Gene Editor and Neuron Update End of Year 2024
A treatment is Possible
When we started HOPE for Harvey 2.5 years ago, we had hoped to create a model to test various drugs on DLG4 mutations, but we were blown away by how many more doors have opened in the past 2.5 years. This week culminates a big milestone for us. This week our mouse lab will send mouse tissue from a mouse carrying Harvey's mutation to the B
When we started HOPE for Harvey 2.5 years ago, we had hoped to create a model to test various drugs on DLG4 mutations, but we were blown away by how many more doors have opened in the past 2.5 years. This week culminates a big milestone for us. This week our mouse lab will send mouse tissue from a mouse carrying Harvey's mutation to the Broad Institute at Harvard to test a gene editor. The gene editor will knick the DNA in the mouse tissue and bind a small molecule that has been designed to 're-code' Harvey's mutated 'T' back to 'C.' The lab will measure how well the 're-coded' DNA can generate healthier neurons that fire and bind appropriately. These gene editors will hopefully help kids like Harvey to build healthy neuronal connections in their brains, so they can start learning more and hopefully avoid debilitating seizures.
In addition, our amazing neuronal lab, NeuCyte and COMBINEDBrain Consultant, Anna Pfalzer, who have truly gone above and beyond, created this video https://lnkd.in/g69q6QHb to summarize the work we have been doing together this past year. They have helped us better understand the impacted pathways and firing issues caused by Harvey's mutation and other DLG4 mutations, so we can target readily available drugs to mitigate these impacts.
Let's make these treatments a reality for kids like Harvey, because I can't imagine a life where I haven't tried everything I possibly can to help my son and kids like him. Because this life is more than hard … it’s exhausting … it’s relentless … it’s gut-wrenching, and it will never change, if we don’t do something ourselves.
Many thanks, the HOPE for Harvey Foundation and our sweet guy, Harvey
October 2024 Society for Neuroscience Collaboration Presentation with HOPE for Harvey, NeuCyte, and COMBINEDBrain
Check out these recent highlights from some of the neuronal work HOPE for Harvey has been sponsoring with NeuCyte in collaboration with COMBINEDBrain. Excited to share more data as the research progresses toward a treatment pathway for DLG4!
2nd Annual HOPE for Harvey Impact Report
Hello HOPE for Harvey Supporters
Last month we marked 2 years as a nonprofit organization, and we took some time to reflect on what we have accomplished because of supporters like you, and would like to share our amazing progress with you all and hope to be as transparent as possible in where your dollars are going. Excited for the year to come and the opportunity to start testing treatments for DLG4 on the animal and cell models HOPE for Harvey has helped create! Once we have updates, we will be sure to share them with you.
Spring 2024 Updates
Research Updates
As we approach two years as a nonprofit organization, I wanted to share with our donors and community the progress HOPE for Harvey has made over the past two years.
We have several research teams we have been coordinating with since our inception. Some paths have given us curveballs, but we will continue to work toward a treatment, because we have nothing but time for our sweet boy and so the many others impacted by this devastating disease for decades.
Despite the many setbacks we have experienced to create animal and cell models, which would be used to test various treatment modalities, we have had some recent success in the past couple of weeks. Jackson Labs in Maine is now working on several new constructs for a Harvey mouse, and hopefully, one of these mouse designs will be able to survive Harvey’s debilitating mutation. We also heard in the past two weeks, TWO LABS HAVE NEURONS!!! This is a huge milestone, and these neurons can now be used to potentially test readily available drugs to see if we can improve cellular functioning as well as test one of our novel gene or RNA therapies!
In addition, we have also spoken to some new therapeutic research developers recently to add to our team. One lab in San Diego also develops RNA-based ASOs, and they have Harvey’s genetic information. They are using their proprietary technology to take another pass at any potential ASO designs, which could help stop Harvey’s mutated copy from coding a mutated protein. For unique mutations, this company will often do this work philanthropically, and then pass along their ASO designs to partners like St. Jude or the nonprofit n-Lorem, which would be amazing for our small organization.
