Beginning in early 2012, FAST began funding the Dindot laboratory at Texas A&M University to understand the mechanism by which UBE3A-AS turns off the paternal UBE3A allele, why the paternal UBE3A allele is off in neurons, and how that process may be circumvented as a potential therapy for AS.

Research in the Dindot laboratory identified an investigational antisense oligonucleotide (ASO) that, through extensive preliminary studies, has been shown to interfere with imprinting of the paternal UBE3A allele. In late 2017, FAST formed GeneTx Biotherapeutics LLC (GeneTx), a for-profit limited liability company to develop this ASO for potential future use in a Phase I clinical trial.

Angelman syndrome (AS) is a rare neurogenetic disorder caused by the loss of expression or function of the maternally inherited ubiquitin-protein ligase E3A (UBE3A) gene in the brain. The maternal-specific inheritance of AS is due to genomic imprinting of UBE3A, a rare, naturally occurring phenomenon in which one allele is turned on and the other allele is turned off. An allele is a copy of a gene inherited from one parent. The UBE3A gene is subject to neuron-specific imprinting, creating a situation in which the maternal allele is on and the paternal allele is off. The paternal UBE3A allele is turned off in neurons by the UBE3A antisense transcript (UBE3A-AS).

Genomic imprinting of UBE3A creates a unique opportunity to develop targeted therapies for AS, as the paternal UBE3A allele is capable of producing the UBE3A protein. If turned on in neurons, the paternal allele could be a source of UBE3A protein in the central nervous system of AS patients, replacing the UBE3A protein that is normally made from the maternal allele.

FAST distributed a news release about GeneTx on Feb. 22, 2018.

GeneTx Q&A

Q. Why did FAST start a separate, for-profit company to develop a potential treatment for AS?

A. There are several reasons why FAST started a separate, for-profit company to develop this promising therapy for AS. First and foremost, FAST wanted to ensure that the development of this treatment moves forward in the most expeditious and detailed manner possible, with the primary goal of moving this treatment into a Phase 1 clinical program if preclinical studies support further investigation. In the long term, these efforts may also allow GeneTx to have valuable input in decisions regarding pricing, access and patient assistance programs. Lastly, if successful, revenue generated from GeneTx will be used to expand the scope of research and outreach funded by FAST, with the ultimate goal of developing meaningful and effective therapeutic options for AS.

Q. Who is the current leadership of GeneTx Biotherapeutics?

A. Paula Evans, chairperson of FAST, serves as chief executive officer of GeneTx Biotherapeutics. Allyson Berent, chief science officer of FAST, serves as chief operating officer of GeneTx Biotherapeutics. Dr. Scott Dindot, pending approval from Texas A&M University, will serve as chief science officer of GeneTx Biotherapeutics. Dr. James Wilson of University of Pennsylvania and Dr. Arthur Beaudet of Baylor College of Medicine each serve as voluntary scientific advisors to GeneTx Biotherapeutics. There are other voluntary advisors who are assisting the leadership of GeneTx.

Q. Are there any conflict of interest (COI) issues with FAST board members serving both organizations?

A. Yes. FAST sought extensive, outside legal counseling on COI issues and has implemented several safeguards to protect both FAST and GeneTx. In June 2018, Paula Evans and Allyson Berent were granted equity in GeneTx Biotherapeutics, LLC and at the direction of GeneTx’s investors, were moved from voluntary positions to compensated positions.

Q. What are the next steps for GeneTx Biotherapeutics?

A. GeneTx is currently conducting Investigational New Drug (IND) enabling studies on the investigational ASO, which is now referred to as GTX-101.

Q. When will GTX-101 be in clinical trial?

A. This will depend on the outcomes of the IND studies as well as important discussions with FDA regulators. Based on the outcome of these IND enabling studies and discussions with regulators, we hope to be ready for Phase I studies in late 2019.

Q. Who owns GeneTx?

A. Currently, FAST is the majority owner of GeneTx, and Texas A&M University System has minority ownership provisions. If GeneTx takes on investors, or hires additional professionals, then the ownership of GeneTx will change. At this time, GeneTx is not seeking any investors.

To ensure FAST is able to continue funding groundbreaking research to cure Angelman syndrome, kindly consider making a donation and creating a Cure Angelman Now (CAN) personal fundraising page.