Why there is Hope for a Cure

Why we need money for a cure

How much money will it take?

Why There is Hope for a Cure

If we could put 15 to 20 million dollars into Angelman Syndrome research NOW, we could fast track the discoveries towards potential therapeutics and be able to support pharmaceutical development and clinical trials.

To put this into perspective, companies spent 3 million dollars for a 30 second slot in the 2011 Super Bowl6. We don't need a tremendous amount of money; we simply need it soon.

Loss of UBE3A does not appear to affect neuronal development. Why is this important?

FAST Funded Science

Is there any evidence that restoring UBE3A function would allow neurons to function better?

The approach is straightforward; the goal is simple.

What we are lacking are the resources to get these strategies into place. In 2010, the National Institutes of Health spent less than $500,000 on Angelman Syndrome Research. That is less money than is required to run a single small research laboratory for two years. Because Angelman Syndrome is a rare disorder, it has been difficult to recruit large numbers of researchers to our cause, as they have few sources to turn to in order to acquire funding for this type of work. The money we raise at FAST will go straight to research directed at finding a therapeutic that will restore function to neurons in those affected with Angelman Syndrome. With money, we can recruit new researchers and provide needed funding to those already dedicated to Angelman Syndrome research. With money, a cure is only a heartbeat away.

By raising awareness and funds, we will put the resources into the hands of the researchers who are best positioned to bring a therapeutic for Angelman Syndrome into reality in the laboratory. Once the groundwork is completed, we will lobby pharmaceutical companies to develop this needed therapeutic with the knowledge they need in hand.

Angelman Syndrome affects only 1-10,000 to 15,000 people so there aren't as many people lobbying for research funding specifically for Angelman Syndrome as there are for more common disorders such as autism. Additionally, since Angelman Syndrome is rare, pharmaceutical companies are not in a position to invest time and funds into developing therapeutics that would have a limited market and thus, not be able to recoup their investment. But that is where FAST comes in.

Yes!

Mice that lack UBE3A function in the brain display many features of Angelman Syndrome including learning difficulties, balance and movement disorders, and seizures.

Will this benefit anyone else?

Research indicates that the brain and the neurons form correctly in an individual with Angelman Syndrome. This is a critical piece of information because it indicates that the neurons could function normally if UBE3A function could be restored. As an analogy, if we think of the brain as a car engine, the brain of an individual with UBE3A has all the pieces and parts in the right places. Nothing is missing. However the engine runs poorly since it can't be properly tuned. UBE3A appears to act as a tuning mechanism to allow a neuron to function at its fullest potential.

How long will this take?

Research on the causes and potential treatments for Angelman Syndrome only occurred recently. The research showing loss of UBE3A was responsible for Angelman Syndrome was published in 1997.

We believe that with the right infusion of funds into Angelman Syndrome research, we could have a therapeutic within 10 years if not sooner.

Ten years later, Angelman Syndrome was cured in the mouse model, and research has progressed rapidly from this point. But Angelman Syndrome is rare. Many people have never heard of Angelman Syndrome. Many parents find that doctors have never heard of Angelman Syndrome!

Curing Angelman Syndrome would open a gateway for curing other neurological disorders including autism and Alzheimer's disease. A therapeutic for Angelman Syndrome will teach us about how neurons function and learn; knowledge required to restore function to a brain damaged by injury, stroke or disease. It may also provide therapeutic strategies to increase neuronal function in similar disorders such as Rett Syndrome and Fragile X Syndrome.

Research has shown that modifying other genes products in these mice can alleviate all of the symptoms of Angelman Syndrome!

This research showing rescue in the Angelman Syndrome mouse model was recognized as groundbreaking in the field, and selected as a Neuroscience Highlight of the Year in 2008.

More recently, work in Dr. Edwin Weeber's lab has found that restoring a functional UBE3A protein into the neurons of adult mice with Angelman Syndrome can rescue the learning defects and balance and movement disorders as well. This suggests that if we could restore UBE3A function in the neurons of children with Angelman Syndrome, they too could see improvement or rescue of their symptoms.

If it is so easy,

why hasn't it been accomplished by now?

We know what is wrong in Angelman Syndrome - the function of one gene, UBE3A, is missing.

We know that loss of UBE3A does not affect neuronal development, only neuronal function.

We have excellent animal models for Angelman Syndrome, and research has indicated that Angelman Syndrome can be cured in those models.

We have strong ideas and approaches for restoring UBE3A function in neurons.

Why is it an advantage that Angelman Syndrome is caused by defects in one gene?

Are there real possibilities of restoring UBE3A in the neurons of individuals with Angelman Syndrome?

In order to cure any disease or disorder, you have to know what has gone wrong in the body and what you need to do to fix it. In the case of Angelman Syndrome, we know what has gone wrong. The gene product UBE3A is not produced in neurons in the brain. Without UBE3A, the neurons can't function correctly. Because of this, individuals with Angelman Syndrome have severe difficulties with learning and with the use of their bodies. Because the neurons can't function well, these individuals lack the ability to speak and have life- debilitating seizures. But all of the symptoms of Angelman Syndrome come down to loss of the function of one gene in the genome; UBE3A. Because we know exactly what is wrong in Angelman Syndrome, we know what to focus on to find a therapeutic - something that will restore UBE3A function to neurons. Compare this to disorders such as Autism, Schizophrenia or Alzheimer's Disease where we still don't know what has gone wrong despite the vast amounts of money spent on research in these areas.

There are clear strategies for restoring UBE3A itself, or the functional equivalent of UBE3A in neurons.

One strategy is to resupply UBE3A itself to neurons that need it. While this sounds complicated, in individuals with Angelman Syndrome, this may be astonishingly simple. Everyone has two copies of the UBE3A gene, one from their mother and one from their father. But due to a developmental quirk, we only use the gene we inherit from our mothers. The majority of individuals with Angelman Syndrome either have deletions that remove the mother's copy of UBE3A, or have mutations that prevent the mother's supplied UBE3A gene from being functional. But each of these individuals has another copy of the UBE3A gene that isn't being used. Thus, one of the easiest strategies would be to find a drug or other method to turn on the normally silent UBE3A gene inherited from the father. Current researchers have found that the father's UBE3A gene can be turned on to small degrees in different experiments. Thus under the right conditions, neurons can turn this gene on. We just need to find the right drug or treatment to do this to a larger sustainable degree.

A second strategy is to find a way to restore neuronal function by correcting the issues caused by lack of UBE3A. For example, in the mouse model for Angelman Syndrome, the learning and motor planning issues caused by loss of UBE3A can be compensated for by including another gene product (CaMKII) in a form that is more active than usual. Thus if we can find drugs or strategies to enhance CaMKII activity in neurons, this would also benefit individuals with Angelman Syndrome. Other potential targets that could compensate for loss of UBE3A also exist. We just need to be able to test for ways to enhance these targets in individuals with Angelman Syndrome.

Be part of a miracle in your lifetime.

Everyone uses the word "cure".

What makes this situation different?

Support FAST and our goal of finding a cure for Angelman Syndrome.

We all know that saying you want to "cure" something is the way most disease foundations raise money for their causes. In our case, there is a real chance to cure Angelman Syndrome now, as outlined above. We know what is involved. The research suggests that this can be done. And we have real ways to accomplish this goal from a scientific standpoint. The only thing standing between individuals with Angelman Syndrome and a cure is money.

www.cureangelman.org

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