In many cases, treating an illness is relatively straightforward: visit a doctor, get a diagnosis, and start targeted treatments. For the most part, we’ve all been involved in this process throughout our lives, for everything from viral infections to burst appendixes.

But when you or your loved one has a rare disease, the process of navigating treatment is much more uncertain. Over 10,000 rare diseases exist today. And they’re more common than you might think. In fact, an estimated 1 in every 10 people globally has a rare disease. Yet the diagnostic journey is often long and arduous, taking years or sometimes decades, and 95% of rare diseases still lack an approved treatment. 

SYNGAP1-related disorders are part of this group. Despite the SynGAP protein’s discovery in 1998, and its subsequent link to intellectual disability and neurodevelopmental conditions in 2009, no therapeutic interventions exist. That means families have faced 27 years of symptom management at this point. And that’s exactly what CAMP4 Therapeutics, a clinical-stage biopharmaceutical company, is hoping to change. 

Recently, Rareatives sat down with CAMP4 Therapeutics’ Chief Medical Officer Dr. Yuri Maricich, MD to discuss the company’s novel approach to designing antisense oligonucleotides (ASOs), an RNA-targeting medicine to increase gene expression; their goals for CMP-002 and its applicability for SYNGAP1-related disorders; and the potential clinical trial the company hopes to launch this year.

What are SYNGAP1-Related Disorders?

Before we dive into CAMP4 Therapeutics, let’s first lay out exactly what SYNGAP1-related disorders are. Sometimes referred to as just SYNGAP1, these disorders are ultra-rare genetic conditions caused by SYNGAP1 gene mutations. The mutations usually occur de novo, or spontaneously, meaning SYNGAP1-related disorders are not typically inherited. People who develop these disorders usually only have one working SYNGAP1 gene, while the other does not work. 

“This is called haploinsufficiency,” Maricich explains.

Normally, our bodies make the SynGAP protein, which regulates neuronal signaling and brain development. In SYNGAP1-related disorders, the mutation stops the creation of SynGAP protein. Without enough protein, abnormal development occurs.

“SYNGAP1 is considered a developmental epileptic encephalopathy,” says Maricich. “It’s a developmental disorder with seizures. But the challenge for families is that SYNGAP1 basically impacts all sorts of bodily processes. Some families struggle with seizures, others with sleep. Some patients have behavioral issues.” 

Maricich is right. SYNGAP1 is extremely variable. An estimated 85% of people with SYNGAP1-related disorders develop difficult-to-control or drug-resistant epilepsy starting by ages 2-3. But the frequency, severity, and types of seizures may differ. Seizures associated with SYNGAP1 include: 

• Absence seizures (with or without eyelid myoclonia) 
• Myoclonic seizures
• Atonic seizures 
• Tonic-clonic seizures

Additional symptoms or manifestations of SYNGAP1-related disorders can include: 

• Hypotonia (low muscle tone)
• Intellectual disability – “100% of individuals with SYNGAP1,” says Maricich 
• Speech delays 
• Dyspraxia / developmental coordination disorder 
• Difficulty sleeping
• Global developmental delay
• Sensory processing disorders
• Gross and/or fine motor skill delays
• Strabismus (crossed eyes) 
• Feeding issues
• High pain threshold 
• Autism
• Behavioral issues 

It is estimated that at least 10,000 people have SYNGAP1-related disorder across the U.S. and Europe. A registry has had 1,806 known patients register worldwide. Maricich expects the number of identified patients to grow as awareness of a potential treatment spreads. Many children are diagnosed with autism or epilepsy and never gain access to more comprehensive genetic testing that would reveal SYNGAP1 as the underlying cause, in part because the condition is still unfamiliar to most physicians.

The condition is “probably undiagnosed substantially,” says Maricich, “and we’d likely contribute to broader identification when starting trials.”

The Journey to CAMP4

When he first began his career, Maricich himself was not fully aware of SYNGAP1 or its impact on families. However, as an internal medicine physician, he did get the opportunity to better understand the patient perspective. In the earlier stages of his career, he worked most closely with acute patients in the hospital and intensive care unit (ICU), and was introduced to both rare and common illnesses.

“As a physician-scientist, I quickly felt frustrated when I met patients and families who didn’t have treatments or the tools to address their conditions,” he explains. “It was hard to see these devastated families and clinicians who wanted to help, but didn’t have any resources available to them.” 

His desire to address this gap propelled Maricich into the drug development space. Throughout the course of his career, Maricich has developed therapeutics at companies including Corixa, Cavion, Xdynia, and Pear Therapeutics, where he helped bring several treatments to market, including Somryst for chronic insomnia, before joining the team at CAMP4 Therapeutics. 

CAMP4’s Work

10 years ago, CAMP4 Therapeutics was founded with a mission. According to Maricich, “CAMP4 was originally based on pioneering work that came out of the Whitehead Institute and the lab of Rick Young.” 

