Harvey's Story

In March of 2020, we gave birth to our second child, Harvey, in Seattle, Washington, just three days prior to the first COVID-19 lockdown. We felt so fortunate to head home with what appeared to be a healthy little boy. But by six months, we began to notice that Harvey was struggling to meet developmental milestones like head control, screaming during tummy time, lack of use of his right arm, ongoing concerns with eye crossing or strabismus, and he wasn’t showing any signs of learning to crawl.

By eight months, we were gravely concerned and sought guidance from our pediatrician who immediately sent us to Seattle Children's Neurology, who expedited Harvey’s case based on presenting concerns. It was December 23rd, 2020, as many families were looking forward to holiday festivities after such a stressful past year, we were about to embark on the hardest journey of our lives.  

In early January 2021, just a few days prior to our move back to Austin, Texas, Harvey underwent a brain MRI and several blood panels, as Harvey’s Neurologist was concerned that Harvey was presenting with signs of a perinatal stroke. When the results game back with no concerns on his bloodwork and a fairly normal brain MRI (just delayed myelination), we felt so relieved. Maybe things weren’t going to be as devastating as we had expected. Little did we know it would be an almost year-long odyssey from first concerns to receiving a diagnosis.  

As soon as we relocated back to Austin, we began seeing Neurologists at Dell Children’s, who after reviewing the brain MRI and bloodwork results, decided to order our first round of genetic testing. While we waited for results, we also were instructed to see a whole slew of specialists including Orthopedists, Ophthalmologists, Audiologists, Gastroenterologists, Geneticists, EEGS, and so on, —with one specialist literally remarking, ‘he’s a mystery'—as well as a plethora of therapy: Occupational Therapy, Physical Therapy, Speech and Feeding Therapy, Vision and Mobility Therapy, and Applied Behavioral Analysis therapy due to significant and ongoing delays in: motor skills and muscle tone including repetitive behaviors such as rocking and odd hand mannerisms; speech; feeding; and socialization concerns, including inappropriate eye contact, which eventually led us to a Autism Spectrum Disorder diagnosis as well, which is often co-mormid with genetic disorders like DLG4.

Finally, when Harvey was nearly 18-months-old, after two rounds of genetic testing, which ultimately included Whole Exome Sequencing (WES), we received Harvey's diagnosis of an ultra-rare genetic disorder, DLG4-related Synaptopathy due to a de novo ("random") missense (single letter) mutation (C became a T) on the 19th exon of one of Harvey's two DLG4 alleles.  DLG4 'codes' the production and structure of the PSD-95 protein. PSD-95 is vital protein that scaffolds with several other proteins to build neuronal connections in the brain and is vital for learning and memory.

We do not know what Harvey’s future holds, but given his type of mutation, he appears to a high likelihood of continuing to have a severe cognitive disability, inability to speak, seizures, ongoing repetitive behaviors typical of children with an Autism Spectrum Disorder, and lack of motor control. This means Harvey may never walk independently, speak, or feed himself without treatment.

Immediately following Harvey’s diagnosis, we found a parent support group of about 30 other families around the world affected by DLG4 and began exploring any treatment options. That number has since grown to close to 200 individuals worldwide similar to Harvey, with Harvey sharing his mutation with only one other individual in the world.  We have learned so much about genetic treatments available today, such as the amazing results of Spinal Muscular Atrophy (SMA) treatments, including ASOs and CRISPR for rare eye diseases and are working with world-renowned researchers and consultants. Please visit our research page and ClinicalTrials.gov to learn more about these amazing treatments. We are now embarking on a journey of developing a treatment for DLG4 and are asking for your help!      

