Seven lessons I’ve learned from Rett syndrome

Mom and Ava

By Joanne Gryniewicz

As a mother of a child with Rett syndrome, a disability that affects the brain’s ability to plan or coordinate motor skills, the phrase “take for granted” takes on a whole new meaning. I cannot take for granted that Ava can recite her A, B, C’s or feed herself a snack or go to the bathroom on her own. Quite the opposite. Every day, I strive to properly appreciate the effort it takes for Ava to perform the most mundane tasks. I am the one being “schooled” on Rett syndrome.

Here are seven of the things Rett syndrome has taught me:

1. Technology is seriously cool. 

Ava doesn’t speak, but she can communicate. She uses a speech-generating device with eye-gaze technology that detects the box or symbol she is looking at on the screen and speaks the words it represents. The grid of symbols represent everyday activities, needs, expressions and feelings. It has been invaluable to be able to hear Ava’s “voice.” She navigates with so much ease it’s scary.

2. How to adapt.

Rett girls engage in a stereotypical hand movement, like a hand-washing or wringing that renders their hands useless. You can break the pattern temporarily — hold one of her hands and she will focus on using the free hand to lift a fork to her mouth. But inevitably, the fork will be dropped as she tries to find that other hand. If she had hand use she could learn sign language. She could dress, feed, bathe and toilet herself. Yeah. This one hurts.

Ava gets a hug from big sister, Zoe

Ava and big sister, Zoe

3. Patience.

Rett syndrome’s most profound disability is apraxia, or the inability to carry out a cognitive intent. Ava needs anywhere from 10 to 18 seconds to respond to your request. That’s a LONG time to wait. Ask her to make a choice between cereal and fruit for breakfast and you can see the anxiety build on her face. I’ll take any queue as a response. She may separate her hands temporarily to reach out and indicate her choice, or stare it down like a child possessed. My favorite is the full on rushing tackle. Cereal it is.

4. How to deal with bizarre symptoms.

Ava holds her breath. It freaked me out the first time it happened. Ava turned blue and I screamed for help. Now it’s just part of daily living. She holds her breath. Constantly. An awful side effect of breath holding during meals is swallowing air. Awful because all that air gets trapped in her colon and her belly. Her belly swells by the end of the day until she looks like she swallowed a beach ball.

5. How to deal with bizarre symptoms, part two.

Bruxism, also known as teeth-grinding. Like fingernails to a chalkboard. We hear it ALL day. The harder Ava concentrates, the louder and more intense it gets. Makes my eyes water. I give her a hug, tell her to take her time, and she relaxes and lets go.

Ava and Zoe wearing cowgirl hats

6. The need for respite.

I never heard of that word until our social worker mentioned it as an offered service. A provider will care for your child while you… rest. On any day, take note of how many times your child feeds themselves a snack, goes to the bathroom on their own, dresses themselves, plays with a toy or engages in a conversation. Ava needs assistance with every one of those tasks. Imagine how that adds up in a day. We are so blessed with nanas, papas, grandpa and a rock star nanny to offer us these tidbits of time.

7. In the end, she’s just a kid.

Ava is all about the party — she even has a party dance. She’ll rock side-to-side shifting from one foot to another. Then the party really gets jumpin’ and Ava shifts to over-stimulation mode. Now she’s rocking forward and back. That’s when we know it’s time to dial it back. She never loses it though. As long as there are other kids around — laughing, dancing, chasing siblings — Ava knows she’s part of something fun.

Ava dancing with Zoe

Source :

Anavex awarded grant to fund clinical trial of Rett syndrome drug


Anavex Life Sciences Corp. will receive funding for a phase 2 trial of its Anavex 2-73 drug from the International Rett Syndrome Foundation to study the rare neurological disorder, the company announced early Thursday.

The $600,000 grant, which will fund the majority of Anavex’s AVXL, -0.71%  clinical trial, will be the fifth clinical trial for Rett syndrome funded by the foundation and underway this year. Other biotech companies with funded trials include Neuren Pharmaceuticals Ltd. NEU, +8.20%

Rett syndrome is a rare condition affecting about one in 10,000 girls that’s caused by a mutation on the X chromosome. Symptoms include motor and cognitive impairments, seizures and anxiety, and many of those affected die young.

Many in the Rett syndrome community are looking in the long term to gene therapy for a treatment. But having a drug that works across the broad spectrum of symptoms — as opposed to taking medications for each one — is a more near-term goal, said Gordy Rich, the Rett foundation’s chief operating officer.

Rich is also a Rett parent. The prospect of a more comprehensive medication for his 22-year-old daughter is “life-altering,” he said.

“When my daughter was diagnosed there was no known cause and no known cure,” Rich said. Five clinical trials being underway means “to all parents, this is really the most incredible time… We’ll have options for our girls that can improve their quality of life.”

Anavex 2-73, which was designated as an orphan drug for Rett syndrome last spring — which grants companies developing rare diseases various development and commercial incentives— may have that potential.

