity” of conditions. “I can't wait to see how it plays out.”
Podcast: A Nasal Spray COVID Booster Shot, With Dr. Akiko Iwasaki
The "Making Sense of Science" podcast features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This monthly podcast is hosted by journalist Kira Peikoff, founding editor of the award-winning science outlet Leaps.org.
Real-world data shows that protection against Covid-19 infection wanes a few months after two or three shots of mRNA vaccines (while protection against severe disease remains high). But what if there was another kind of booster that could shore up the immune response in your nose, the "door" to your body? Like bouncers at a club, a better prepared nasal defense system could stop the virus in its tracks -- mitigating illnesses as well as community spread. Dr. Akiko Iwasaki, an immunologist at Yale, is working on such a booster, with fantastic results recently reported in mice. In this episode, she shares the details of this important work.
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Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.