The research helped uncover a class of molecules called regulatory RNA, or regRNA. Initially, says Maricich, “These non-coding species of RNA weren’t thought to be important, necessarily. But more research showed that regRNAs regulate the level of transcription, or the amount of protein from a given gene.” 

He adds that regRNA has two specific attributes. First, the regRNA regions have a 1:1 relationship with a given gene. Essentially, Maricich says, “There’s built-in specificity. When working with regRNA, you are only targeting the gene it’s associated with.” 

Secondly, regRNAs can be targeted to increase gene expression within a specific physiological range, making targeting regRNAs potentially safer than gene therapies. As Maricich explains, “If you modify the level of regRNA, you might see a two-fold increase in protein. But you won’t see a five-, ten-, or hundred-fold increase like in gene therapy. We have not observed a risk of having too much protein.” 

The company then decided to focus on developing antisense oligonucleotide (ASO) therapies for haploinsufficient diseases, as they felt addressing haploinsufficiency was the best and closest fit for CAMP4’s RAP Platform technology. In addition, says Maricich, “Many companies focus on diseases where too much protein is made, so the therapies focus on downregulation. We wanted to focus on upregulation. And since the brain might have more haploinsufficient diseases than any other area of the body, we chose to start there.” 

Why ASOs vs. Other Therapeutic Approaches?

There are several reasons why CAMP4 Therapeutics saw ASOs as an attractive option. First, ASOs are not a new modality. In spinal muscular atrophy (SMA), for example, an ASO therapy called Spinraza has been used to treat over 14,000 patients. As Maricich reinforces, this not only makes physicians and patients more comfortable, but highlights an established safety record.

“The ability to map cell lines, then use our technology to develop targeted ASOs for regRNAs, means we don’t have to do risky new chemistry. We can take established chemistry and bring that forward,” says Maricich. 

Focusing on SYNGAP1

Prior to getting involved in the SYNGAP1-related disorders space, CAMP4 Therapeutics had done work on urea cycle disorders, including a Phase 1 safety study for its therapy CMP-001. However, with a goal of getting more involved in haploinsufficient disorders, CAMP4 Therapeutics began attending conferences.

“And that’s where the patient community brought SYNGAP1 directly to us,” says Maricich. He recalls how one of CAMP4’s scientists heard Mike Graglia, the Founder and CEO of CURE SYNGAP1, speak at the conference and was immediately captivated by his stories. When the scientist went to talk with Graglia, Graglia immediately offered up SYNGAP1 cell lines. 

“Before our scientist landed back in Boston, there were cell lines in the mail to us,” Maricich adds. 

Graglia and his wife, Ashley Evans, founded CURE SYNGAP1, formerly known as the SynGAP Research Fund, in 2018 after their son was diagnosed with SYNGAP1. In the years since, the family-led nonprofit has grown into one of the largest funders of SYNGAP1 research, committing more than $8 million in grants.

Maricich and his team began looking into SYNGAP1 after receiving the cell lines — “the more we learned, the more we understood how completely devastating it can be for families,” he tells me — but the framework for SYNGAP1 research had already been built by CURE SYNGAP1. 

“When we started mapping to see if we could target regRNAs, the SYNGAP1 community had the cell lines ready, had developed an animal model, and had a natural history study running,” Maricich says. “For some organizations, it can take years or even decades to get together the scientific groundwork to begin working on a therapy. Thanks to the work of CURE SYNGAP1, we went from ‘let’s study SYNGAP1’ to ‘ready to go to clinical trial’ in less than three years.” 

CAMP4 has kept that partnership close ever since, keeping patient-centricity as a key part of the mission. Maricich and his team recognize that patients and parents are the experts on their conditions. So they’ve created a bi-directional line of communication. Maricich says, “The whole community is incredible. These patients and families are so dedicated to the cause and will not give up, and it makes us want to work even harder for them. As we’ve started to develop our plans, we’ve shared and solicited feedback directly on the protocol. What are the endpoints of the trial that focus on the aspects of the disease most important to families? We also try to ask how we can support families through the drug development process. We reinforce what they’re already doing that they need to keep doing, like raising awareness, educating others, and supporting natural history studies.”

Here, Maricich pauses. Then he muses, “Natural history studies are such an impactful way to get data into the hands of scientists and work towards both drug development and getting therapies into trial. Oncology has a strong mantra of getting every person into a trial or study of some kind. I would love to see that same approach across rare disease patient communities, but we need to figure out how we can do that as seamlessly as possible so it’s not burdensome for families. Because the more we can dive into research, the more patients we can identify, and the more we can provide them with resources.” 

CMP-002: An Overview

Using its proprietary RAP Platform, as well as the cell lines provided by Graglia, CAMP4 Therapeutics developed CMP-002. The company found a regRNA that controls expression of the SYNGAP1 protein that actually binds to a repressor. 

“CMP-002 binds to the regRNA sequence, and causes a structural change that prevents the repressor from binding,” explains Maricich. “The brakes come off the transcriptional system, allowing for more protein to be made. What’s elegant about this approach is we’re at the stage of transcription where we can tell the healthy allele to make more protein. So, rather than addressing the mutated gene copy, the healthy version does double duty.” 

