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2023 Year In Review

Dear GRIN2B Families, Friends and Supporters,

2023 was a memorable year full of exciting milestones. We opened the first North American Center of Excellence for GRI-Related Disorders at the Children’s Hospital Colorado. After working hard for several years to develop this idea, it felt so good to see the clinic finally open last May and start seeing patients. We are proud to support this endeavor and hope we can eventually fund additional Centers across the United States.

The first commercial clinical trial for GRIN2B patients began enrolling patients in Europe. As we wait on FDA approval in the United States, we will continue to advise Grin Therapeutics on their clinical trial design.

Our Board of Directors worked hard to create our first 5 year Strategic Plan. This process included in depth surveys completed by our board and community, as well as several lengthy planning meetings where we evaluated our programs and initiatives and shared our goals for moving our organization forward. We are slowly but surely working through our tactical action plan to make our Strategic Plan a reality. 

Though we didn’t host an in-person conference ourselves in 2023, we were able to attend numerous conferences and meetups within the larger GRI community and Rare Disease spaces. Through these events, we were able to have fruitful conversations with families, researchers, clinicians and industry professionals. We are grateful for all the collaborations that come from attending these events. We really are stronger when we all work together on the individual pieces of the bigger picture.

And in the midst of everything, we also experienced devastating losses in our community. These tragedies remind us that there is still so much work to do for our community members in unraveling the mystery of GRIN2B. We simply don’t have the luxury of sitting back and hoping someone else will do something. Our community is too small. It’s up to each of us to make a difference and help our loved ones with GRIN2B. 

You don’t have to do it all. Just pick one thing to focus on if that’s all you can do. Join a patient registry. Fundraise. Participate in research. Watch a webinar. Attend our July Family Weekend in Colorado. Join a Meetup. 

Above all, we strongly encourage you to participate in research. An engaged community that contributes to research is our surest path forward to achieving successful clinical trials. Simply put, we need more data in order to move the needle.

Please take the time to read through all of our highlights from 2023 and our plans for this year. We are here to support each and every one of you and are happy to answer any questions. 

As always, we are committed to providing support and education to our GRIN2B families, promoting awareness of this ultra-rare disorder and funding research. Our vision is a world where every family impacted with a GRIN2B diagnosis feels empowered and supported.

With hope,

Liz Marfia-Ash, GRIN2B Foundation Board President


2023 Year In Review

Operational & Administrative 

  • Raised $203,508 in income.
  • Gathered data from two community surveys.
  • Developed our first Five Year Strategic Plan.
  • Developed a Corporate Sponsorship packet.
  • Began planning for 2024 Family Weekend Conference.

 

 

 

Support 

  • Private parent support group grew from 723 to 809 members, representing 52 countries.
  • 104 families completed our family registry on our website.

  • Continued our Bee Connected Meetups for families to connect and learn about resources.
  • Provided 7 Patient Assistance Grants.
  • Sent 3 Comfort Care Items to hospitalized patients.
  • Continued to support the GRIN2B family we rescued from Ukraine in 2022. 
  • Wrote a support letter for a family to help them obtain regional services.
  • Provided guidance to families re: signing up for registries and accessing the GRIN Portal.
  • Continued to develop our Welcome Booklet for new families. (coming soon!)
  • Developed Registry Info Sheet. 
  • Partnered with Mejo, a medical journal app specifically geared towards rare disease families. 
  • Created Amazon Gift Guide, with curated gifts for GRIN2B children. 

 

The financial support provided has been instrumental in alleviating the burden of expenses associated with our son’s DMI (Dynamic Movement Intervention) intensive therapy. The impact of these intensives on Jack’s overall development has been remarkable. Thank you once again for your unwavering support” 

– Dianna, GRIN2B Mom, Patient Assistance Grant Recipient

 

Awareness 

  • 21 teams from 8 countries participated in our 4th Annual Bee Active for GRIN2B Walk, Run & Roll, raising $62k.
  • March Awareness Week campaign: profiled 18 patients, shared 2 symptoms videos and shared graphics with facts & resources.
  • Created a new Awareness Video during March.
  • Created a downloadable Awareness card for families.
  • 2700+ followers on our public Facebook page
  • Produced 1 new episode of Celebrating Rare: The GRIN2B Podcast.
  • Created and sold our 2024 GRIN2B Calendar.
  • Continued fundraising partnerships with Billy Footwear and See’s Candies. 
  • In lieu of Amazon Smile shutting down, we joined the Walmart Round Up program.

 

“This past May we visited the Center of Excellence at Children’s Hospital in Aurora. It was so nice to be able to walk into a place and not have to explain what genetic disorder our daughter had, they just knew everything, plus more! We walked away with more understanding and a sense of belonging to a whole community.” 

– Jelena, GRIN2B Mom

Research & Medical 

  • GRI Center of Excellence at Children’s Hospital Colorado began seeing patients in May.
  • Awarded $20k in research funding in partnership with Uplifting Athletes to Riley Perszyk at Emory University.
  • Hosted webinars on the Center of Excellence and Gain & Loss of Function Variants.
  • Shared research opportunities with community – Inchstones Project, GRI Faces Project, Combined Brain Biomarker project, Project Wellcast.
  • 3 blood samples from GRIN2B patients were added to our biorepository through Combined Brain.
  • Participated in ​​Simons Searchlight’s “Shine your Searchlight” campaign to encourage families to join their GRIN2B registry.
  • Added Dr. Scott Metrick, GRIN2B parent and retired Neurologist to our Medical Advisory Board.
  • Sponsored and spoke at Cure GRI Conference in Boston.
  • Sponsored and spoke at iGlur (Glutamate Receptor) Conference in Chicago.
  • Attended the National Organization for Rare Disorders Breakthrough Summit.
  • Joined Cure GRIN Foundation’s Research Grant Review Committee to determine future projects to fund.
  • Supported Cure GRIN’s application to the CDC for an ICD-10 code for GRI Disorders.
  • Continued to work with GRIN Therapeutics on outreach and feedback on their Honeycomb clinical trial.
  • Continued to work with Duke University on the next phase of their Orca Study.