With the guidance of several world-renowned researchers and experts including, but not limited to: the Yu Lab at Boston Children's, NeuCyte Translatable Neuroscience, iXCells Biotechnologies, Dr. Rami Aqeilan's lab at Hebrew University at Jerusalem, Jackson Labs in Maine, University of Alabama at Birmingham's Precision Medicine Lab (UAB), the INGENUITI Study at UC Berkeley, the Broad Institute at MIT and Harvard, the University of Texas at Austin, COMBINEDBrain, Grann Pharmaceuticals, and with the guidance of researchers studying DLG4 in Denmark and Canada, we are exploring treatments, which include:

As of August 2025, the HOPE for Harvey Foundation has multiple research projects in the works, with 6 projects targeting specific treatment pathways for DLG4.  These projects include:

1) Targeting mRNA: Through the use of lipid nano particle (LNP), Grann Pharmaceuticals has shown through the start of a recent clinical trial for Retts Syndrome, that these particles can pass the blood brain barrier and carry good copies of mRNA throughout the body through regular infusions.  These mRNA infusions can help compensate for DLG4 mutations, and allow for healthy expression of DLG4 proteins to help build better brain plasticity; and therefore, create developmental gains.  This project is in the works currently.  Grann will also be our partner on testing the mRNA on mice carrying Harvey's mutation, on our safety/toxicology studies, FDA approval, manufacturing, and coordination of our clinical trial.  We could be potentially be in clinical trials in early 2027!  Due to Grann's speed, the safety profile of this mRNA treatment, and the incredibly low, at-cost price Grann is offering small rare diseases, this will become our primary focus for our research moving forward.

2) Creating Models to Test Treatments: Through advocacy, grant applications, and funding, the HOPE for Harvey Foundation has helped create 5 different types of models that can be used to test treatments.  1) Mouse model at Jackson Labs in Maine, which carries Harvey's DLG4 mutation - Mouse Model is complete and the colony is currently being expanded and monitored for symptoms; 2) Neuronal Lines, which carry Harvey's mutation as well as control lines, which can be used to test various treatment options and a variety of drugs as well as identifying impacted pathways through RNAsequencing - Work is completed including RNA sequencing, waiting on full analysis; 

3) C. Elegan/worm model, which carries Harvey's mutation and can be used to test large drug libraries to try and improve symptoms - Model is complete and lab is currently working on larger drug study at UT Austin; 4) Stem cells lines (iPSC lines), which can be used for drug testing - Completed and transformed into neuronal lines and sent to other labs for further analysis; 5) Rat Model at University of Alabama at Birmingham-currently in the works/awaiting additional NIH funding

3) Targeting DNA: Through a non-harmful virus called an AAV, a healthy copy of DLG4 is sent into the body.  This research is being conducted at Hebrew University and initial preclinical analysis of Harvey's neuronal lines shows this is an effective strategy for Harvey and other DLG4 mutations.  Please see the video of the researcher explaining how it works on our website under treatment!  

4) Targeting DNA: We are also working on a gene editing strategy (which involves using a molecule to bind to Harvey's DNA to change Harvey's mutated 'T' back to a 'C') with researchers at Harvard.  We hope this work will continue in the coming months, as the mouse phenotyping moves along.

5) Targeting RNA: Through a synthetic molecule called an ASO.  We have had some initial exploration of an ASO strategy on our neuronal models at NeuCyte, and we are currently in conversations with a nonprofit called n-Lorem to help us continue this work.  

6) Targeting Protein: Through testing readily available drugs and peptides on Harvey’s mutated neurons for positive effects on his neuronal functioning, impacted pathways, and protein expression.  This work is currently being explored at a private company called NeuCyte.

In addition to these efforts, we have also helped initiate a phenotype study of DLG4 at the Children's Hospital of Philadelphia in collaboration with Dr. Tümer's lab in Denmark, and patient registries/natural history data collection.

We have raised over $500,000, and in 2025-2026 we are hoping to raise another $100,000, in order to cover the cost of our LNP mRNA project, the primary focus of our ongoing work at HOPE for Harvey.  If we keep on this track, we aim to be entering clinical trials in early 2027.