Nordmoe Family Donation to SRF Launches the SYNGAP1 Missense Fund – PR23

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See official press release here.

Mill Valley, CA – June 18, 2024 SRF has established a dedicated account to support research regarding SYNGAP1 missense variants.  This account is being launched with a $10,000 donation from Dennis and Janet Nordmoe. This is a cause close to their hearts, as their granddaughter Olivia was diagnosed with SYNGAP1-Related Disorder (SRD) caused by a missense variant earlier this year.

Missense Research: Neglected to Date

“Most diagnosed SYNGAP1-Related Disorder (SRD) patients have protein truncating variants (PTV) as opposed to missense variants. Virtually all PTVs are assumed to have the same impact at the molecular level, but each missense is treated as a unique case.  This is because we just don’t understand what is happening well enough.  As a result, the majority of the research, models, and therapies are targeted at PTVs.” explains Mike Graglia, founder of SRF. He continues, “The default setting in industry and academia is that missense variants are a problem to solve in the future. We disagree. Families with missense variants are rightfully concerned that their loved ones may not have timely access to precision medicines currently being developed. The only way to address this is to invest in and support this research through the SynGAP Research Fund 501(c)(3), the leading patient advocacy group working to improve the lives of SRD patients.”  

“SRF has been investing in missense research since 2022, when we partnered with Leon & Friends who were early advocates of missense research. This is a critical area of research as it impacts both our diagnosed patient numbers and access to precision medicines.” says Aaron Harding, Director of Critical Operations, Lead for the SYNGAP1 Missense Patients and father of Jaxon (18). He continues, “To date we have funded over $700,000 of missense research and reagents to improve our understanding of missense variants.” 

Grant$
Courtney$200,000
Courtney 2$110,000
Postilla$100,000
Carvill via MDBR$65,000
InVivo Biosystems$10,000
Missense Line 1 ipsc$11,000
Missense Line 2 ipsc$11,000
Missense Line 3 ipsc$11,000
RB Screen ML 1$105,000
RB Screen ML 2$105,000
$728,000
Table 1: Summary of SRF Grantmaking specifically for missense variant related research to date.

About the Donation

The Nordmoes realize how costly it is to fund impactful research, so their initial donation of $10,000 is the first step. This will fund the creation of an iPSC or induced Pluripotent Stem Cell with SRF’s partner COMBINEDBrain. The iPSC will then reside in the CB/SRF Biobank, available for industry and academic partners to use in their work to develop better therapies for SYNGAP1 missense patients. This process, which takes approximately nine months, is an important step toward a path to a cure, as these cell lines will be used to facilitate research and evaluate therapies. Beyond this, the family will be reaching out to extended family members, friends, and others encouraging donations to SRF’s Missense Fund (Syngap.Fund/MissenseFund), hoping to raise at least $50,000. 

According to Suzanne Jones, SRF Board Chair and parent to a missense SYNGAP1 child, “The entire SYNGAP1 missense community will benefit greatly from the Nordmoe family’s establishment of a Missense Fund. Having a means to specify missense donations within the Fund gives these families a meaningful outlet for their own financial contributions.”

Olivia’s Diagnosis

When the diagnosis of SYNGAP1 was received, Olivia’s mom, Laura Goretski, was thankful to finally have an answer. “When you’re trying to figure out what’s going on, and many of the things the doctors are testing for are life-shortening diseases, it’s pretty scary. When you have an answer, now you know, and you can work on getting somewhere.” Mrs. Goretski adds, “Pre-diagnosis, there’s the thought of, ‘Did I do something wrong to cause this?’ Then with a diagnosis, there’s the thought that the life you pictured them having isn’t going to happen.”

Dennis Nordmoe had many hopes for his granddaughter, “…but the disease won’t go away. It was a punch to the gut that this will be a permanent part of our life unless something is discovered to change it. I just feel that there is so much intelligence locked up in her that cannot be expressed, but functioning intelligence is developed through education and interaction. We need to, as soon as possible, do whatever we can to break through to unlock it.”  

