GNAO1 Stories

Rare disease charity funds $48,000 in CRISPR research at Michigan State University

Wednesday, June 13, 2018

East Lansing, MI – The Bow Foundation today announced a grant of $48,000 to the Michigan State University Department of Pharmacology & Toxicology. The grant will expand research into a rare genetic disorder with no common name.

The research project will be led by Dr. Richard Neubig, Chair of the Department of Pharmacology & Toxicology in the College of Osteopathic Medicine. It will use revolutionary CRISPR technology to create mouse models to study GNAO1-related neurodevelopmental gene mutations. Through the study, researchers will gather more information about GNAO1, test existing drugs, and identify possible new treatment options.

Roughly 70 children worldwide are currently known to be impacted by a GNAO1-related neurodevelopmental disorder. Children with the disease suffer from severe developmental delays, seizures and uncontrolled muscle movements.

“Dr. Neubig’s research gives the promise of hope to the dozens of GNAO1 patients around the world,” Bow Foundation co-chairs Emily Bell and Alice Fox said in a statement. “By helping the medical community better understand the impact of GNAO1-related neurodevelopmental disorders, it could also open doors to better treatment options for patients. We’re excited to fund this new research project and are thrilled to be working with Michigan State. We look forward to gaining new insights and funding additional studies as we work to increase GNAO1 awareness and change lives.” 

The Neubig lab will develop mice that carry two of the more common GNAO1 mutations. Researchers will analyze the development of these mice and undertake preclinical therapeutic trials with existing drugs to identify new options for controlling GNAO1 neurodevelopmental symptoms in human patients.

“We look forward to working with the Bow Foundation to better understand the consequences of GNAO1 mutations on child brain development and to try to identify new therapeutic options,” Dr. Neubig said. “Their support of families of children with this rare disorder and their support of research to help these children makes a huge difference.”

This is the second major Bow Foundation medical research grant. The foundation previously funded a $100,000 GNAO1 stem cell research study at the University of Virginia’s School of Medicine.

The Bow Foundation is a non-profit dedicated to supporting GNAO1 families through enhanced research and increased awareness. The foundation was launched in April of 2017 by two families who have children with a GNAO1 disorder. Visit www.BowFoundation.org to learn more or donate. 

Emiliana`s  Story – Learning about Resilience

Written by: Emiliana’s Mom Natalia

I had never known what resilience was until I met Emi, my little daughter.

She was born in October, 2010 almost 2 months earlier than expected.  I remember she was a little baby in the Neonatology Box, sleeping without her mummy.  It seemed she was there without any fear, trying to remove the feed tube of her nose.  A nurse told her, “Emi if you remove the tube, you will have to be fed by your mum.”  She did not have enough strength to suckle. And I had just had a surgery and did not have enough milk for feeding her but finally she managed to remove the tube, I was terrified, then the little baby looked me directly to my eyes making contact, and opened her mouth: the sweet link between a mother and a daughter had begun.

That was the first time Emi taught me about resilience.

Our first year was normal, like others families, until she was 6 months in when our pediatrician started to suspect something. Emi was not achieving the average skills for a baby of her age.  That was the time we met our first neurologist. They said she has hypotonia, and motor development delays, they did not know if she would walk, or talk. Even worse they did not know what was causing that.

We began a long, long journey, a lot of medical consultants, a lot of therapies, a lot of people coming and going looking for her diagnosis, looking for her treatment, fighting against the Medical Insurance, fighting against everything, even against ourselves that were in the middle of the process of accepting what was happening. We are 6 years later and the journey still goes on.

It was not easy but at the same time you have the opportunity to discover a new world, to be a special parent (a parent of a kid with special needs).  My little princess always showed her strength, never complained when she was examined, when she was put to a new and sometimes painful or invasive treatment and when she had her therapies.  She never complained, she did it, always with a smile and good vibes.  In the process, the people who met her, started to fall in love with her.

The long stay in the Hospital

The last three years Emi had had some episodes difficult to explain. Orofacial dyskinesia, a type of mouth`s involuntary movement. It used to happen very shyly and it took 2 or 3 days, no more. At the beginning something imperceptible, however each episode was longer, and more intense.