GRIN2B Foundation has been able to support over $365,000 in GRIN2B research to date – and this amount is growing exponentially. Learn more about our funded research projects here – http://grin2b.com/awarded-grants/

If you are interested in learning more about the research process, we recommend you download the following toolkit from our partner, Global Genes – Rare Research Roadmap.

On the horizon for 2024

  • Host our 2024 GRIN2B Family Weekend July 19-21 in Denver, Colorado.
  • Coordinate first Research Roundtable to develop our Strategic Research Priorities (July 19th, 2024).
  • Investigate new hospitals to partner with for GRI Center of Excellence sites.
  • Expand our Board of Directors, and develop a plan to hire our first staff member.
  • Celebrate GRIN2B Awareness Week, March 12-18. This year’s theme is “Bee Aware & Take Action.”
  • Re-open our Patient Assistance Grant Program in March.
  • Announce our next Research Grant award.
  • Continue to work with Duke University on Phase 2 of their Orca (communications) Study.
  • Work through our tactical action items from our Strategic Plan.
  • Develop a Volunteer packet.
  • Finalize our Welcome Booklet for New Families and translate into several languages.
  • Host more Bee Connected Meetups & informational webinars.
  • Host 5th Bee Active for GRIN2B Walk, Run & Roll Fundraiser in September 2024.
  • Continue to Collaborate with GRIN Therapeutics on the study design for their Honeycomb Trial.
  • Begin to engage with the FDA.
  • Continue to collaborate with GRIN clinicians, researchers and partner advocacy organizations.

Get Involved in 2024!

  • Join a Committee.
  • Attend our 2024 GRIN2B Family Weekend in Denver this July. Registration info coming soon.
  • Make a donation
  • Become a Corporate Sponsor. Email fundraising@grin2b.com.
  • Fundraise for us! So many people ask us about funding more research or additional Centers of Excellence, but we cannot do this without increased fundraising from our community.
  • Follow us on Facebook and Instagram.
  • Join our Family Registry.
  • Participate in research studies that are appropriate for your child/family.
  • Keep a look out for announcements about upcoming webinars and meetups!

 

General inquiries & Conference Planning – liz.marfia-ash@grin2b.com

Center of Excellence – donna.dunn@grin2b.com

Family Support / Patient Grants – brittaney.crider@grin2b.com

Fundraising – fundraising@grin2b.com

 

Thank you!

We are grateful for the following organizations and families that donated $2500 or more in 2023.

Ila Goldstein
Dave Matthews
Beth and Oliver Wright

 

2022 Year In Review

Dear GRIN2B Families, Friends and Supporters,

GRIN2B Foundation Board of Directors

2022 was our biggest year yet! We were thrilled to connect in person at our July GRIN2B Family Weekend in Chicago and at our Bee Active fundraising events. We started laying groundwork for clinical trial readiness through the development of our Center Of Excellence, our partnership with Duke University on their Orca Communication Measure and, most excitedly, through our work with GRIN Therapeutics on the development of their Radiprodil clinical trial – the first commercial trial for GRIN2B patients. 2022 also saw us supporting families in familiar and unexpected ways. We supported and rescued a family from Ukraine, wrote letters of support for families in need of local services and we offered up an ongoing way for parents to connect through our Facebook group and our Bee Connected Zoom Meetups. 

For research, we continued our partnership with Dr. Stephen Traynelis, awarding his lab $25K to continue their translational work with GRIN2B variants and animal models that are directed toward assessing potential therapeutic strategies. We nominated Dr. Riley Perszyk from Emory University to receive a grant through the Uplifting Athletes program and were thrilled when Dr. Persyk was chosen. We are also working with our sister organization, Cure GRIN Foundation, to assess potential future research projects to co-fund.

Our mission is intentionally broad to meet the diverse needs of our community. After 5 years, we are incredibly proud of our growth, but regret that we are limited in the amount of projects we can take on and research we can fund. Sometimes, we have to say no to projects due to limitations of funding, time and manpower. Rest assured that all our choices and programs are deliberate based on feedback and survey results from our community.

We are committed, as always, to providing support and education to our GRIN2B families, promoting awareness of this ultra-rare disorder and continuing to fund research. 

If you are interested in helping our mission, we encourage you to get involved. Consider joining a committee, or let us know if you have a specific skill set and are willing to volunteer your time. But most importantly, just stay connected in whatever way works best for you – read our emails, follow us on social media and/or join our meetups and webinars.

Our passionate Board of Directors has historically driven the bulk of the fundraising for our organization. While our team remains dedicated to the cause, there is no question that in order to expand our research objectives, we desperately need more families to help drive fundraising. We cannot continue to make an impact without more support.

If supporting research and creating additional Centers of Excellence is important to you, please consider helping us fundraise. We’re happy to brainstorm with you – just reach out to fundraising@grin2b.com.

Please read our list of 2022 accomplishments below and let us know if you have any questions. We look forward to a bright and busy 2023!

