Events/Research Updates

 During Rare Disease Week this year, I am reflecting on how exhausting and busy the last 5 years have been since Harvey was born. From waking up at 5am to work with Harvey as a baby on learning how to roll over to beginning the long journey of getting his diagnosis to the countless hours of therapy, doctor’s appointments, and crying myself to sleep. You can’t fathom what a special needs family goes through until you live the life yourself, even with almost 20 years of experience of working with individuals with disabilities. I’ve watched my son have seizures and felt helpless, have electrodes strapped to his head and needles poked in his arms while he screams, and restrain him everyday to do simple things like brush his teeth and give him medicine so he will sleep at night. But, we’re also fortunate. Fortunate to live in a country with amazing doctors, world-leading researchers, amazing therapists and teachers, wonderful nurses, and access to publicly-funded resources like early-childhood and Medicaid who have helped Harvey learn how to sit-up, take his first steps, and work on ways to communicate. And, I still have HOPE! HOPE these services will continue for my son and children like him. I have HOPE that life-changing research will allow his neurons to connect properly and allow him to learn. I have HOPE for a cure for the generations to come, because there will be future generations of individuals born with genetic mutations. Many of these mutations are now being linked to other life-impacting disorders like ADHD, Cerebral Palsy, Learning Disabilities, Autism, and Cancers.

In the almost 3 years since we started HOPE for Harvey, we have made huge strides in research on DLG4. We are fortunate to get to work with some of the world’s best geneticists, neurologists, and neuroscientists. In labs at Harvard, they have created a DNA gene editor, and in December 2024 that gene editor, showed 75% accuracy in correcting Harvey’s mutation in mouse cells. In addition, almost 50 new mice were born at Jackson Labs in Maine in January 2025, so we can hopefully use these mice in further validation studies. In addition, we have taken Harvey’s blood and had stem cells made, and now those stem cells have been derived into neurons at our neuronal lab, NeuCyte. These neurons carry Harvey’s mutation, have healthy controls, and we are working on a line which mimics many other DLG4 mutations. We are now narrowing down experiments with all of the data we have collected about how Harvey’s mutation is different from healthy neurons so we can measure whether readily available drugs could improve symptoms. We also hope to use these neurons to verify whether a RNA-based treatment could help improve Harvey’s symptoms. In addition one of Harvey's neurologists and her team at UT Austin and outside collaborators have made a worm model of Harvey's mutation, and they plan to screen readily available drugs to help improve the worm's symptoms.  We also helped kick-start a gene therapy study for the greater DLG4 population, and those researchers have applied for additional grant funding to continue their work. We have created so many pathways toward a treatment, and we couldn’t have done this work without all of our donors, so thank you. Thank you for your continued support and thank you for your generosity.

 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