I remember those days but none of our doctors were worried, and even when we flew to Rochester, NY to see an expert in movement disorders (Dr. Jonathan Mink) he told us that these kind of involuntary movements were a symptom of something like fever that is triggered or sometimes when she is dealing with an infection, anxiety or stress.  We could deal with it; it was not our main issue.  So, we forgot about those episodes and we put our energies in giving Emi all the opportunities for improving her motor skills.  Speech therapies, OT, motor therapies, horse therapies, assistive technologies and equipment’s.  In parallel we continued looking for her diagnosis, the cause of those symptoms, we send samples to everywhere, we made queries with specialists in Spain, US and Japan.  We discarded a high number of possible diseases at that time we did not know the name of the “monster”.

In August 2016, after a gastroenteritis she displayed those movements again, but this time they took longer, and they were stronger.  One week later she was in the ICU drug induced coma, mechanical ventilated. The violent involuntary movements migrated from her mouth to her limbs.

My husband and I did not understand anything.  Our hearts were broken seeing her.  What was happening? Come on monster, show your face!

They tried several neurological drugs for almost 2 months, but nothing worked.  I learned to count the number of sedatives rescues she used to receive to measure the level of her crisis.

In parallel and with the help of good people we managed to send blood samples to South Korea and the US, to have a new test done, a Whole Exome Sequencing, essentially a mapping of her DNA that would detect every mutated gene that could be the possible source of the symptoms.  At that time, genetic disease means that we would put a name to the monster, but we could not give her a cure, only relief for her symptoms and look for other cases in the world.

2 days before her birthday, October, 25.  The number or rescues started to decrease and finally she opened her eyes smiling as usual, recognizing her brother Mateo.  She went through cycles.  She was in ICU and every intra hospital virus triggered the crisis again.  We were stuck.  Our neurologist gave us a new article about a gene called GNAO1 which mutations were linked to some types of epilepsy. But recently a few cases (6 the article said, only 6 in the whole world) with children with severe involuntary movements were detected to have the same mutated gene. The same article said that the crisis was highly resistant to any pharmacological treatment.  We had tried almost everything.

Resilience

To fight for her was our duty.

We started research and found a medical article in where it was described a little girl in Turkey with the same mutation, that had underwent a surgery called Deep Brain Stimulation. A surgery usually for Parkinson. There was not much experience with cases like ours, or with young kids.
It was also the option that our neurologist had in mind, so she made and inter-consult to the referents in this procedure, Dr. Jean Pierre Lin, from The Evelynda hospital, in London.

We spent the Christmas in the hospital, we made a Christmas tree in her room, at that point, 4 month later, we were a family there.  On January 4th,2017 Emi underwent surgery, deep brain stimulation, first case with her condition in Argentina.  Several neurosurgeons and other members of the team were part of the procedure. The surgery took 11 long hours.

They turned on the stimulator two days later, at midday on a very slow setting, that night Emi received the last rescue medicine.  They started to decrease the level of sedatives, slowly, day by day.

4 weeks later our brave girl was discharged of the ICU without any crisis.

Unfortunately she was operated again 4 months later due to a staph infection, at beginging of August.  We camped in the hospital for almost a year.

There is a song is Spanish that say ” me pasaron tantas cosas, que no me acuerdo de nada” So many things happened to me, that I do not remember anything. This entire long journey would be summarized by that phrase.

Now Nov 2017 we are backed home. Emi is doing well and we are on track again in our long journey of giving her all the opportunities to sort her motor issues.  She may walk one day, she may talk one day.  We do not know but we work pursuing these goals every day.

THE GNAO1 Family and the BOW Foundation

During the stay in hospital and as soon after we were told about Emi´s diagnosis, we found on the Internet (Facebook) the few other families with the same genetic disease. For the first time our condition was not rare for some people, for the first time we did not feel alone anymore.
At that time there was a family in the US struggling with the same situation as us, and some nights we exchanges messages, from ICU to ICU.

In my case, close to the surgery date, as soon as I found the other families, we had the opportunity to hear their testimony and ask them about every step of her recovery. I knew Deep Brain Stimulation was totally new for the cases like Emi´s, but I could hear the others testimony, and it had worked for other kids, I knew it may work for my daughter.

Now, looking back, one year later, we understand that we had luck, to put our daughter in the best and expert medical hands we have ever could.

Along the process we touched base with the Bow Foundation, doing great things for the GNAO1 awareness, supporting the families and fundraising for research.

We are working on understanding this disease just discovered, and in consequence to find a cure in the near future. But we also are pursuing to make awareness for an earlier Diagnosis and intervention.  There are several kids suffering for the same illness without the possibility to receive at least a treatment for the symptoms. They are just kids.