With hope,

Liz Marfia-Ash, GRIN2B Foundation Board President


2022 Year In Review

Operational & Administrative

 

 

 

 

 

 

 

 

Support

  • Hosted GRIN2B Family Weekend in July with 25 GRIN2B families and 100+ attendees.
  • Launched Bee Connected Meetups for families to connect and learn about resources.
  • Private parent support group grew from 646 to 723 members, representing 50 countries.
  • 103 families completed our family registry on our website.
  • Coordinated resources and helped rescue a GRIN2B family out of Ukraine.
  • Provided 4 Travel Stipends for families attending our GRIN2B Family Weekend.
  • Provided 2 Patient Assistance Grants.
  • Sent 1 Comfort Care Item to a hospitalized child.
  • Wrote support letters for 2 families to help them obtain regional services.
  • Provided guidance to families re: signing up for registries and accessing the GRIN Portal.
  • Family Advisory Committee began working on a Welcome Booklet for new families.

 

“Our son Alex is 15 and has refractory epilepsy that is resistant to treatment. We decided to seek help from the Neurology team at BC Children’s Hospital in Vancouver. We applied for a Patient Assistance Grant to help us with the costs associated with traveling. We have been so grateful for all the support and guidance we have received from the GRIN2B Foundation.” – The Caleb Family

“I am sincerely grateful to all of you for your help and support. Thanks to GRIN2B Foundation and everyone who cares, we are alive and well. In a difficult period when Russia came to kill and torture in our home, GRIN2B Foundation came to our rescue. The whole family was rescued and supported, evacuated to a safe place. With the financial support, we were able to buy food and medicine and survive a difficult period in Poland.” – Nadezhda Bilous, Ukrainian GRIN2B Mom 

 

Awareness 

  • 19 teams from 3 countries participated in our 3rd Annual Bee Active for GRIN2B Walk, Run & Roll, raising $46k.
  • March Awareness Week campaign: profiled 22 patients, shared 2 symptoms videos and shared graphics with facts & resources.
  • Created a new Awareness Video during March.
  • 2300+ followers on our public Facebook page
  • GRIN Therapeutics produced a series of videos featuring our community during the GRIN2B Family Weekend. 
  • Created and sold our 2023 GRIN2B Calendar.
  • Started fundraising partnerships with Billy Footwear and See’s Candies. 

Research & Medical

  • Signed contract with Children’s Hospital Colorado to develop the 1st North American Center of Excellence for GRI-gene Disorders.
  • Awarded $25k to the Stephen Traynelis Lab at Emory University to advance their translational work with GRIN2B variants and animal models that are directed toward assessing potential therapeutic strategies.

    The Team from GRIN Therapeutics
  • 4 stem cell lines for GRIN2B patients generated for research through partnership with Simons Searchlight.
  • Collected 5 blood samples from GRIN2B patients for our biorepository through Combined Brain.
  • Dr. Caitlin Hudac continued her EEG BioGene study, seeing patients at the GRIN2B Family Weekend.
  • Visited and gave feedback on GRIN Therapeutic’s first U.S. clinical trial site.
  • Continued to work with GRIN Therapeutics on outreach and feedback on their upcoming Radiprodil clinical trial, including drafting a letter of support for the FDA.
  • Helped identify and recruit families for Duke University’s Orca Study.
  • Presented to Duke University about GRIN2B.

 

A note about research. Sometimes people ask us why we aren’t further along in treating GRIN2B. Why aren’t we supporting either more research or specific types of research?

The fact is, it takes a LOT of money, time, understanding, safety and efficacy. It also takes a lot of bio specimens, patient participation and clinical trials. It takes a lot of collaboration with our Medical Advisory Board. While we believe Parents are important for driving research, it is still critical to rely on experts for guidance. And the truth is that wanting to fund more research simply isn’t enough. The members of our Medical Advisory Board have a diverse background and many of them are considered to be the foremost experts on GRIN disorders and NMDA receptors. 

We would fund dozens of research projects a year if our budget allowed for it. Most scientific research is funded through a combination of government grants, companies doing research development and non-profit foundations. In rare diseases it takes a lot of time to find and apply for these opportunities, as well as a lot of research and expertise to get the ball moving. We pride ourselves on our ability to make our funding choices very thoughtfully and carefully. 

GRIN2B Foundation has been able to support over $245,000 in GRIN2B research to date – and this amount is growing exponentially. Learn more about our funded research projects here – http://grin2b.com/awarded-grants/

If you are interested in learning more about the research process, we recommend you download the following toolkit from our partner, Global Genes – Rare Research Roadmap.


On the horizon for 2023

  • Finally launch Center of Excellence for GRI Disorders in Colorado, May 2023.
  • Review results of our latest Community Pulse Survey.
  • Celebrate GRIN2B Awareness Week, March 12-18.
  • Sponsor and attend Cure GRIN conference in March.
  • Develop our 1st Strategic Plan.
  • Develop Corporate Sponsorship packet.
  • Partner with Uplifting Athletes to co-fund a Young Investigator Grant for Dr. Riley Perszyk at Emory University.
  • Finalize our Welcome Booklet for New Families and translate into several languages.
  • Continue our Bee Connected Meetups.
  • Plan various informational webinars.
  • Begin early planning for the 2024 GRIN2B Family Weekend.
  • Host 4th Bee Active for GRIN2B Walk, Run & Roll Fundraiser in September 2023.
  • Continue to collaborate with GRIN medical community and partner organizations on future research projects to fund.
  • Continue to recruit new volunteers, board members and advisors.

Get Involved!