Our wonderful, 'newish' consultant from Vanderbilt is also looking into creating some plasmid lines to potentially measure what Harvey’s mutation is actually doing at the cellular level, which is a much harder than one would expect … but could help us better determine if existing drugs could positively impact Harvey’s mutated or healthy protein expression.
In addition, we just heard from our Israeli team partners about some wonderful, but unfortunately confidential for now, progress in their lab toward an AAV gene therapy for DLG4, which sends in a good copy of the gene to make up for the mutated copy’s dysfunction.
Our consultant also introduced HOPE for Harvey to a new, and amazing researcher in Canada who is exploring gene therapies for other genetic disorders. She ever so kindly offered to do some exploratory work in her mouse lab on DLG4 as well! She is also interested in pitching some multidisciplinary grants to the NIH on our behalf in the coming months. In addition, her research is focused on using the Covid vaccine capsids/coatings to package gene therapies, as a cheaper and potentially safer (less toxic) way to deliver these life-changing therapies. We’re super excited to see where this pathway could take us!
Although we are having to delay trialing some base editing designs from a team at the Broad Institute, until we have a viable mouse model, we remain hopeful that this could be a life-changing strategy for Harvey longterm, as it would directly target his single-letter mutation through an enzyme delivered intrathecally. This is new wave technology, and is going to change lives!
Also, all six of our current iPSC lines are at the Broad Institute now, and they’re working on some potential designs for screening existing small molecules/drugs available today.
Harvey is also now enrolled in Jennifer Doudna’s INGENUITI study at UC Berkeley. We have shipped them blood samples, and they are currently making their own iPSCs /stem cells and doing whole genome sequencing. Jennifer Doudna was a co-recipient of the Nobel Prize in Chemistry in 2020 for her development of CRISPR, which allows researchers to cut and alter genes.
In addition, one of Harvey’s amazing Neurologists, who also conducts research, made a Harvey worm, and they are currently studying the worm and Harvey’s mutation, to determine if there is a path forward to study how the worm’s motor, social, GI, and neurological development could change/improve when introducing small molecules/drugs currently available.
Lots of projects, lots of steady progress, which we could not do without our generous and amazing donors, so THANK YOU ALL!
-The HOPE for Harvey Foundation
February 2024 Update
We'll Continue to Persevere
This has truly been one of the hardest weeks since we began our journey toward a diagnosis for Harvey over 3-years ago. In addition to Harvey starting seizures this week, we found out that the mouse model we have been working on for over a year is not viable after the quality testing that was completed. To have one of the world’s premier mouse labs struggle to create an animal model, well, it’s honestly heart-breaking. We are so fortunate, though, that Jackson Labs is going to re-engineer the mouse model and try again, but this is a significant setback and blow to our family and foundation, as we now begin the horrible journey of seizures. Seizures for DLG4 strip away the lives of our children. We have to watch them whither away and lose one skill after another, and some end up wheel chair bound with feeding tubes and no ability to communicate, and this pain doesn’t just last for a few years, it can last for decades, with individuals living into their 50s and 60s sometimes across rare genetic disorders. So, I’m not ready to give up HOPE for my son, HOPE for DLG4, or HOPE for rare genetic disorders, and we will take this setback in strides and HOPE that it gives the genetic field more time to learn and understand the safety and efficacy of gene therapies and novel approaches like base editing. We will continue to have HOPE that Harvey and other individuals with DLG4 will one day be the fortunate recipient of a life-changing treatment. Some exciting news is our new neuron lab received our stem cells this week, and we will begin our third attempt at differentiating DLG4 neurons. In addition, we sent blood to begin the INGENUITI study at UC Berkley as well, which is Jennifer Doudna's study, who was one of the 2020 Nobel Prize winners in Chemistry for her development of CRISPR, the technology that allows scientists to 'cut' DNA so it can be 'reprogrammed,' and our AAV gene therapy work in Israel continues. I am beyond grateful for the outpouring of calls, messages, flowers this week, as we try and deal with the grief of a new stage of life for Harvey, so thank you! Thank you for your support, and we hope and pray that in 2024, we will find a path forward. #hopeforharvey #curedlg4