By Holly Alyssa MacCormick
Some of the biggest advances in autism research have come from a unique and dedicated group—the families and patient advocates who live with autism every day.
Matthew State, MD, PhD, chief scientific advisor for the Aligning Research to Impact Autism (ARIA) initiative and chair of psychiatry and behavioral sciences at the University of California, San Francisco (UCSF), has worked alongside patient advocates including Allyson Berent and Alison Singer for years.
Insights from advocates
For the California Institute for Regenerative Medicine (CIRM), State serves as a research advisor for grants led by UCSF neuroscientist Tomasz Nowakowski. These grants are part of CIRM’s ReMind initiative, which funds collaborative, multi-investigator projects that have the potential to help researchers make discoveries faster than if each investigator and research team worked independently.
“While CIRM has funded neuroscience discovery research in the past, the ReMIND program is the largest investment CIRM has made to date in neuropsychiatric disorders,” said Chan Tan, a senior science officer for CIRM’s Discovery & Education programs. “In addition, ReMIND represents a pilot program for integrated, multidisciplinary awards. CIRM’s future funding cycles expand on this design to fund additional areas of research including neurological diseases like Alzheimer’s disease.”
State uses insights from patient advocates and his expertise as a child and adolescent psychiatrist and geneticist to help Nowakowski’s team identify the genes likely to have the greatest impact for patients with schizophrenia, profound autism, and other severe neurodevelopmental disorders.
“Many psychiatric disorders are due to a conspiracy of hundreds or thousands of changes in the genome,” said State. “But there’s a minority—an important minority—of patients across multiple psychiatric disorders who have what they have because of a single identifiable change in their genome.”
State’s strategy to focus on single genes with outsized effects is based on observations he made as a child psychiatrist. He found that identifying rare changes in the genome that are present in many psychiatric disorders provides a more direct understanding of the biology than searching for patterns in a sea of genes with overlapping effects.
“There are many reasons why people study genetics, including to understand population risk and a variety of other things,” said State. “I was driven by the children that I was seeing, many who ultimately now have been revealed to have genetic abnormalities that are identifiable. And so, I became focused on trying to find genes where a single change in the genome was having a very significant effect on a patient, and by extension, their family.”
Connecting with patient advocates
Communicating with patient advocates and families affected by autism helps State identify which of the more than 200 ‘autism’ genes research should focus on.
“The diagnosis [for autism] is so broad, it goes from people who require 24-hour care and don’t have useful language, to folks who do not experience the diagnosis as a disability,” said State. “So if you start talking about autism as one thing, you pull in an incredible range of human experience and very diverse perspectives on what’s helpful and what’s useful to families and the community. Focusing on Profound ASD [autism spectrum disorder] has helped align our scientific efforts with what is of greatest importance to those families and that community.”
The CIRM-funded research described here focuses on profound autism, which is defined here as severe intellectual challenges, minimal or absent speech, and the need for 24-hour care. For people with profound autism, the impact on human health is significant, and potential therapies aim to alleviate these harmful symptoms.
“Severe neuropsychiatric disorders such as profound autism are difficult to predict, manage, and often require lifelong medical support,” said Nowakowski. “These disorders significantly impact patients in their families, are a major source of socioeconomic burden in California, and urgently need progress in novel therapeutic development.”
Ensuring that the research reflects the needs of patients and their families is one of the reasons why Nowakowski sought out State as an advisor for the study.
“None of this happens without their help,” said State. “Family groups and patient organizations are absolutely central to research.”
From parent to patient advocate
Patient advocates are often ordinary people called to take extraordinary action when a family member is diagnosed with a disease or condition. Their expertise in disease is hard-won from their lived experiences, and their dedication is unshakable. Their diverse backgrounds bring fresh perspectives to research.
That’s why CIRM includes several patient advocates as members of the board, known as the Independent Citizens’ Oversight Committee (ICOC), a diverse group of up to 35 California-based patient advocates, nurses, research leaders, and biotechnology industry leaders. The ICOC makes all decisions regarding CIRM’s operations and funding, including deciding which research to support.
Berent, who has worked with State since 2021, is a veterinary internal medicine specialist and interventional radiologist. In 2014, her daughter was diagnosed with the rare genetic disorder called Angelman syndrome, which causes severe developmental delay and communication challenges in young children. This prompted her to broaden her career and apply her knowledge from animal research to human research as chief science officer for the Foundation for Angelman Syndrome Therapeutics (FAST). She is now also chief development officer for AS2Bio, a drug-development accelerator that advances genetic therapies for Angelman syndrome to first-in-human clinical trials.
“I’m a veterinary clinician-scientist by training, but I became a drug developer by necessity as my entire career has been in medical device development,” said Berent. “My daughter lives with Angelman syndrome, and like every parent, I wanted to give her, and thousands of others, the chance for a better future. When no therapies existed, I realized that if I wanted to change the trajectory of her life, I couldn’t just hope someone else would do it—I had to help build the path. Parents don’t choose this work because they want to. They choose it because their children deserve more than waiting for someone else to.”
