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FAST Funded
Research

Current Trials
& Studies in AS

2020 Science
Summit

Roadmap
to a Cure

Research Grant
Application

FAST’s Roadmap is focused on three elements supporting therapeutic approaches that have the potential to reverse the effects of the disorder in children, teens and adults. 

Gene Replacement Therapy or Paternal Gene Activation

FAST is funding research in gene or protein replacement therapy and paternal gene activation therapy.

Gene or protein replacement therapy delivers healthy copies of the UBE3A gene or protein to compensate for the missing or underperforming gene. Treatment is delivered via a viral capsid called Adeno-Associated Virus (AAV-GT) or through Hematopoietic Stem Cell therapy using a Lentivirus (HSC-GT).

Paternal gene activation therapy, in AS referred to as “stopping the stop”, works to activate the normally silent paternal gene to compensate for the underperforming or missing maternally inherited gene. These therapeutic platforms include antisense oligonucleotides (ASOs), CRISPR-CAS9, CRISPR-CAS13, shRNA, and others. Currently ASOs are being evaluated in human clinical trials for AS.

Downstream or Symptomatic Therapy

Downstream therapy includes drugs that treat the symptoms of Angelman syndrome like seizures, sleep, behaviors, etc. There are many drugs that are already approved by the FDA that might be useful for treating AS, but are not labelled for AS. Finding these drugs and showing that they can be repurposed can help to bring new treatments for AS.

Therapeutics being targeted often improve synaptic function and communication between neurons in the brain thus improving symptoms and therefore quality of life. Different strategies being pursued include: novel compounds or peptides, ketone supplements, anti-inflammatory or regenerative medicines, and GABA replacement therapies.

Prepare!

As FAST helps to prepare for clinical trials there are many important things that must  be supported. Firstly, creating animal models and cell lines for each genotype, or type, of AS is important to ensure that we know how drugs can behave in different individuals. FAST has created a rat, pig and numerous mouse models of AS. Additionally, FAST supports the Global AS Registry and the AS Natural History studies that collect key data from those living with AS to understand the impact AS has on things like communication, sleep, gross/fine motor skills, and seizures. This data is used to inform research and trials so that we can ensure meaningful change can be measured with effective therapeutics.

The Angelman Biomarker Outcome Measures (ABOM) consortium was established to be a pre-competitive space to collaborate across AS patient centered organizations, pharmaceutical companies, and both basic and clinical researchers, to determine what symptoms and endpoints, as well as more objective biomarkers, would be best measured to show the most impact after a successful therapeutic. This consortium has been incredibly successful in bringing all stakeholders to the table to collaborate in the most productive way.

FAST has funded over $20,000,000 towards translational research for Angelman syndrome.  For more information on specific grants FAST has funded, go here.

Antisense oligonucleotides (ASOs) used in the treatment of Angelman syndrome focus on preventing the paternal UBE3A gene from being silenced – a condition caused by the UBE3A antisense transcript (UBE3A-AS). By “knocking down” the UBE3A-AS, the paternal gene becomes active, expressing functional UBE3A. ASOs are delivered intermittently through a lumbar puncture into the CSF and, while not a one-time treatment, can be repeatedly administered to a patient over a long-term.
David Segal, Ph.D., Jill Silverman, Ph.D., and the team at the University of California, Davis received a grant from FAST to build a lab devoted to Angelman syndrome (AS) research, establishing a stable infrastructure in which this team can evaluate multiple therapeutics simultaneously through, at least 2025. The Infrastructure Grant will create a new generation of scientists focused on AS research with combined expertise in molecular and behavioral components of AS; provide lab equipment and supplies; maintain AS cell lines and rodent model colonies at the University and provide long-term stability for this dedicated team to keep their focus on identifying and evaluating potential therapeutics for the treatment of Angelman syndrome.
Multiple pharmaceutical companies have potentially promising therapeutics for the treatment of AS. However, they do not have expertise in AS, or the specific tools necessary to properly evaluate these drugs for this population. This Infrastructure Grant allows AS experts to provide those services and elucidate if a potential therapeutic warrants further development toward potential human clinical trials.

The Impact

A cure for Angelman syndrome will have a tremendous impact on society at large. The gene that causes Angelman syndrome has been linked to several other diseases and genetic disorders involving learning and memory. The work FAST researchers are doing may be the gateway to therapies for other disorders that affect the lives of millions, especially those with other neurodevelopmental disorders.
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