The 12-week trial — which will cost about $1 million total and enroll between 50 and 80 patients — will measure the drug’s effect on seizure reduction, cognitive impairment, mood disorder, autistic behavior and anxiety, Christopher Missling, president and chief executive officer of Anavex, told MarketWatch.

The drug was selected based on its results in mice, where it addressed a number of symptoms, Rich said.

“To us that’s very exciting, and we want to move as many of the compounds into clinical trials so we can get treatments on the path to a cure,” he said.

The trial is expected to begin this year, with data possibly coming out by the end of the year, Missling said.

Anavex’s relationship with the foundation will also assist in enrolling patients in the trial, which should help hasten trial results, he said.

Anavex 2-73 is also being tested in other areas, including Alzheimer’s disease, Parkinson’s disease, autism and more.


Ed Sheeran serenades young fan with Rett Syndrome at Epsom Hospital

Ed sings to Melody and her parents

By  Craig Richard

A brave young girl living with a rare condition was serenaded by her musical hero at her hospital bedside today.

Nine-year-old Melody Driscoll has Rett Syndrome, a condition that affects brain development and causes physical and mental disability, and is often an inpatient on Casey Ward – the children’s ward at Epsom Hospital.

During long stays in hospital there’s always one thing certain to brighten Melody’s mood – flame-headed singer-songwriter Ed Sheeran.

Her parents launched a campaign for her to meet Ed, and today (Wednesday, November 9), he obliged.

Epsom Guardian:

Ed signed Melody’s pink guitar before treating her to two of his hits, Thinking Out Loud and Photograph, before posing for snaps and meeting other young inpatients.

Dr Ruth Charlton, Consultant Paediatrician and Joint Medical Director, said: “We are so touched that Ed would take the time out of his busy schedule to visit Melody and the other young patients on the ward.

“Melody was mesmerised by Ed, and it was a truly wonderful to see how happy he made her.

“We would like to thank Ed for coming – this was a very special day for our staff, our patients and of course, Melody.”

Epsom Guardian:

Melody’s mum Karina, (pictured above with Dr Charlton and Ed Sheeran), who launched the campaign, said: “Melody absolutely loves Ed’s music, and his lyrics mean so much to us as a family. It was amazing to meet Ed, and everyone could see just how impressed Melody was – she even got hugs and kisses from him!

“We joke that Ed is Melody’s boyfriend because she is so taken with him, and now that she’s met him in person a dream has come true.

“Ed’s music and the staff here, including Melody’s consultant Dr Tim Marr, have kept her alive.”

Ward Manager Karen Kilday, said: “It was wonderful to see Ed on the ward and to see the joy that it brought to Melody. His caring and relaxed approach were evident to see and everyone on the ward that day will remember the visit and this lovely moment forever.”



Study reveals possible ‘dimmer switch’ drug for Rett syndrome


Researchers at Vanderbilt University Medical Center have relieved symptoms in a mouse model of Rett syndrome with a drug-like compound that works like the dimmer switch in an electrical circuit.

The finding, reported this week in the journal Human Molecular Genetics, suggests a potential new way to treat the rare neurodevelopmental disorder, which occurs predominantly in females, as well as more common forms of autism spectrum disorder.

Further study is needed before this approach can be tested in patients, but animal work from other groups suggests that symptoms in Rett syndrome are reversible, said senior authorColleen Niswender, Ph.D., associate professor of Pharmacology and director of Molecular Pharmacology in the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD).

Rett syndrome patients exhibit a constellation of symptoms, including verbal and nonverbal communication deficits, difficulty walking, progressive developmental regression, epilepsy and intellectual disability. The hallmark symptom is repetitive hand movements such as wringing, washing, clapping or tapping.

Most cases of Rett syndrome occur spontaneously from random mutations in the MECP2gene, which results in disruptions in neurotransmission, including signals mediated by the excitatory transmitter glutamate. A related genetic disorder, termed MECP2 Duplication syndrome, results from overexpression of the MeCP2 protein and is found predominantly in young boys.

The researchers used a mouse model in which MECP2 was “knocked out,” resulting in Rett syndrome-like symptoms. Expression of the metabotropic glutamate receptor 5 (mGlu5), which is important in transmitting nerve signals in the brain, was reduced in brain areas of these mice.


The investigators also found reduced levels of mGlu5 expression in autopsy samples from the brains of Rett syndrome patients, suggesting that the animal work may translate to the clinical population.

They then tested a compound, developed at Vanderbilt, called a positive allosteric modulator or PAM that, like a dimmer switch, “turns up” the activity of mGlu5 when glutamate binds to it.

Animals treated with the compound showed improved motor performance and reduced Rett syndrome-like symptoms, including repetitive clasping of their hind claws.

Previous studies have suggested that enhancing excitatory neurotransmission may increase an already high risk of seizures in Rett patients, but in the current study, seizure occurrence did not increase, even after multiple weeks of chronic dosing with the PAM.

This may be because the compound acts on only a subset of mGlu5-mediated signaling pathways, leaving others unaffected.