Berent’s extensive research portfolio includes two CIRM-funded grants to develop possible gene therapies; one a stem cell gene replacement therapy for Angelman syndrome, and the other a gene replacement therapy focused on Pitt Hopkins Syndrome.
“Too often, parents of children with rare diseases are seen through the lens of their desperation rather than their determination,” Berent said. “People assume that because you’re a mother, your passion can’t coexist with scientific rigor or meaningful contributions to drug development. Dr. State never saw us (FAST) that way.”
He recognized parents as partners, she said.
“He’s a brilliant clinician-scientist, but what truly sets him apart is that he sees beyond the gene and beyond the diagnosis,” Berent said. “He understands the people and families behind the disease and has an extraordinary ability to bring together compassion and scientific excellence. From the very beginning, he treated me—and our community—with genuine respect, as equal partners in the mission to develop transformative therapies, and a model for an accelerator that could not only serve Angelman syndrome but many other neurodevelopmental disorders.”
A scientific compass
Some patient advocates, like Berent, have training in the sciences, but many patient advocates have expertise in other fields and that’s part of their superpower. Their diverse backgrounds bring fresh perspectives to research.
Alison Singer’s older brother has autism, so she was already familiar with it when her daughter was diagnosed with autism in 2001. At the time, she was a vice president at NBC with a B.A. in economics from Yale and an MBA from Harvard. Her daughter’s diagnosis prompted her to switch from TV news to professional advocacy, and in 2005 she left NBC to join Autism Speaks as its first CEO.
In 2009, Singer co-founded and became president of the Autism Science Foundation (ASF) to help advance and fund autism research. State, who was (then) co-founder and co-director of the Yale Program on Neurogenetics, became the first chair of ASF’s Scientific Advisory Board, which was tasked with funding research on the biology and causes of autism.
“It was actually quite revolutionary at the time because there was this [belief that] … you’ll never understand what causes autism … there’s no genetic component,” said Singer. “That turned out to be completely wrong. And one of the people who did the science to help us understand how wrong that was was Matt.”
“He serves as our scientific compass,” said Singer. “We really rely on his depth of knowledge and his incredible expertise to guide us in the projects that we choose to fund.”
The impact of patient advocates
In addition to leading and forming organizations dedicated to autism research, Berent and Singer have recruited patients for scientific studies, organized research symposia, expanded our knowledge of autism, helped fund autism research, and, in some cases, started companies to develop genetic therapies.
Their work with State is a win-win alliance.
To speed therapies for Angelman syndrome, Berent gathers global experts each year to identify knowledge gaps. She soon met parents facing similarly severe disorders who wanted genetic therapies but didn’t know how to begin.
“The secret sauce to our relationship is that we are both very candid,” said Singer. “He’s candid with me about the science that’s likely to move the field forward. I’m candid with him about what families are looking for regarding research and making sure that the research is grounded in the real lives of real people.”
To fast-track the development of therapies for Angelman syndrome, each year Berent convenes a diverse group of experts in neurodevelopmental diseases from around the world to identify knowledge gaps related to the condition. In the process, Berent met parents of children affected by many similarly severe neurodevelopmental disorders who also wanted to develop genetic therapies for their loved ones but didn’t know where to start.
“I started receiving phone calls from parent groups around the world, saying: ‘How do we do what you did?’” said Berent.
In response, FAST and the Simons Foundation Autism Research Initiative formed the International Angelman Syndrome Research Council to streamline, advance, and share the research and drug development process for Angelman syndrome and other neurodevelopmental disorders. The primary goal of the council is to advance drug development for neurodevelopmental disorders and to help other groups learn from and benefit from FAST’s expertise.
Berent’s experience also helps researchers like State, who want to learn more about the nuances of drug development for these severe neurodevelopmental disorders.
“When Dr. State became chief scientific advisor for the ARIA initiative, he asked me to help design an infrastructure modeled on FAST’s roadmap—a patient-led framework that had already demonstrated how to accelerate genetic therapies for a rare monogenic neurodevelopmental disorder,” said Berent. “The fact that FAST’s approach became the blueprint for a broader effort in monogenic autism was incredibly meaningful. Working alongside him to help shape that vision and translate what we had learned into a scalable model for other genetic disorders was truly inspiring.”
Shining a light on profound autism
Autism research rarely included people with profound autism, but that is changing. Work by State, Nowakowski, Berent, and Singer is driving this shift.
Singer said Matt is unusual among scientists. She noted that many studies focus on high‑functioning participants because they are easier to work with. Matt chose to study profound autism—children with very low IQ, minimal speech, seizures, and constant supervision needs. These medically complex children have long been left behind in research. She said Matt focuses on them because their needs are greatest.
These studies also help reduce the stigma around profound autism.
State said CIRM’s work, even without immediate therapies, has eased much of the stigma families face. He added that progress by Nowakowski and others changes what it means to be a parent of a child with severe neurodevelopmental disabilities.