“Thank God that Olivia has the family she has,” was one of the first thoughts Janet Nordmoe had upon hearing her granddaughter’s diagnosis. “She has the most patient, attentive, caring, balanced, and informed parents. She couldn’t do better. Also, her big sister (MaryAnne) has a lot of those qualities as well.”

About Olivia

Olivia was born in 2018, as a big happy baby, and appeared to be completely healthy. She had what turned out to be relatively minor issues, including torticollis, a mild lip tie, and a pseudotumor within the neck muscle. Soon, though, it was noticed that milestones were being missed. Therapies for these ended at 14 months of age, but by the time she was 2, Olivia only had a few words. At age 3, her vocabulary remained limited, so she began speech therapy. Low muscle tone was also a concern. She was diagnosed with Autism Spectrum Disorder (ASD) when she was 4, and genetic testing was performed. SYNGAP1 came back on the panel as a variant of unknown significance (VUS). Additional testing confirmed a pathogenic missense variant diagnosis for SYNGAP1.

Olivia loves speech therapy and uses her communication device to choose words to let others know what she wants. She currently attends half-day kindergarten and therapy sessions for the other half. “I did not know how it was going to go,” says Mrs. Goretski. “At the beginning of the year, she wasn’t talking very much. A couple of years ago, it was a physical struggle to get a word out. She would bend her body over to get the word, ‘Yes’ or ‘No’ out.”

Olivia’s mom notices that there are good days and bad days where she wants to get her words out, but, “she uses three or four-word sentences when she wants to, and it’s slowly progressed where she moved a little less while working to speak. Now there are times that the physical struggle isn’t there at all.”

There are also dangers associated with SYNGAP1. “You always have to hold her hand, because she will run in any direction without warning,” Mr. Nordmoe observes. “Once she’s away from you, you can’t yell at her to stop, because she doesn’t tune in to that.”

Olivia is 6 now and loves baking and glamming up for the camera. She can also be Mom’s agent of chaos by helping in the kitchen, including taking eggs out of the fridge to crack them.

Mr. Nordmoe recalls when he gave Olivia an alarm clock at Christmas. “She was so excited! She loved it. She hugged it. She wouldn’t let me have it. She played with that alarm clock for 20 minutes!”

Olivia’s older sister, MaryAnne, who is very social, “has a difficult time with Olivia’s diagnosis,” according to her mother. “She wishes that she could talk with Olivia and interact and play how she wants to play. At birthdays the last couple of years, she’s asked questions like, ‘Olivia is turning 5. Will she be able to talk now?’”

About Olivia’s Family

The Nordmoes live about 20 minutes away from their daughter, Laura Goretski, her husband, Nathan, MaryAnne, and Olivia. Janet Nordmoe’s degree in special education helps her to be attentive to Olivia’s needs, including creating a rich home environment for their granddaughters’ visits. Dennis worked 26 years for the Detroit Health Department in substance abuse services and 20 years in community neighborhood development. He worked to better the lives of families in Detroit who were challenged by poverty, violence, drug abuse, etc.

Like most grandparents, the Nordmoes “dream of living to see our grandchild have the ability to graduate from college, get married, have a career and family, if she so chooses. These passages are out of reach unless we take effective action now. Therefore, together with other SYNGAP1 missense parents working through SynGAP Research Fund, we are launching a Missense Fund to support research to develop treatments for Olivia and others with missense mutations.”

“I want to do everything we can now rather than wish we had 10 years earlier. I want to see changes in my lifetime,” says Mr. Nordmoe.

Mrs. Goretski adds, “This experience has totally changed my understanding of intellectual disability in general. It’s not a limit – there’s a disability. Olivia is able to learn. She knows most of her upper and lower case letters, but she has an extremely hard time communicating. There is a literal barrier to her processing the world and learning, but it does not mean that there is a complete incapability.”