General inquiries – liz.marfia-ash@grin2b.com

Center of Excellence – donna.dunn@grin2b.com

Family Support / Patient Grants – brittaney.crider@grin2b.com

Family Advisory Committee – lauren.hookings@grin2b.com

Fundraising – fundraising@grin2b.com

 

GRIN2B Foundation Awards $25K to Emory University

GRIN2B Foundation is pleased to announce an award of $25,000 to Dr. Stephen Traynelis’s Lab at Emory University for a project entitled:

“The Impact of NMDA Receptor Potentiation on Synaptic Plasticity in GRIN2B LOF Variants”

Dr. Traynelis is a Professor of Pharmacology and Chemical Biology at the Emory University School of Medicine in Atlanta, GA, and the Director of the Center for Functional Evaluation of Rare Variants (CFERV). For this project, the lab will test whether administration of an allosteric potentiator of NMDA receptors can rectify deficient synaptic plasticity observed in mice harboring a LOF GRIN2B variant.

“We are delighted to have received additional financial support from the GRIN2B foundation for our work on GRIN2B variants identified in patients. Our past funding has allowed us to translate in vitro functional results with GRIN2B variants into animal models, which we have developed, characterized, and are using to assess potential treatments. This latest round of funding will allow us to significantly expand our efforts on translational work with GRIN2B variants and animal models that are directed toward assessing potential therapeutic strategies. Specifically, these funds will accelerate our current work assessing how NMDA receptor potentiation (through glycine site agonists or positive allosteric positive modulators) can restore deficits in cellular models of learning observed in mice harboring a GRIN2B variant that reduces in vitro models of plasticity. We are excited to complete these experiments, and look forward to working to move our research results on a translational path toward establishing new therapeutic strategies.” – Dr. Stephen Traynelis

Hear Dr. Traynelis and Board President, Liz Marfia-Ash speak about this project on our Giving Tuesday Facebook Live around the 20:15 mark.

Read about our previously funded projects here.

We would not be able to continue funding GRIN2B research without our community of patients, families, scientists, clinicians and people like you. Thank you for believing in and powering our mission. Make a donation today and impact vital research as we drive closer to treatments every single day.

Our team is always working to identify additional research projects to fund. Stay tuned for our next research funding announcement in mid January.  

DONATE TODAY TO CONTINUE SUPPORTING RESEARCH

Thank you,

Liz Marfia-Ash, GRIN2B Foundation Board President

So Your Child Received a GRIN2B Diagnosis; What’s Next?

By Liz Marfia-Ash, President and Founder of GRIN2B Foundation

In our Private GRIN2B Parent Support Group on Facebook, a parent recently commented that most GRIN2B Parents have read the blog post I wrote back in 2016 – To the Person Who Just Googled GRIN2B For the First Time. I don’t know if that’s true, but, regardless, it’s an immense responsibility and privilege to know that my words are impacting newly diagnosed families. It’s why I wrote the article in the first place, but it’s quite another thing to hear someone else say it.

In 2016, I wrote to give future families hope. 

I wanted more families to find us and know that we were getting organized. I wanted families to have what I didn’t have – a soft place to land when they received the diagnosis for their child. We’ve accomplished that, and families from all over the world have found us. 

Now I’m writing to tell you what to do next. A lot is happening in our community in the coming year, and I want you to be prepared and know how you can participate.

Two of the events we’re most excited for in 2022 are hosting our twice-postponed GRIN2B Family Weekend in July 2022 and launching the first ever Center of Excellence for GRI Disorders! 

The Family Weekend will be July 15th and 16th, 2022 at the Hyatt Regency O’Hare, just minutes away from O’Hare Airport in Chicago. We’re planning an amazing two days for families, full of GRIN2B updates, resources and as many opportunities for families to connect and bond as we can squeeze in. 

The Center of Excellence is an idea we have been working on since late 2019. Working with input from the team at Cure GRIN Foundation, this Center will be a place where all patients with GRIN, GRIA, GRIK and GRID Disorders can go to see a Team of experts. We are still finalizing the details, but the first Center will hopefully open in Spring of 2022 in Denver, Colorado. Our dream is to open more Centers around the U.S. in future years, though that will be dependent on increasing our fundraising. More to come soon!

Excitingly, we are also finally on the precipice of our first clinical trial! In case you missed the news, the newly formed GRIN Therapeutics is launching a clinical trial for the drug Radiprodil in 2022 for GRIN2B patients with a Gain of Function variation. If you’re not sure what Gain of Function even means, you can get a simple definition at the bottom of this page. Or read this blog from Dr. Tim Benke.

Or, follow along for my quick and dirty explanation.

  1. Your child receives their diagnosis. Their genetic report will list the details of your child’s specific variant. (Example: c.1146 G>A) This page helps explain the different types of variations that can occur and how to read your child’s genetic report.
  2. Each variant is then going to be further classified as either Gain of Function or Loss of Function. 
  3. Different medications will be recommended depending on which type of classification your child falls into (Gain or Loss). 
  4. As previously mentioned, the upcoming Radiprodil clinical trial is only for Gain of Function patients. There will be additional trials down the line for Loss of Function patients.

We are working with the team at GRIN Therapeutics to help design this upcoming Clinical Trial and determine the best locations to have trial sites. But to do this, we need to know which patients are classified as Gain of Function. And for that to happen, we need every GRIN2B patient to be enrolled in the GRIN Variant Patient Registry.

So, if you haven’t already, please do the following:

  1. Enroll in the Registry
  2. Once enrolled, your child’s variant info will be sent to the Center for Functional Evaluation of Rare Variants (CFERV) at Emory University where they will perform the functional analysis to determine if the variant is Gain or Loss.
  3. If the variant is found to be Gain of Function, start thinking about the possibility of enrolling your child in the upcoming clinical trial.