So, you have reached us, and now you are part of our family. Your support is very important for us.

Thanks for being with us during this long journey. We will continue together as a Gnao1 family, pursuing the same goals.

Bow Foundation to host inaugural GNAO1 medical conference

Washington, D.C. – The Bow Foundation will host a first-of-its-kind medical conference in our nation’s capital on Monday, November 13. Families from around the world will meet with doctors and researchers about GNAO1, a rare genetic disorder with no common name.

Roughly 60 children worldwide are impacted by a GNAO1 disorder. Children with the disease suffer from severe developmental delays, seizures, and movement disorders.

“This conference gives us a great opportunity to foster new relationships, discuss shared experiences, and engage the medical community in a conversation about treatment and research opportunities,” Bow Foundation Co-Chairs Emily Bell and Alice Fox said in a statement. “We appreciate the continued support of our many donors as we work to increase GNAO1 awareness and change lives.”

Conference participants from across North and South America will build relationships while reviewing existing GNAO1 medical papers and discussing ongoing research.  The conference will be streamed live on Facebook starting at 10:30 a.m. Click here to tune in.

The Bow Foundation is dedicated to supporting GNAO1 families through enhanced research and increased awareness. The foundation was launched in April of 2017 by two families who have children with a GNAO1 disorder. Visit www.BowFoundation.org to learn more or donate.

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Local Charity Funds UVA Rare Disease Research

James UVA Check

James Fox, a GNAO1 patient, drops off the Bow Foundation’s $50,000 check to UVA. 

August 9, 2017

Charlottesville, VA – The Bow Foundation today announced a grant of $50,000 to the University of Virginia School of Medicine to fund research into a rare genetic disorder with no common name.

The cutting-edge project will be led by Michael McConnell, PhD, and will study GNAO1 gene mutations. Roughly 50 children worldwide are impacted by a GNAO1 disorder. Children with the disease suffer from severe developmental delays, seizures, and movement disorders.

“We are honored and excited to be able support this great project at the University of Virginia,” Bow Foundation Co-Chairs Emily Bell and Alice Fox said in a statement. “Dr. McConnell’s research will help pave the way to a brighter future for children like ours who are impacted by a GNAO1 disorder. We look forward to gaining new insights and funding additional studies as we work to increase GNAO1 awareness and change lives.”

McConnell, of UVA’s Department of Biochemistry and Molecular Genetics, is a leader in precision medicine. His work is focused on unlocking the potential of stem cell therapy to deliver care for patients with genetic-based diseases. McConnell utilizes a technique that takes tiny skin samples and creates pluripotent stem cells (iPSCs), which in turn can be developed into neurons for further study. His research has the potential to increase understanding of genetic disorders and may ultimately lead to new or better treatments.

“I’m thrilled that we are able to team with the Bow Foundation to do this important work. Scientists using pluripotent stem cells have made a number of exciting new discoveries in neurological disorders over the past few years,” McConnell said. “GNAO1 patient advocacy has been essential to bringing cutting-edge science to this rare disorder.”

The Bow Foundation is dedicated to supporting GNAO1 families through enhanced research and increased awareness. The foundation was launched in April of 2017 by two families who have children with a GNAO1 disorder. Visit www.BowFoundation.org to learn more or donate.

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Mira – It’s All Good

This article was previously published on Mira’s family’s blog Mira Moves Mountains.  Here  her mom shares an update on Mira’s progress and how to focus on the positives of this difficult journey. 
Written by: Mira’s Mom Nikki

Our little family has an awful lot to be thankful for lately.   I’d love to share with you some of the many ways in which we continue to be surprised and delighted by the hidden joys of raising a child with a significant disability.  

The last couple of months have brought so many joyous opportunities, encounters, and gifts our way.  Through these, we are learning to slow down, focus on the present, and celebrate what each day brings.  Mira is progressing in more ways than we could have imagined, and we are beyond proud of how hard she works every day, always with a smile (and sometimes with borderline psychotic laughter).    

I may have touched on this before, but one of the most surprising and profound aspects of raising Mira so far has been our immediate and intense bonds with other special needs families.  Regardless of the child’s disability, special needs families innately understand one another and the struggles and triumphs that are part of the gig.  But when families whose children share the same extremely rare genetic condition get together…WHOA.  

