Roadmap to a Cure

OVERVIEW Imagine if your child, or a loved one, could not walk or speak and had Angelman syndrome is caused motor impairment, debilitating seizures and a sleep disorder. This is by a loss of function in the life today for many of the nearly 500,000 people living with Angelman UBE3A gene on the maternal syndrome (AS). But it doesn’t have to be that way. Scientists have shown 15th chromosome, which that these devastating symptoms can be reversed, and FAST (Foundation prevents the body from producing enough UBE3A for Angelman Syndrome Therapeutics) has a plan well underway to protein. It’s a relatively simple achieve just that. We are finalizing the scientific foundational work disorder because it involves only necessary to test therapies in human clinical trials. Please take a moment one gene, and we have multiple to read on and learn how our Roadmap to a Cure will change the lives of options for treatment. people with Angelman syndrome and, potentially, millions more who have related disorders like autism and Alzheimer’s disease.

FAST’s Roadmap is focused on three strategies to treat Angelman syndrome. AS is not a degenerative disorder, and these approaches, which have already been tested in animal models, are believed to have the potential to reverse the effects of the disorder in children, teens and adults.

Route 1 Route 2 Route 3 Gene Therapy Gene Activation Therapy Downstream Therapy People with AS have a mutation, People have two sets of chromo- Downstream therapy uses drugs deletion or other defect in their somes – one inherited from the to treat the symptoms of Angel- UBE3A gene. Gene replacement mother and one from the father. In man syndrome and improve the therapy uses safe viruses to deliver a typical person, the maternally quality of life for individuals with healthy copies of the UBE3A gene inherited UBE3A is active, while the disorder. There are many drugs into cells to replace the missing or the copy of the gene inherited that are already approved by the underperforming gene. The goal is from the father is silenced in the FDA that might be useful for treat- for the body to start making the neurons in our brains – a phenom- ing Angleman syndrome. Finding UBE3A protein that is deficient or enon known as imprinting. For these drugs and showing that they absent. A few gene therapy treat- individuals with Angelman can be repurposed would be the ments have already been approved syndrome, the maternal gene does fastest way to bring new treat- in Europe for rare disorders (e.g., not function properly. The goal of ments to the Angelman communi- Strimvelis), and many gene thera- gene activation therapy is to turn ty. The U.S. Food and Drug Admin- py trials are underway in the on the normally silent paternal istration (FDA) established a Rare United States for a variety of disor- gene so there is an active copy Disease Repurposing Database ders (e.g., Batten disease, San Filip- producing the necessary UBE3A containing drugs found promising po syndrome). protein. or already approved for treating rare diseases.

FAST CureAngelman.org Phone: 630.852. FAST (3278) P.O. Box 608, Downers Grove, IL 60515 Email: [email protected] Fax: 630.852.3270 So little seems to stand in the way of a cure for Angelman syndrome. The FIRE team’s efforts are gaining significant attention. The Marnier- The FAST track: from bench Lapostolle Foundation recently awarded a $5.8 million grant to FAST to to bedside. FAST is the largest non-govern- help fund the remaining foundational laboratory tests necessary to bring mental funder of Angelman the knowledge gained by FAST researchers to the next stage: human syndrome research and the only clinical trials. This gift is the largest private grant ever made to Angelman organization with a detailed plan towards a cure. While research. Inspired by a family member who has a child with the disorder, others said a cure was not the Marnier-Lapostolle Foundation conducted an intense and highly possible, FAST spent the past competitive review process before investing their money in FAST. seven years strategically investing millions of dollars in The family that created Grand Marnier founded the Marnier-Lapostolle research to lay the foundation Foundation. for scientific breakthroughs. Recent advancements in the understanding of Angelman Now is the time for action. FAST’s Roadmap to a Cure for Angelman syndrome, made by FAST scien- syndrome is bold, ambitious, and, with your help, achievable. The tists, suggest finding a cure for Roadmap costs an estimated $20 million dollars, and AS families have this disorder in the near future is been challenged to raise $2 million of that investment. We are calling on not only possible, it’s inevitable. everyone connected to a loved one with Angelman syndrome to support Brightest minds partner in race this research. Please join us by making a financial gift, spreading the word to cure Angelman syndrome with friends and family members, and fundraising to help us cross the FAST brought together a multi-disciplined team of more finish line. Your efforts will take us one step closer to making therapeutics than two-dozen scientists from available to those affected with AS and, ultimately, finding a cure that top research universities and will free our children. pharmaceutical companies to join forces on a focused path to a cure. Known as the “FIRE” ABOUT FAST Consortium: FAST Integrative FAST is a 501(c)(3) nonprofit research organization. Research Environment, FAST’s scientists know exactly what Paula Evans, an Illinois mother whose daughter was causes Angelman syndrome. diagnosed with Angelman syndrome, founded They have cured the symptoms FAST in 2008. FAST raises money to fuel of the disorder in mice using cutting-edge research and takes an several strategies. active role in drug development to treat, and ultimately To learn more about cure, the disorder. FAST’s FIRE team, visit CureAngelman.org/FIRE.

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