“Our work demonstrates that potentiating the activity of mGlu5 can rescue several deficits commonly found in mouse models of Rett syndrome,” said the paper’s first author, Rocco Gogliotti, Ph.D., a postdoctoral fellow in the VCNDD.


“Importantly, by integrating recent advancements in mGlu5 pharmacology into the drug development process, we were able to test the efficacy of our novel compound in a mouse model without observing negative side effects, such as seizures, that have been historically associated with this target,” he said.

Disease progression – and mGlu5 expression – change through time in MeCP2-deficient mice. “A very careful dissection of the time course of the disease is required before modulators of excitatory transmission can be advanced to clinical studies,” Niswender said.




Insights into neurons that cause symptoms of Rett syndrome could guide new therapy search

Two studies in mice from Baylor College of Medicine, Texas, reveal new insights into neurons that mediate symptoms typical of the postnatal neurological disorder Rett syndrome.

Rett syndrome is a childhood disorder that typically manifests after the first birthday. Early symptoms include delayed development and poor coordination while, during the second stage, a child will gradually or suddenly develop severe problems with communication, language, learning, co-ordination and other brain functions. It can cause seizures, breathing difficulties and sometimes premature death.

Rett syndrome is caused by mutations in the MECP2 gene which makes a protein with a similar name, MeCP2, that is essential for proper function of neurons in the brain. When MeCP2 is missing from all cells, mice develop symptoms similar to those seen in Rett syndrome and male mice die prematurely.

The two major types of neurons in the brain are excitatory neurons, which send signals to other neurons telling them to be active, and inhibitory neurons, which stop or dampen the activity of other neurons to control the timing and rate of incoming information. These neurons must act in balance with each other for the brain to work correctly, otherwise disruptions can lead to the onset of neurological disorders.

One study in mice, published in the journal eLife, shows that expressing MeCP2 only in inhibitory neurons increases lifespan and rescues most but not all behavioral deficits.

A second study, published at the same time in eLife, shows that removing MeCP2 only from excitatory neurons in mice contributed to the onset of several Rett-like symptoms, some of which are distinct and complementary to those mediated by inhibitory neurons.

“Together, our findings show that rescuing the activity of MeCP2 in certain cell types can have a profound effect on improving symptoms,” says Huda Zoghbi, senior author of both papers and a recent winner of the Shaw Prize for her research leading to the discovery of the gene causing Rett syndrome.

Approximately one in every 10-12,000 females are affected by the disorder, while it is much rarer in males who have more severe symptoms and die early in life. The two studies showed that MeCP2 is important for both inhibitory and excitatory neurons in terms of motor function and survival, but also revealed that each type of neuron is key for distinct neuropsychiatric features.

For the first study, the team asked if expressing MeCP2 in inhibitory neurons, while the gene remains missing from the rest of the body, would be enough to prevent some or all of the symptoms seen in the Rett syndrome mouse model.

“Our data suggest that when a brain is missing MeCP2 everywhere, turning on the gene in inhibitory neurons can make the brain network nearly normal and prevent most Rett-like symptoms,” says Kerstin Ure, Postdoctoral Fellow and lead author of the study.

“However, when both normal cells and cells with mutated MeCP2 are present in the same brain, as seen in female mutant mice, the abnormalities caused by this mixture cannot be overcome just by rescuing the function of inhibitory neurons. This highlights the importance of doing future studies in female mice to better understand how Rett syndrome develops.”

Taking these new insights into account, the authors of the second paper set out to learn what aspects of the syndrome would appear or recover if MeCP2 was removed or re-expressed in excitatory neurons.

“We showed that mice lacking the gene from these neurons develop tremor and anxiety-like behaviors, abnormal seizure-like brain activity, severe obesity, and early death, which is surprisingly different from mice missing MeCP2 in inhibitory neurons,” says Xiangling Meng, a neuroscience graduate student at Baylor College of Medicine, and lead author of the second study.

“When the gene was re-expressed in excitatory neurons, the female mice were almost completely recovered. In the case of more severe males, their anxiety and tremors were rescued, suggesting that impairment of excitatory neurons by removing MeCP2 contributes to the onset of specific symptoms such as these.”

The team believes the next steps will be to investigate if drugs that improve the function of both inhibitory and excitatory neuron activity can be used for treating patients with Rett syndrome. Further studies will be focused on improving the function of these neurons in the hope of restoring the balance between them.

Zoghbi adds: “For now, we are looking at different ways of activating inhibitory neurons in the female mouse brain, including testing drugs and special channels that can activate a cell when a specific chemical is given to the mice. We hope these methods will help us refine a path forward for potential new therapies for patients.”



The papers ‘Restoration of MeCP2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett Syndrome’ and ‘Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders’ can be freely accessed online at and Contents, including text, figures, and data, are free to reuse under a CC BY 4.0 license.

Senior author Huda Zoghbi is also Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, a Howard Hughes Medical Institute Investigator, and Professor of Molecular and Human Genetics at Baylor College of Medicine.

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