Last month, we got to have another GNAO1 family over for dinner while they were in town from Arizona.  There are other GNAO1 families in the KC metro area, but we just haven’t had a chance to connect in person yet.  So we jumped at the opportunity to get to meet this family on their stop through our fair city, and let me tell ya…life changing.  (And sorry to the parents in question if you’re reading this and are totally disturbed by how much we’re fawning over you…but James already sent you the world’s sappiest message, so I think you have a rough understanding of our affection for you.)  Getting to see Mira and their daughter, age 4, in the same room playing together was intense and incredible.  Their daughter is doing tremendously well and we were so encouraged by her progress and the testimony of her parents regarding which therapies and tools were most successful for them (spoiler alert: Mira will start therapeutic horseback riding this fall or early next Spring!).  Their daughter is so gorgeous and sweet and funny that she makes Mira look like a freaking devil monster.  Seriously.  And if it wasn’t already enough to connect face to face with another family sharing our exact journey, we also genuinely liked these people!  A lot!  And really wish they didn’t live so far away so we could hang out with them!  AND…they are super generous!  They kindly sent us their daughter’s old UpSee which she had outgrown, so now Mira and I can practice walking without the $500 price tag.  They also lent us a special vest and bodysuit called a DMO (wearable orthotics, basically) to try out with Mira and see if they might be helpful to her.  This package of all packages also came with a rudimentary communication system to try, and a beautiful hand-written note…that was totally destroyed because the package arrived in a terrible rainstorm and we weren’t home so we have no idea what it said.  But we’re 99.9% sure it said “WE LOVE YOU.”  

And speaking of glorious gifts…can we talk about the new wheelchair???  OMG it’s so amazing!  Thank you, thank you, THANK YOU to all who lovingly donated to Mira so she could obtain this incredible piece of equipment.  It has already made our lives so much easier, and she has access to so much more than she ever has.  As a bonus, she seems to really enjoy being in it, and even requests it pretty often!  One of her favorite things to do is hold my hand while walking so I’m right beside her.  We crash into things…a lot…but she likes that, too.  Who would have thought we’d be so happy to have a wheelchair for our 21-month-old?  Life sure is crazy.  

Another weird and wonderful new addition is our handicap tags.  While we don’t have a lift van yet, finding room in a traditional parking space to pull up Mira’s big new chair on the side of the car to get her into it was really challenging.  I felt kind of guilty applying for a tag at first because the wheelchair is pretty much just a big, fancy stroller, but you know what?  Screw it.  It helps so much to have that extra bit of space and not worry about opening our doors too wide or scratching the vehicle next to us.  Also, I get really stressed out when people wait for a parking space, so being able to park in spaces that far fewer people are waiting for gives us the freedom to slow down and deal with her equipment properly, rather than rushing to get it all put away safely.  Also, it keeps me from cursing loudly and sweating profusely, and given how often I do those things anyway, it’s nice to get a break once in awhile.  

A more abstract gift is that of others’ devotion to GNAO1 research.  A member of our small GNAO1 community and her husband have established a nonprofit, The Bow Foundation (https://gnao1.org/), which “is dedicated to supporting GNAO1 families through enhanced research and increased awareness…working to fund cutting edge research to benefit those with GNAO1 disabilities and other similar rare diseases and neurological conditions.” Through their incredible perseverance and dedication, they have secured the opportunity for a scientific panel discussion about GNAO1 research at a national neurology conference in Washington, D.C., this November.  Additionally, researchers at Michigan State University are very close to determining better drug treatment options for GNAO1 patients based on whether they present with early infantile epileptiform encephalopathy (EIEE17) or Neurodevelopmental Disorder with Involuntary Movements, or NEDIM (what Mira has).  This is just too exciting to even begin to describe!  Go, science, go!!!

And this last little note isn’t so much a gift (but maybe it kinda is?) so much as an update, but we are now back to an umbrella diagnosis of Cerebral Palsy, attributable to a GNAO1 defect.  We’ve consulted with Mira’s pediatrician about it and he’s hopeful, as are we, that having CP as her primary diagnosis will open more doors to her for needed services and supports.  So you may hear us tell strangers she has CP if they ask, or you may hear us (me) continue to delve into a lengthy, unsolicited, and often emotional explanation of her specific genetic mutation.  Please just bear with us as we figure out the terminology we’re most comfortable with, and thank you for being on this roller coaster with us!