Maricich also stresses that CMP-002 is a potentially disease-modifying approach, designed to resolve the underlying cause rather than simply address symptoms. 

Before a drug ever reaches a human trial participant, the therapy must prove itself across several different systems. In both the discovery phase and preclinical studies, CAMP4 Therapeutics has found that when treated with CMP-002, SYNGAP1 cell lines, with sibling cell lines as controls, increased SynGAP protein up to or greater than wild type levels. 

In haploinsufficient mice models with fully humanized SYNGAP1, CMP-002 rescued the phenotype. “Essentially, compared to untreated mice, we improved function across cognition, anxiety, and motor back to normal,” says Maricich. Later data also shared that CMP-002 decreased seizure frequency and increased seizure threshold in mice. This is especially profound as people with SYNGAP1 may experience dozens or even a hundred or more seizures each day. 

Finally, studies of CMP-002 in monkey models increased SynGAP protein in relevant brain regions. 

Preparing for a Future Phase 1/2 Trial

At the time of our conversation, CAMP4 Therapeutics had filed its first Regulatory Submission in Australia. On July 27, 2026, the company received approval to begin a first-in-human clinical trial of CMP-002. With the clinical trial starting in Q4 2026, this represents a huge milestone for both CAMP4 Therapeutics and the SYNGAP1 patient community. 

“This is the first potential therapy for SYNGAP1, so we’re humble,” says Maricich. “We recognize that there are many things about this disease that we don’t know and the patient community doesn’t know, which is why we are so excited to work together.” 

CAMP4 Therapeutics hopes to make the CMP-002 trial a global trial to provide access to families across the globe. The focus is looking at safety data, determining the most appropriate dose for subsequent trials, and identifying additional populations.

“For patients and families, this cannot come fast enough,” says Maricich. “I’ve talked to families, had dinner with them, met their children, and gotten to know them better. That is my motivation and what motivates my team. We have a personal responsibility to develop a therapy, and being on the cusp of this trial is incredible. Families have said they never thought this day would come.” 

As the company prepares for the trial, Maricich also notes that families should begin their own preparation. Trials can bring up a lot of unexpected emotions, as participants are fundamentally navigating many unknowns. 

“It’s important for patient communities to talk to each other and learn from each other’s experiences,” Maricich says. “I’ve been encouraging the families to talk to other communities where there have been clinical trials to gain realistic expectations of what trial participation is like.” 

Future Hopes

Maricich also hopes that, in the future, there might be more open-minded or flexible models for trial development. In the rare disease community, some patient populations are exceptionally small or scattered. Others over-focus on certain endpoints, or have patients who are too vulnerable to participate.

“We want to be patient-first, yes. We want to know what’s important for regulators, yes. But we need to be open-minded about rare diseases. We need to bring patient communities together with regulators, working together towards more flexible models. Not every endpoint is right for every patient. How do we develop trials where we promote confidence in the data without oversimplifying very complicated diseases into a single endpoint that is one-size-fits-all?” 

Family Advice

As much as CAMP4 Therapeutics is pushing for a cure, Maricich also wants to ensure the SYNGAP1 community feels supported and empowered. He leans back on his physician training to offer advice to parents on how to navigate an often complicated medical environment. 

“First, determine if you’re working with physicians and healthcare teams who listen. Because for rare diseases, it’s likely that the person you’re talking to is hearing about this disease for the first time. Even experts themselves became experts because they listened and are continuing to learn. If you have the sense you’re not being listened to, you probably need another team,” he stresses. “And look for people who are humble. Are your doctors willing to share when they don’t know something? Are they committed to tracking down the answers? Are they candid? That’s what you need.” 

Beyond that, he encourages parents to be advocates. He recognizes that speaking up can be difficult at times, or uncomfortable, especially if you’re still early on in your rare disease journey. “Families sometimes wonder if they’re being too pushy,” he says. “But you’re the expert on your child. Push for answers. Push your doctors to look at something you feel is worth considering. It’s because of that advocacy that we see so much progress now.” 

About CAMP4 Therapeutics

CAMP4 is developing disease-modifying treatments for a broad range of genetic diseases where amplifying healthy protein may offer therapeutic benefits. The approach amplifies mRNA by harnessing a fundamental mechanism of how genes are controlled. To amplify mRNA, its therapeutic ASO drug candidates target regulatory RNAs (regRNAs), which act locally on transcription factors and are the master regulators of gene expression. CAMP4’s proprietary RAP Platform™ enables the mapping of regRNAs and generation of therapeutic candidates designed to target the regRNAs associated with genes underlying haploinsufficient and recessive partial loss-of-function disorders, of which there are more than 1,200, in which a modest increase in protein expression may have the potential to be clinically meaningful. 

Learn more at camp4tx.com, or follow CAMP4 Therapeutics on LinkedIn and X.