Feeling overwhelmed yet? It’s complicated for me to explain, so I imagine how this must feel to newly diagnosed families. Our Family Advisory Committee is currently working on developing Welcome Packets and Checklists for our Community to help get you started on the right foot. In the meantime, I’ve created some helpful checklists below. Keep in mind, these lists are not all inclusive. Think of this post as merely a starting point, and know that something more comprehensive is in the works.

Please, please, pretty please put these at the top of your list (if you haven’t already done them).

  • JOIN the Family Contact Registry for GRIN2B Foundation. This puts you on our organization’s mailing list. It also gives us a general idea of how many families we are supporting and where everyone is located.
  • ENROLL in the GRIN Variant Registry (See all the reasons I mentioned above.)
  • JOIN our private GRIN2B Parent Support Group (if on Facebook) to connect with other families – we’ve got an incredibly welcoming community! (Be sure to answer our questions when you request to join or we cannot approve you.)
  • FOLLOW us on Facebook, Instagram, Twitter and YouTube

Other things to keep on your radar and do when you can, if you can.

  • Start educating yourself on the clinical trial process. Read this blog and watch these webinars.
  • Save the Date for our Family Weekend July 2021. (We will have Travel Stipends available and registration will open early 2022.)
  • Enroll in Simons Searchlight’s GRIN2B study.
  • There are more research studies in the pipeline. Keep an ear out for new opportunities.
  • Fundraise for us, or consider making a monthly or one time donation. We see our GRIN2B families as families first and foremost and NOT as donors. That being said, GRIN2B is not really the type of disorder that is going to get donations from random, rich strangers. Our biggest donors are either families themselves or friends and relatives of GRIN2B patients. We have a lot going on in the coming years, and we are going to need the community to participate in fundraising. You don’t need to throw a fancy gala. We have so many easy ways to fundraise for us listed on our website. The truth is, we cannot keep working at this current pace without more fundraising support.
  • Let us know if you want to get more involved. We’re always looking for people skilled in the following areas – Fundraising, Legal, Financial, Marketing, Science/Medical. Email me at liz.marfia-ash@grin2b.com.

Resources to help you and your extended family. (The holidays are a great time to share these resources with loved ones who may be interacting with your family.)

Recommended blog posts. (They’re short and easy to digest and should feel relatable.)

If the above lists have you feeling stressed out, take a deep breath. And then sit and think for a second about how none of these programs, clinical trials, future centers of excellence, resources, fundraisers and support groups existed seven years ago. We have so much to be thankful for. “I don’t have to chase extraordinary moments to find happiness – it’s right in front of me if I’m paying attention and practicing gratitude.” – Brene Brown

Ashley Reid, a GRIN2B mom on our Family Advisory Committee recently shared an amazing testimonial about our organization.

“Whether we are looking for community, advice, the latest research studies or just to feel less alone, the GRIN2B Foundation makes room for everyone.”

BEE ICONMaking room for everyone is at the heart of our Foundation. Everyone comes to us at a different place; some have babies who are being diagnosed, and some are finally putting a name to what their adult children have lived with their entire lives. There is no right or wrong way to process the diagnosis or get involved with our community. But, for those who are ready to get involved in whatever way possible, this blog is the resource you are looking for.

There’s truly no rush to do everything at once. Just do the next right thing.

GRIN2B Foundation Awards $40K Research Grant to Emory University

GRIN2B Foundation is pleased to announce an award of $40,000 to Emory University to promote scientific understanding of the ultra-rare genetic condition known as GRIN2B-Related Neurodevelopmental Disorder.

GRIN2B Foundation’s 2021 research grant recipient is Dr. Hongjie Yuan, Assistant Professor of Pharmacology and Chemical Biology at the Emory University School of Medicine in Atlanta, GA, and Deputy Director of the Center for Functional Evaluation of Rare Variants (CFERV) for his research project entitled:

“Functional Evaluation and Therapeutic Strategies for an Animal Model Harboring a Disease-associated Gain of Function GRIN2B Variant”

Building on the grant Dr. Yuan received a year ago to study the impact of a Loss of Function GRIN2B variant on NMDA receptor function, Dr. Yuan and his team will now replicate the study, only this time with a Gain of Function GRIN2B variant. ​​Using multiple techniques, they will show how a Gain of Function GRIN2B-p.Ser810Arg variant identified in a pediatric patient with intellectual disability and seizures influences synaptic activity/connectivity, seizure threshold and behaviors in a knock-in mouse line harboring the variant. They will also assess if the addition of substances (e.g. Radiprodil, Memantine, Ketamine) to the mouse models will lessen the impact of the GRIN2B variant. 

Read more about Dr. Yuan, his current project and our previously funded projects here.

According to Dr. Stephen Traynelis, Professor of Pharmacology at Emory University and member of GRIN2B Foundation’s Medical Advisory Board:

“The GRIN2B Foundation has a history of funding cutting edge research on new treatment options for patients with GRIN variants. Dr. Hongjie Yuan is a leader in conceptualizing new therapeutic strategies for patients with GRIN variants. The ongoing work is exciting, has stimulated interest in the private sector for treatment strategies, and is poised to provide new insight into how the GRIN2B gene can influence development and human behavior. It’s hard to overstate the impact of this particular study for the community of patients and families associated with GRIN variants, enabled both by generous donations and the support of GRIN2B foundation.”   

We would not be able to award these important research grants without our community of patients, families, scientists, clinicians and people like you. Thank you for believing in and powering our mission. Make a donation today and impact vital research as we drive closer to treatments every single day.

