Hi Cure,

Our preparations for International Angelman Day are fully underway, including video content, social media templates that you can use, and ways to take action!

You can get started by sharing your Moment of Hope below — and stay tuned for many more ways to participate in IAD.

If you have updates you would like to be included in next week’s newsletter, please email us at info@cureangelman.org.

This week, we continue with the focus on FAST’s 4 Pillars in the Roadmap to a Cure 2.0, highlighting Pillar 3 – Downstream Targets.

Pillars 1 and 2 focus on UBE3A, either fixing mom’s gene or reactivating dad’s copy, while Pillar 3 concentrates more broadly on affected processes that may contribute to symptomology due to the lack of UBE3A expression (and others such as GABR genes) in the brain. Research performed under the banner of Pillar 3 includes all advancements made to address these downstream targets and, in this week’s newsletter, we will feature Dr. Brenda Vincenzi’s Roche update from the 2022 FAST Science Summit on the use of Alogabat in a Phase 2a Angelman syndrome clinical trial.

In her talk, Dr. Vincenzi discussed how AS individuals with the deletion genotype generally present with greater impairments likely due to the loss of additional genes, such as GABR, beyond just UBE3A. GABR genes code for GABA_aɑ5 receptors which are important in brain development and function and are linked to many neurodevelopmental disorders and epilepsy. To restore deficient GABAergic signaling, Dr. Vincenzi and her team are utilizing Alogabat, a GABA_aɑ5 positive allosteric modulator, that is taken orally once a day and shows acceptable safety margins. They are currently in a Phase 2a open label clinical trial to investigate safety and proof-of-mechanism in children and adolescents with AS deletion genotypes. If effective, they hope to observe improvements particularly in cognitive and seizure measures.

To see more, watch the full video here:

Pillar 3 of the FAST Roadmap to a Cure 2.0 consists of therapeutic programs which focus on “downstream targets to treat symptoms” by addressing different molecular pathways and effector proteins impacted by the missing UBE3A protein.

Currently, we have four programs in the pipeline under Pillar 3 and one active human clinical trial:

• Exogenous ketone supplements
• GABA_aɑ5 positive allosteric modulator (Alogabat)
• IGF-1, 2 ligands (NNZ-2591)
• BDNF

Click here to learn more about each of these programs:

FAST Spain’s Chairperson, Domingo Delgado, submitted a video with his daughter, Carla, who lives with Angelman syndrome, to the Department of Transport of the Community of Madrid’s "We are On-Line with You" campaign at the end of 2022. The workers of Metro de Madrid voted it as one of their favorites!

As a result, FAST had 26 days of visibility along Madrid’s subway Line 10 (blue line) to bring awareness to the organization and what we are doing. What a creative and attention-grabbing way to bring awareness to Angelman syndrome. Thank you so much, FAST Spain!

Learn more by clicking here or below:

In just 2 weeks, around the world, the community will come together to bring awareness to Angelman syndrome for the 10th annual International Angelman Day! FAST is excited to participate alongside more than 50 organizations worldwide for this celebration.

To bring a fun twist to this significant day, we created an opportunity for community members to share one “#MomentOfHope” — a distinct experience with your loved one with AS that gave you hope and energy to fight for a cure. There are already a bunch on the page! Go visit and add your own….

“My moment of hope was when my wife, Mercedes, called me at work to tell me something Izzie Mae had done. Her voice was almost frantic as if she didn't know exactly what to make of it. She was helping our neurotypical four year old, Willa, spell her name with alphabet magnets on our refrigerator. When Mercedes told Willa to find the “A” magnet, Izzie Mae, who was watching closeby, reached into a large pile of letters and handed an “A” to Mercedes. 

Izzie Mae's teachers had shared encouraging progress stories with us before, but for her to display this at home was a major moment of hope. She truly takes in and understands so much. It motivated me even more to push for a cure so we can unlock all of the knowledge and gifts within her!”

- Easton, father of Izzie Mae

Share your Moment of Hope on our website and check out all the submissions from the FAST community:

We’ll be sharing these Moments on social media leading up to International Angelman Day!

As our community fundraising efforts are underway, we want to remind the community that FAST is proud to be the only US-based Angelman syndrome organization that has the highest ranking on Charity Navigator, the 4-star rating! 

Learn more about Charity Navigator and while you are there, see if your employer offers a company match or paid volunteer hours, to support your 2023 CAN fundraising goals!

You can learn more about Charity Navigator on their website:

Did you share your Moment Of Hope on our site? We can’t wait to see yours!

As always, please share this link with anyone who would be interested in receiving our updates.