Peter is the Director of Development at SRF and also a SYNGAP1 dad. He’s dedicated to finding a cure and is doing his part to raise funds towards the needed research. He hopes this article can help with conversations around this question that often comes up.
All humans are made up of about 20,000 different genes. A person has two copies of each gene: one inherited from mom, one from dad. Genes contain the instructions required for healthy development and pass on our inherited characteristics (blue eyes, red hair, blood type O+).
SYNGAP1 is one of those genes and is responsible for production of the protein SynGAP, necessary for proper brain function and development. Patients with a SYNGAP1 disorder have a mutation in one of the copies of their SYNGAP1 gene that causes an insufficiency of the SynGAP protein.
In almost all cases, this mutation didn’t come from either parent but is what is known as de novo, or new. In fact, all people contain a number of de novo mutations. But while some variants result in only minor edits that don’t change a gene’s function, other variants are significant and can be disease-causing. This is the case with a SYNGAP1 variant.
Patients with a SYNGAP1 disorder only have one working copy of the SYNGAP1 gene, so they are only capable of creating about 50% of the critical SynGAP protein. This deficiency causes the symptoms that we see in our children: intellectual disability, drug-resistant epilepsy, autism, hypotonia (muscle weakness), very limited speech (mostly non-verbal), and severe behaviors (impulsivity & aggression).
Today, best practice is to treat each symptom separately via various combinations of drugs and therapies (PT, OT, speech, behavioral therapy, etc.). As a result, our kids are often over-drugged and suffer from associated side effects (e.g., behaviors, or health concerns such as elevated liver enzymes). The currently available drug regimen is inconsistent, unreliable, and insufficient in helping our kids. It’s a band-aid to address symptoms, but it does not fix the core problem - SynGAP deficiency.
What if we could identify a treatment--either a repurposed drug or a novel therapy--capable of expressing extra SynGAP protein from the working copy of the gene? Theoretically this would compensate for the non-functional copy. To do this, we have to look into new and emerging scientific strategies and techniques, which is what we are working so hard to fund. Research in animal models tells us that we can expect such a therapy to be capable of rescuing the complete phenotype, in other words, restoring proper brain function, resolving seizures, reducing autistic and aggressive behaviors, and improving muscle tone and speech.
It sounds like science fiction, but these therapies are already here for other conditions of the central nervous system. For example, Spinraza is a medication that treats the underlying cause, not just the symptoms, of Spinal Muscular Atrophy (SMA). Further, Dravet Syndrome, which is very similar to SYNGAP1, has a type of treatment called an ASO currently in clinical trials. Building on SRF's very first grant, Dr. Huganir of the SRF Scientific Advisory Board (SAB) has a grant from SFARI to use an ASO for SYNGAP1. Plus, Drs Prosser & Heller, both also on our SAB, are working on yet another ASO for SYNGAP1. The future is coming fast.
The earlier in life that we can deliver these treatments to our children, the better their prognosis. It’s not wild to think that in the not-so-distant future SYNGAP1 could be included in prenatal screens, and patients could begin receiving treatments shortly after birth, or perhaps even in utero. Such a treatment could be considered curative. These children deserve a cure and our children, here today, deserve a treatment that will restore as much of their brain function as possible.
Please help us accelerate this meaningful work by donating today: syngapresearchfund.org/donate.
About Syngap Research Fund
SRF, incorporated in 2018, is a 501(c)(3) public charity. The mission is to improve the quality of life of SYNGAP1 patients through the research and development of treatments, therapies and support systems. Completely parent-led, SRF is the largest non-government funder of SynGAP research having committed over $1.5M in grants. The founders cover all operational costs, allowing 100% of donations to go to research. SRF is a member of the Personalized Medicine Coalition, COMBINEDbrain, Global Genes Foundation Alliance and Genetic Alliance UK. For more information, visit SyngapResearchFund.org.