Advice to Other Parents

Laura Goretski came across the SynGAP Research Fund through a Google search. After joining the community, she received a call from Corey Baysden, SRF’s Community Activation Director. Mrs. Baysden offered insight and support, which led Mrs. Goretski to virtually attend the 2023 SYNGAP1 Conference, hosted by SRF. “It was great to hear from other families. You don’t want anybody going through this, and you don’t want to hear about other kids having to suffer. At the same time, it’s nice to know you’re not the only one who’s living with this. It’s helpful to know that other people are experiencing similar things, and you hear how they deal with it.”

She continues, “Take it one day at a time. Know that there is good reason to have hope, and even if it’s not a cure, some of the drug repurposing trials are fascinating. They may improve cognition and reduce seizures. Even having that alone could make an impactful difference. I think it’s hard sometimes for parents to have hope and also worry about potentially having it taken away from them. Have a little faith, and go out on that limb, and have hope.”

Mr. Nordmoe observes that “people in science are working on this in considerable detail. That’s the encouragement I get. This ‘issue’ has probably been around for hundreds of years, but this is the first time in history that we have tools to deal with it.”

“Continue to be hopeful and to interact patiently and encouragingly toward your child. Rejoice in small measures of progress,” advises Mrs. Nordmoe.

Mrs. Goretski recommends that families “look into what organizations are near them that can assist with navigating special education/IEPs/IFSPs/Early-On, transitioning out of high school to adulthood, and all things related to that world. In Michigan, we have the Michigan Alliance for Families, which provides free advocate services and parent mentors. Also, there are local and state committees/agencies, such as a PAC (parent advisory committee), LICC, SEAC, etc., and I’m sure other states have similar committees.

“Unfortunately we can’t assume that the district will automatically fulfill all of our children’s needs, so it’s important to know what is available to you and what your rights are. There were some things I didn’t know and some of the school staff didn’t know, but the advocate steered us in the right direction.”

About SYNGAP1-Related Disorder (SRD)

SYNGAP1-Related Disorder (ICD-10 F78.A1; ICD-11 LD90.Y) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SynGAP protein levels. SRF has identified over 1,400 patients to date, the number grows weekly. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SynGAP protein levels are too low, we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SynGAP patients.

Symptoms of SYNGAP1 include primarily neurological issues, including autism spectrum disorder, intellectual disability, epilepsy, hypotonia (low muscle tone), gross and fine motor delays, and visual abnormalities such as strabismus (crossed eyes) as well as gastrointestinal challenges and disordered sleep.

About the SynGAP Research Fund (SRF)

The mission of the SynGAP Research Fund (SRF) is to improve the quality of life for SYNGAP1 patients through the research and development of treatments, therapies, and support systems.

SRF was founded in the US in 2018 as a 501(c)(3) US public charity, and families created sister organizations for SRF in the UK in 2020, in Europe (Netherlands) in 2022, and in Latin America (Colombia) in 2023.

Completely family-led, SRF is the largest non-government funder of SynGAP research having committed over $6 million in grants. The founders cover operational costs, ensuring donations fund science and patient-related programs. SRF’s grant program awards grants to investigators, physician residents, and clinicians interested in studying SYNGAP1. SRF grants are intended to help researchers explore novel ideas and answer open questions related to the clinical aspects of and therapies for SRD.

For more on SRF, visit curesyngap1.org or follow @cureSYNGAP1 on LinkedIn, YouTube, Instagram, Facebook, TikTok, or X.

SRF is a member of FasterCures, COMBINEDbrain, Global Genes Foundation Alliance, Everylife Foundation Community Congress, Epilepsies Action Network, Personalized Medicine Coalition, Rare Epilepsy Network, Epilepsy Leadership Council, Alliance for Genetic Etiologies in Neurodevelopmental Disorders and Autism (AGENDA), California Action Link for Rare Diseases, American Brain Coalition, Genetic Alliance UK, Rare Disease UK, Syndromes Without a Name (SWAN UK), Jumpstart Program, Patient Worthy, Autism Brain Net, Innovation and Value Initiative, Rare Disease Diversity Coalition, Cambridge Rare Disease Network, Breaking Down Barriers, Rare-X, Mencap, IndoUSRare, and The World Orphan Drug Congress.

Read Olivia’s SYNGAP1 Warrior Story here.