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HOPE for Harvey
Home
Harvey's Story
Leadership
Donate Today!
Treatment
Events/Blog
More
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  • Leadership
  • Donate Today!
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Developing a Treatment

On 6/29/22, the HOPE for Harvey Foundation signed a contract with Everlum Bio, a rare disease lab who believes that everyone deserves a cure, no matter how big or small the disease. Everlum Bio is based in Austin, TX, and we are excited to partner with them on creating a treatment for DLG4-related Synaptopathy, focusing on ASOs and small molecule screening.  Through this relationship and in collaboration with iXcells, HOPE for Harvey successfully derived 6 induced pluripotent stem cell (iPSC) lines for DLG4 and designed some potential ASO candidates.  Due to limited binding potential at this time for Harvey's specific binding locations for ASOs, we are currently reaching out to nonprofits like n-Lorem, so we complete more research to better understand the impacts of Harvey's specific mutation and differences from other DLG4 mutations.


On 3/16/23, HOPE for Harvey signed an additional contract with Hebrew University of Jerusalem and Rami Aqeilan's lab in collaboration with the SHINE Foundation to support the research and development of a virus-based gene replacement therapy called an AAV.  Dr. Aqeilan's lab has successfully identified an AAV and has developed neuronal lines and brain organiods (3D neurons) of various DLG4 mutations.  Dr. Aqeilan's lab has shown that introducing a good copy of DLG4 does appear to improve symptoms in mutated lines, including Harvey's.  They are now working on grant and commercial funding to continue testing their AAV for DLG4. 


In the summer of 2023, the HOPE for Harvey Foundation applied for two DLG4 animal model grants at Jackson Laboratories (Jax) and the Center for Precision Animal Modeling (C-PAM) at the University of Alabama at Birmingham (UAB), and both were accepted and are currently in progress. After a failed attempt in December 2023, Jax re-engineered their mouse model carrying Harvey's specific missense mutation, and had their first pups born in May 2024.  Jax was able to identify male mice carrying the transgene and was able to successfully breed those mice in July 2025.  Jax is continuing to breed these mice and identify treatable symptoms.  We hope to be ready to send these mice out to labs to test various gene therapy approaches in the coming months.


In the spring of 2024, HOPE for Harvey began working with NeuCyte on generating iNeurons from the iPSC cell lines in order to test treatments and better understand how different variants function, including Harvey's mutation.  Using multi-electrode arrays (MEAs), NeuCyte observed differences between the mutated and healthy neurons.  In addition, NeuCyte has run RNAsequencing on Harvey's mutant neurons compared to healthy neurons and has identified differences in related proteins and impacted pathways, which could be treated with readily available drugs.  Harvey's family has begun exploring those drug candidates.  We hope to use AI technology to narrow our target list from all of the potential targets identified.  One we have all of the neuronal lines, NeuCyte has run several tests, including more MEA data and various assays such as SiRNA designs to look at what 'knocking down' the mutant copy would do to the mutant neurons compared to the healthy neurons, which does support that a potential ASO strategy could be beneficial for Harvey.  HOPE for Harvey is continuing to explore this pathway by connecting with the n-Lorem Foundation.


In August 2025, HOPE for Harvey signed a contract with Grann Pharmaceuticals to develop a lipid nano particle (LNP), which will carry a healthy copy of DLG4 mRNA into the body through regular infusions in order to code more healthy DLG4 protein.  Grann has successfully entered a recent clinical trial for Retts Syndrome using this strategy in record time.  Due to the speed, safety profile, and efficacy so far, HOPE for Harvey has decided to primarily focus on this treatment pathway for the time being.  Grann Pharmaceuticals has developed a one-stop shop and is currently supporting this rare disease research at cost, which allows small organizations like HOPE for Harvey the opportunity to create a therapeutic for rare diseases.  Grann will assist HOPE for Harvey in the pre-clinical development and testing of the LNP mRNA in mice carrying Harvey's mutation while looking for improvements in mice symptoms, they will conduct safety/toxicology studies in those treated mice, they will assist HOPE for Harvey through the FDA application and approval for the LNP mRNA treatment, Grann will conduct the manufacturing of the LNP, and they will assist in coordinating/organizing the clinical trial and treatment protocol for HOPE for Harvey in collaboration with COMBINEDBrain.  It is possible HOPE for Harvey will be entering clinical trials for this LNP mRNA in early 2027.


