SynGAP1-related intellectual disability is a rare genetic disorder caused by a variation on the SynGAP1 gene, with approximately 500 diagnosed patients accounted for globally. It leads to several neurological issues in patients, including mild-to-severe intellectual disability, epilepsy, autism, hypotonia (low muscle tone), apraxia (delayed/no speech) and impulsivity/aggression.
Because SynGAP1 disorder is caused by insufficient expression of the SynGAP protein compared to a healthy individual, one promising approach to treatment is to further activate the functional copy of the SynGAP1 gene, in order to compensate for the dysfunctional copy. A major benefit of this approach is that it is independent of the specific variation on the dysfunctional copy, and therefore can be utilized by all affected patients. However, the mechanisms regulating SynGAP expression are essentially unknown and this is a major roadblock to discovering new therapies. Epigenetic (outside, or “on top of” the genome) mechanisms hold tremendous promise because they are known to powerfully regulate gene expression.
Dr. Gavin Rumbaugh, one of the world’s leading SynGAP researchers, has highlighted the importance of studying epigenetics:
"One thing that has essentially been ignored is regulation of the gene itself. . . We do not understand how the gene is expressed, how the protein is made, and how the protein is degraded. . . Growing research through the study of epigenetic mechanisms is a great first step."
The SynGAP Research Fund (SRF) with partners from the SynGAP Global Network (SGN) intend to raise $127,000 toward funding an epigenetic study of SynGAP1 expression. This fundraising effort will directly support the work of Dr. Elizabeth Heller of the Penn Epigenetics Institute.
Dr Heller’s study will focus on investigating epigenetic mechanisms to help uncover druggable targets that can increase SynGAP expression from the “good” copy of the gene and be used to develop a treatment. The study will first uncover the cellular mechanisms that govern SynGAP1 gene activation. Next, tools will be developed to artificially activate SynGAP1 in the brain. The goal is to design an intervention that is functional at all stages of development, for all SynGAP1 children.
As an established researcher in the field of epigenetics at a leading institution, Dr. Heller is already a great choice for this work. She also has strong personal motivation: her niece is affected by SYNGAP1 syndrome. She is excited to pursue this research in earnest and considers it a privilege to enter the SYNGAP1 research field as a molecular and behavioral neuroscientist.
The SynGAP Global Network is an international collaboration of organizations furthering SynGAP related efforts and initiatives. The major contributing organizations to this project are:
· SynGAP Research Fund (SRF) -- USA
· Syngap Elternhilfe -- Germany
· Leon & Friends e.V. -- Austria
· SynGAP Research -- Australia
· Overcome Syngap1 -- Canada/France
· Syngap1 España -- Spain
· Syngap1 Sverige -- Sweden
· Our partner organizations from Ireland, Holland, Switzerland, the UK and more!
About SynGAP Research Fund (SRF): SRF is a 501(c)(3) non-profit organization and was incorporated in 2018 to improve the quality of life of SynGAP1 patients through the research and development of treatments, therapies and support systems. SRF is the largest non-government funder of Syngap research and operates under our core pillars of Collaboration, Transparency & Urgency. Our founders cover all overhead, so 100% of donations go directly to research.