Updates from the Director of Scientific & Clinical Initiatives
August 2024
As the Dup15q Alliance continues our search for a new Director of Scientific and Clinical Initiatives, members of our Board and Scientific Committee will continue to provide updates in our monthly newsletter. We are in an exciting place in advancing research, and ultimately, therapeutic development. We hope you’ll continue to follow along!
LEARN
Publication Alert
When a loved one from our community passes away, many families make the deeply generous and selfless decision to donate brain tissue to Autism BrainNet. Brain donation is an invaluable gift, offering researchers the rare chance to study Dup15q syndrome directly in the human brain. This enables scientists to verify that findings from animal and cell studies are relevant to human patients. Additionally, validating therapeutic targets in human brain tissue increases the probability of these target successfully translating into new therapies that are tailored to the unique needs of our community.
While the decision to donate is deeply personal, its impact on advancing research is profound. In July, a research team from Harvard published an important paper on the expression of duplicated genes in Dup15q syndrome. In a follow-up interview, the lead researchers emphasized that their findings would have been impossible without access to donated brain tissue. Our hearts break when we think of loved ones lost in our community, but we are immensely grateful for the families who choose to make this donation in their time of loss.
We’ll be sharing more about the significance of this research in an upcoming blog post, where we’ll also summarize the study’s key findings. If you’d like to read ahead, you can find a link to the paper here: Harvard Study Link.
For more information on Autism BrainNet and the gift of brain tissue donation, please visit Autism BrainNet.
TREAT
Genetics Recap
As part of the Dup15q Alliance’s efforts to accelerate therapeutic development, we are pleased to partner with the U.Penn Orphan Disease Center to offer a grant of $47,038. We are soliciting applications that support work towards a precision therapeutic for Dup15q syndrome.
Therapeutic targets of interest include the gene cluster encoding GABAA receptor subunits and maternally imprinted UBE3A.Treatment for Dup15q is mainly limited to interventional therapies and the use of medication for symptomatic management of medical complications.
While we are keeping the grant funding opportunity broad in scope, preference will be given to awards that focus on three areas:
1. Model systems that explore any aspect of the syndrome’s pathophysiology, including, but not limited to, identification or confirmation of the role of the duplicated genes and genotype/phenotype correlation.
2. Identification of biomarkers for Dup15q, including but not limited to molecular, neuroanatomical, neurophysiological, or physiologic.
3. Development of approaches or systems that may lead to targeted therapeutics: ASOs, siRNAs, small molecules, gene editing technologies, etc.
CURE
Genetics Recap
Understanding the genetics behind Dup15q syndrome is key to developing effective therapies. Dup15q is caused by an extra piece of genetic material from chromosome 15 at the 11.2-13.1 region. This results in extra copies of several genes, leading to the symptoms we see. Single-gene disorders are often easier to address with gene therapy, but the involvement of multiple genes in Dup15q makes finding treatments more complex.
A key clue lies in the difference between maternal and paternal interstitial duplications. Those with maternal duplications show the typical symptoms of Dup15q, while those with paternal duplications have a very mild clinical presentation or no exhibit symptoms at all.
Why is there a difference? The likely answer is UBE3A, a gene normally only expressed from maternal chromosomes. Therefore, maternal Dup15q leads to an extra copy of active UBE3A, while paternal Dup15q leads to an extra copy of silenced UBE3A. This suggests UBE3A may be a crucial target for therapy. By reducing its excess activity in maternal duplications, researchers hope to address some of the underlying causes of Dup15q syndrome.
While there is still much to learn, these genetic insights bring us closer to developing targeted treatments for Dup15q.