DONATE TODAY TO CONTINUE SUPPORTING RESEARCH

Thank you,

Liz Marfia-Ash, GRIN2B Foundation Board President

 

Introducing GRIN Therapeutics

Dear GRIN2B Community,

We are excited to share that we finally have our first clinical trial on the horizon! We first met Dr. Muglia in 2019 at the GRIN Variant Conference hosted by CFERV in Atlanta. We’ve kept in touch with him and, in early 2020, he shared his interest in starting up a clinical trial for the drug Radiprodil, which he believes will be effective for GRIN2B patients with a gain of function variant. Please read the statement below from Dr. Muglia about his recently formed biotech, GRIN Therapeutics. We are working closely with the GRIN Therapeutics team to make this trial effective, and we will share more news in the coming months. This is an important first step towards effectively treating GRIN2B patients. We look forward to learning the ins and outs of the clinical trial process and educating our community members as well.

With hope,

Liz Marfia-Ash, GRIN2B Foundation Board President

Watch Dr. Muglia’s presentation at the recent GRIN Virtual Conference.


Statement from GRIN Therapeutics:

 On behalf of GRIN Therapeutics and Dr. Pierandrea Muglia, we would like to thank the GRIN community for inviting us to present at the 2021 GRIN Virtual Conference, where Dr. Muglia spoke about the recently formed biotech, GRIN Therapeutics. The company will be primarily focused on developing Radiprodil for children with gain of function genetic variants in GRIN2B.

I would also like to introduce myself: I am the Head of Community Engagement and Communications. I have also spent the last decade as rare disease advocate and the mother of a medically complex child. I joined GRIN Therapeutics to help facilitate the collaborative work with the GRIN community that is required to develop a potential treatment in an ultra-rare disorder. I took on this role so enthusiastically because your community is at the center of the story how this company was formed.

We look forward to sharing the next steps on this path with all of you.

-Hillary Savoie, Head of Community Engagement and Communications

Statement to the GRIN Community on GRIN Therapeutics and Radiprodil

The establishment of GRIN Therapeutics this month is not only the result of two years of work by our CEO, Dr. Pierandrea Muglia. It is also the result of the tremendous efforts of the GRIN community: The idea of this company was inspired by meeting the GRIN community two years ago at the 2019 CFERV Conference on GRIN Variants held at Emory University, in Atlanta.

Dr. Muglia came to this conference knowing that Radiprodil had a mechanism that suggested it might help patients with gain of function genetic variants in GRIN2B. What he didn’t expect was the maturity all the work produced by the GRIN community—from clinicians, researchers, advocates, and families working together.

This community inspired him to form GRIN Therapeutics to focus entirely on developing potential treatments for the GRIN community—beginning with Radiprodil. This passion has fed and inspired our small, patient-focused team, who we look forward to introducing to you in the coming weeks. Earlier this month, at the 2021 GRIN Virtual Conference, we announced our plans to initiate the first clinical study on Radiprodil in children living with GRIN2B gain of function, with a goal to establish appropriate dosing based on safety and initial effect.

We also shared the following details. Radiprodil:

  • Is a pediatric phase 2 ready, selective NR2B negative allosteric modulator
  • Has safety database from more than 400 adults
  • Was used safely in three treated infants with an effect on seizures/spasms in these treatment-resistant patients
  • Rectifies in-vitro overactive –NR2B gain of function of specific variants (N615I; V618G)
  • Shows anticonvulsant activity in several preclinical seizure models
  • Has potential to treat seizures and other symptoms in children with GRIN2B gain of function variants

In the next six to nine months we will develop a pediatric formulation and complete a submission to regulatory bodies. Most importantly, we will also engage in dialogue with key leaders from the GRIN community. The path to clinical trials is complex, however, we see you as our most important partners in the process to get to the first clinical trial in the GRIN2B.

 

GRIN2B Foundation is Part of COMBINEDBrain

In late 2019, GRIN2B Foundation became a founding member of COMBINEDbrain, a non-profit consortium of 25 patient-advocacy groups, each representing a different rare genetic neurodevelopmental disorder. COMBINEDBrain’s mission is to speed clinical trial readiness for severe cognitive disorders by pooling resources and working together across all of our member disorders.   

We have been both thrilled and honored to participate in CombinedBrain. Working alongside so many other like-minded organizations, all focused on treating and curing ultra-rare neurodevelopmental disorders has been truly empowering. In the past year, we have come to realize that though our disorders have different names and affect different genes, we have so many overlapping characteristics. As a group, we are able to share ideas, resources and contacts. We learn from and inspire each other and work together to find strategic partnerships. Most importantly, our membership in CombinedBrain helps spread much-needed awareness about GRIN2B-Related Neurodevelopmental Disorder and GRIN Disorders and gives us access to companies that can help us achieve our goal of finding targeted treatments for individuals with GRIN2B.

COMBINEDBrain was founded by Dr. Terry Jo Bichell, whose adult son has Angelman Syndrome. In 2009, Terry Jo went back to school, earning her PhD in neuroscience in order to work towards finding a cure. She created COMBINEDBrain in 2019 to share her experience with the next wave of rare diseases. She’s a force to be reckoned with in the rare disease community, and we are so grateful to have her as a mentor and friend.

The other members of CB that we are in collaboration with (in reverse alphabetical order) are:

Yellow Brick Road Project (HNRNPH2) is represented by Trish Flanagan, President. The YBRP connects families and drives research forward into HNRNPH2 mutations to improve these rare patients’ lives. This is a small but fiesty organization who are laser focused on getting to clinical trials, treatments and a cure for the rare X-linked HNRNPH2 related neruro-developmental disorder.