So now for the really fun part: Things Mira Does Now

*She eats better!  We are still almost positive she’ll be getting a feeding tube by the end of the summer as a safety precaution (don’t even get me started on my mixed emotions about this huge decision), but she will continue to eat and drink as much as possible orally.  Her team at school reports that she is making excellent progress with traditional feeding therapies, and we’ve definitely seen some big changes at home!  She is holding her bottle better, opening her hands and really working to bring it to her mouth.  She still can’t quite hold it independently, but she LOVES trying and receiving praise for her continued effort.  She’s also been taking more and more liquid out of a transition cup, moving away from using a baby bottle with a nipple.  The next step is straw training, and while we initially thought there was no way she could get there, we’re seeing more and more signs that she could very well be using a straw in the future!  And speaking of cups…good lord that girl loves cups.  I would say if there’s one thing she likes more than pretty much anything in the world, it’s getting to take sips of whatever we’re drinking (except booze) out of a “grownup” cup.  And she’s actually getting pretty dang good at it!  Now if we can just kick her coffee habit….  She’s also eating a lot more and doing well with slightly chunkier textures.  She loves seeing us blend up meals for her, and we love that she gets to eat what we’re eating, just in a different form.  

*She destroys things for fun.  Man does she love destroying things.  Knocking down towers of blocks, slamming around baby dolls, clearing her desk with a malicious swipe of her arm…I even have an e-mail from her occupational therapist saying, “She really does love to destroy stuff”.  I’m not making this up.  We’ve also been told in an official team meeting that “she has kind of a dark sense of humor”…and we dig that.  I mean she can’t ACTUALLY hurt anybody…right??

*She got her first word!  Mira now proudly, loudly, and CONSTANTLY says “more”.  It comes out like “muh”, but it’s said in the appropriate context and she’s very consistent with it.  Her team at school all hears it, too, so we know we’re not making it up!  The only problem with this, if it can even be called a problem, is that she says it when she actually wants more of something (like another bite), but also when she just wants something she sees.  Or for milk.  Or for mama.  So it’s AWESOME that she can communicate all of those needs to us verbally, but sometimes it’s a little tricky figuring out what she actually wants.  We’re getting better at it, though, and are just over the moon that this is even happening!  Blown away!!!

*She is developing a proper gait pattern!  We definitely still have a lot of work to do on this, but we’re very encouraged to see her pick up her legs in the correct pattern when practicing walking. She needs a bit of prompting (like holding one foot down to allow the other to come up), but everyone can tell that cognitively, she knows exactly what to do.  It’s just a matter of getting her legs to comply with her brain’s command.  It’s so cute to watch her take steps, too, because they’re very deliberate.  It’s truly the most charming thing you’ll ever see.  Sometimes her high/fluctuating muscle tone in her legs makes her pick them both up at the same time, but she’s getting faster and faster at putting them back down to regain her balance.  

*She stands up when she’s asked to!  This is so awesome to me.  The most proof we have (in my opinion) that big changes are taking place.  If Mira is seated and her feet can touch either the ground or a footrest (really anything sturdy), you simply have to ask for her hands (she gives them to you), then say, “Stand up!”…AND SHE STANDS UP.  Like, immediately. It’s bonkers.  I’m obsessed with it.  So is she.  🙂  

I’m sure there are many wonderful things I’m forgetting, but those are the highlights of the last few months for me, at least as they relate directly to Mira and our family’s journey with this unique disability.

I would say that the best (and most surreal thing) to happen lately, though, is that a German family somehow found our blog, and have utilized the connections we could facilitate for them to get help for their 15-year-old daughter who was diagnosed only a week ago.  

Her family has spent fifteen years having no idea what caused their daughter’s severe movements and other limitations.  Then they got the diagnosis, and were still at a loss as to next steps, as their girl was in the hospital due to a severe movement storm and was so sedated she could not move at all.  They are now aware that there are far more cases worldwide than they or their doctors initially realized, they have a broader network from which to gain treatment insight, and have been connected to neurologists who have performed successful DBS surgery on these patients.  Beyond that, they were immediately and lovingly accepted into our GNAO1 Facebook community and I hope they continue to stay connected and share in this journey with the rest of us.  

As I’ve said before, it often feels self-indulgent to blog about our experiences and share our daughter’s very personal and scary reality with a largely unknown audience, especially without her consent.  But this connection we made proved that it’s so, so worth it.  I hope that we can continue to share our experiences so that others who may encounter similar situations, or even the same rare diagnosis, can find a safe place to connect, share, learn, and receive support.  

You can read more about Mira and her family on their blog Mira Moves Mountains