Treatment Pathway

As of August 2025, we are currently working on these specific pre-clinical development tasks with funds from our GoFundMe/GiveButter Campaigns and HOPE for Harvey Foundation Fundraising Efforts with the following estimated costs:  

  • Induced Pluripotent Stem Cells (iPSC) derived neurons ( 3 lines including Harvey's dominant/negative mutation, 1 haploinsufficient line, and 1 control-$49,750 total)-all lines completed
  • Commercial iPSC Line for Quality Control (3 lines at $33,750)-completed
  • Neuronal Differentiation for 3 neuronal lines (haplo, WT, and Dominant/Negative line) (~$95,000), Dom/Neg LoF and WT line completed
  • MEA data: $31,000, first two rounds completed
  • RNAseqeuncing: $6,000, completed, analysis underway
  • DNA Long Read Sequencing for treatment attack spots/SNPs ($11,500)-completed
  • SiRNA designs (being donated by researcher), completed and ready for use, costs to order ~$1,500
  • SiRNA knockdown experiments: Completed
  • Animal Models: FREE - currently have two grant applications accepted at Jax and UAB respectively for a Harvey dominant/negative mouse/LoF and a nonsense, haploinsufficient rat model-both in progress-no cost (grants)
  • C Elegan worm Model: FREE UT Austin has Harvey specific mutation for possible small molecule screens (grant-no cost)
  • ASO exploration ($8,000)-completed, not feasible to proceed at this time given without above research data, continuing to explore with n-Lorem grant application based on NeuCyte SiRNA findings
  • Project Management/Research Consultation on Projects, ~$15,000/yr
  • AAV development/development of neurons and organoids at Hebrew University-HOPE for Harvey's responsibility ($20,000)-completed as well as MEA testing and delivery of AAV in organoids showing that Harvey's mutation positively (symptoms improved) responded to adding a good copy of DLG4
  • Base editor (design donated by MIT researcher team); Cost of work will be completed at later date once mouse is fully bred and phenotyped
  • LNP mRNA pre-clinical mouse testing, Safety/Toxicology Studies, FDA Application and Approval Process, Assistance with Patent Application, Guidance and Assistance on Clinical Trial Protocol, Clinical Trial Dose Manufacturing ~$500,000
  • Initial Clinical Trial Cost to Family for N of 1 mRNA LNP ~$40,000
  • Expanded Access Clinical Trial TBD-Will seek commercial partner
  • Shipment costs of pluripotent stem cell and neuronal lines to various labs ($1,000-$3,000 per shipment), ongoing


Current Total Costs: ~$828,500 without the clinical trial costs to family


Currently need to raise ~$230,000 to finish these projects.  If we can fundraise another $100,000 to help offset these costs, this is achieveable with additional familial donations, and a treatment for DLG4 is a real possibility.


HOPE for Harvey is currently exploring various grant opportunities as well to help offset these and future research expenses

AAV Researcher, Rami Aqeilan

Check-out this video from our AAV project with Rami Aqeilan, Hebrew University of Jerusalem

Research

Currently there are no treatment options for DLG4-related Synaptopathy.  We hope to change that with your help! 100% of donations will support the development of various treatment modalities. 


Due to advocacy by HOPE for Harvey Foundation, four additional academic labs recently started research projects on DLG4-related Synaptopathy:

  1. The Yu Lab https://theyulab.org
  2. Matt Might, as part of the Hugh Kaul Precision Medicine Institute https://www.uab.edu/medicine/pmi/matt-might
  3. Jackson Laboratories https://www.jax.org/
  4. Hebrew University of Jerusalem-Rami Aqeilan's Lab https://lautenbergcenter.org/people/faculty/prof-rami-aqeilan/
  5. INGENUITI Study at UC Berkeley https://innovativegenomics.org/ingenuiti/
  6. Neuronal Work at NeuCyte Translatable Neuroscience https://www.neucyte.com/
  7. Brumback's Lab at UT Austin https://www.brumbacklab.org/
  8. Broad Institute https://www.broadinstitute.org/

Francis Collins Urges Gene Therapy Community to Scale Efforts to Tackle Rare Diseases

"Collins concluded by thanking his audience while urging them to do more. 'Of nearly 7,000 genetic disorders, only 500–600 have an FDA-approved therapy,' he said. The goal is to develop therapies for the thousands of disorders for which patients and their families are still waiting in vain."

Read article in Genetic Engineering & Biotechnology News

Rare recessive mutations pry open new windows on autism

"After excluding genetic variants that were also found in the control group and in a separate large cohort of more than 60,000 individuals without autism, Doan, Yu and colleagues were left with 41 genes that were knocked out only in individuals with autism. Overall, the researchers estimate that these genes explain another 3 to 5 percent of all cases of autism (2 percent from loss-of-function mutations, and 1 to 3 percent from missense mutations)."

Read article in EurekaAlert!

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