Schinzel-Giedion Syndrome Foundation (SGS) is represented by Nuala Summerfield, Founder and Chair. The organization’s mission is to provide support to families caring for a child with SGS, to raise awareness of SGS and to facilitate and support medical research that will help find better treatments to improve the quality and length of life of children living with SGS. The Schinzel-Giedion Syndrome Foundation is the only patient organisation for SGS and represents the international SGS community. 

SynGAP Research Fund (SRF) is represented by Mike Graglia, Managing Director & co-founder. SRF’s mission is to support the research and development of treatments, therapies and support systems for SynGAP1 patients worldwide. SRF is entirely parent led and has committed over $1.2M to research since it was created, 100% of donations go directly to support research. 

STXBP1 Foundation is represented by Charlene Son Rigby, President. The STXBP1 Foundation’s mission is to raise awareness of STXBP1 disorders, and to accelerate the development of therapies and hopefully a cure for our patients.

SLC6A1 Connect is represented by Amber Freed, CEO & Co-Founder. The mission of SLC6A1 Connect is to cure every person with SLC6A1.

SETBP1 Society is represented by Haley Oyler, President. Their mission is to provide support to individuals with SETBP1 disorder and their families, to promote discussion and fund research, and to bring awareness and education to the public. SETBP1 Society is an internationally-focused volunteer 501(c)(3) organization based in the US with a focus to identify targeted treatments to help individuals impacted by SETBP1 disorder.

SATB2 Gene Foundation is represented by Allison Kaczenski, President & Founder. The SATB2 Gene Foundation was established to enrich the lives of individuals with SATB2-associated syndrome, including those diagnosed with the condition and their families, through support, research and education. 

Project 8p Foundation is led by Bina Maniar Shah, President & Founder. Project 8p Foundation is a 501(c)(3) non profit organization established to accelerate the discovery of treatments for chromosome 8p disorders with a translational research program and a standard of care to empower meaningful lives in a unified community today. Chromosome 8p is not just a rare genetic disease, but the many genes and pathways can be clues to common brain-related diseases.

Project Alive  is represented by Kim Stephens, DBA, President. Their mission is to find and fund a cure for Hunter Syndrome (also known as Mucopolysaccharidosis or MPS II) through research and advocacy.Project Alive is a powerful voice for children and adults with Hunter Syndrome, bringing together families and advocates with researchers, industry, and regulators. 

PBD Project  is represented by  Andrew Longenecker, Founder. Their mission is to PBD Project is to fund medical research with the objective to provide meaningful positive clinical impact for patients with Peroxisome Biogenesis Disorders (PBD), with a focus on Zellweger Spectrum Disorder (ZSD) caused by mutations to PEX10 gene. 

NR2F1 Foundation is represented by Carlie Monnier, Board President. The mission of the NR2F1 Foundation is to empower families and individuals living with rare NR2F1 mutations through education, awareness and research. As a result of joining forces with other foundations, we aim to be leaders in patient empowerment and patient-led research for the rare disease community at large ultimately serving as a model to other organizations.

Malan Syndrome Foundation is represented by Dr. Christal Delagrammatikas. The mission of the Malan Syndrome Foundation is to improve the lives of individuals and families affected by Malan syndrome in the global community through support, outreach and research. The Malan Syndrome Foundation is a volunteer, parent-led organization. 

KIF1A.ORG is represented by Kathryn Atchely, President. KIF1A.ORG is a global community dedicated to improving the lives of those affected by KIF1A Associated Neurological Disorder and accelerating research to find a cure. Our relentless community of families, researchers, clinicians, innovators and supporters are determined to bring treatment to this generation of people affected by KAND.

GRIN2B Foundation is represented by Liz Marfia Ash, President & Founder. GRIN2B Foundation is a parent-run organization dedicated to furthering research on the GRIN2B gene and providing support and education to the small, but growing community of individuals and families impacted by a GRIN2B diagnosis. Though GRIN2B Foundation was the first GRIN2B-related organization formed, we are very proud to work in collaboration with many other GRIN2B and GRIN Disorder organizations that have since formed worldwide.  

Glut1 Deficiency Foundation is represented by Glenna Steele, Executive Director. The Glut1 Deficiency Foundation is a nonprofit patient advocacy organization dedicated to improving lives in the Glut1 Deficiency community through its mission of increased awareness, improved education, advocacy for patients and families, and support and funding for research. We are working hard to bring help and hope to the Glut1 Deficiency community. 

FOXG1 Research Foundation is represented by Nasha Fitter, CEO, Head of Research. The mission of the FOXG1 Research Foundation to accelerate research to find a cure for FOXG1 syndrome. We are dedicated to funding the world’s leading scientists that are integral along the Path to a Cure for all children with FOXG1 syndrome. We will continue to apply our research to solve related brain disorders. 

Foundation for USP7 Related Diseases is represented by Bo Bigelow, Chairman/Co-Founder. Their mission is to cure Hao-Fountain Syndrome (previously known as USP7-related diseases). We do this by funding research and identifying more patients. In funding research, we seek to (1) uncover methods of activating USP7 to rescue this haploinsufficient phenotype; and (2) understand how alterations in proper functioning of endosomal protein recycling cause seizures and other neurological problems. 

FamilieSCN2A Foundation is represented by Leah Schust Myers, Executive Director. Their vision is to find effective treatments and a cure for SCN2A related disorders. Their mission is to improve the lives of those affected by SCN2A related disorders through research, public awareness, family support and patient advocacy. FamilieSCN2A Foundation was created by parents of children suffering from SCN2A related disorders who work unwaveringly to support both families and research.

CureGPX4 is represented by Sanath Kumar Ramesh, Founder. The organization’s mission is to create treatments to Spondylometaphyseal Dysplasia Sedaghatian type (SSMD). 

CureSHANK  is represented by  Geraldine Bliss,  Founder and President. Their mission is to accelerate the development of treatments for Phelan-McDermid Syndrome and SHANK-related disorders.  Their approach is to identify and fund projects that overcome critical barriers to successful drug development and to coordinate scientific efforts to improve efficiency and speed in the field.  

CureGRIN is represented by Keith McArthur ,CEO and Head of Science. Their mission is to improve the lives of people living with GRIN Disorder. The foundation is founded and run by parents that are committed to improve the lives of people with GRIN disorder.  

CHAMP1 Research Foundation  is represented by Jeff D’Angelo, Founder, Research Committee Chair. Their mission is to improve the lives of those affected by CHAMP1 through clinical research, effective treatments, public awareness, early detection, family support and patient advocacy. 

CACNA1A Foundation is represented by Lisa Manaster, President. Their mission is to increase awareness of CACNA1A variants, support  individuals and families affected by CACNA1A, and raise funds to support research and treatment options to find a cure for CACNA1A.  

 

GRIN2B Foundation Awards $45K Research Grant to Emory University

GRIN2B Foundation is pleased to announce an award of $45,000 to Emory University in its 2020 research grant initiative to promote scientific understanding of the ultra-rare genetic condition known as GRIN2B-Related Neurodevelopmental Disorder.

The recipient of GRIN2B Foundation’s 2020 research grant is Dr. Hongjie Yuan, Assistant Professor of Pharmacology and Chemical Biology at the Emory University School of Medicine in Atlanta, GA, and Deputy Director of the Center for Functional Evaluation of Rare Variants (CFERV) for his research project entitled:

“Rescue Pharmacology and Therapeutic Strategies to Treat Pediatric Neurological Disorders Associated with a Loss-of-function GRIN2B Variant.”

Dr. Yuan and his research team are evaluating the impact of one specific GRIN2B variant (classified as Loss of Function) on NMDA receptor function, synaptic activity and cognitive ability in a mouse model. They will also assess if the addition of substances (e.g. D-serine, D-cycloserine) to the mouse models will lessen the impact of the GRIN2B variant. If shown effective, some of the FDA-approved medications might warrant consideration in pediatric patients with GRIN2B variants. This project also includes the creation of a 2nd GRIN2B knock-in mouse line (classified as Gain of Function) to be studied in future projects.

Read more about Dr. Yuan, his project and our previously funded projects here.

Samuel Kwon, GRIN2B Foundation’s Science Director believes that, “The way that genetic variations in the GRIN2B gene disrupt the nervous system in the developing brain remains poorly understood. Animal models can provide important insight into this issue. Findings from this project will provide a strong framework for stratification of existing GRIN2B variants and potentially lead to discovery of promising drug candidates.”    

The GRIN2B Foundation Board of Directors is encouraged by the increased volume of applications received in this 2020 Grant Program. Though we could regrettably choose only 1 project at this time, we are very motivated to continue funding future research grants.

This Grant program is only possible thanks to the efforts, integrity and guidance of the GF Board of Directors, GF Medical Advisory Board & Science Director and our extended network of Scientists and Clinicians who reviewed our pool of grant applications. We are so grateful to everyone for their time and effort spent helping us select this important project.

We would not be able to award these important research grants without our community of patients, families, scientists, clinicians and people like you. Thank you for believing in and powering our mission. Make a donation today and impact vital research as we drive closer to treatments every single day.

DONATE TODAY TO CONTINUE SUPPORTING RESEARCH

Thank you,

Liz Marfia-Ash, GRIN2B Foundation Board President

 

Q&A with Dr. Tim Benke

By the GRIN2B Foundation Board of Directors and Dr. Tim Benke, University of Colorado

GRIN2B parents, you’ve got questions; we’ve got answers.

As Admins of the GRIN2B Parent Support Group on Facebook, we pay close attention to the kinds of questions that are regularly asked. Many commonly asked questions are about school supports, sleep issues for our children, and comparing/contrasting of common symptoms. Our worldwide GRIN2B community does a great job of sharing experiences and counseling one another. But often times in our group, questions come up regarding medications and what types of genetic variants the individual children have. We try to chime in when we can and direct people to the appropriate resources, but as we are an all-Volunteer Board that also works full-time, we may miss some of these important questions.

We want parents to be properly informed about topics such as further genetic testing for your child, what medications can be tried and the risks involved AND information regarding (future) clinical trials. We, at GRIN2B Foundation, along with our partner GRIN-disorder organizations are working hard to make clinical trials for GRIN patients a reality in the not-so-distant future. But we are not there just yet, and parents need to make sure they have facts from medical professionals. 

We compiled some commonly asked medical questions from our Facebook group and sent them off to Dr. Tim Benke, from our Medical Advisory Board. Dr. Benke is the Director of the Research-Neurosciences Institute at the University of Colorado as well as a Pediatric Neurologist at Children’s Hospital of Colorado. Dr. Benke is also the Principal Investigator of the GRIN Variant Patient Registry.

*Disclaimer – Any discussions that patients and families choose to have regarding the below topics should be done with a genetic counselor, genetic specialist and/or someone experienced and trained to discuss and explain these results with families and patients.


  1. How do I read my child’s genetic report?

Dr. Benke:  I think all parents should keep a binder with their child’s health information. In that binder,  create a section for the genetic report from the lab that performed the test. This report may look like this (I made this one up):

 GRIN2B c.1234G>A (p.Gly411Asp) Heterozygous, de novo, pathogenic, see comments

The “comments” section will explain that after genetic analysis, there was a spelling change at the address of 1234 in the GRIN2B gene. This change is called a “mutation” or a “variant”; “variant” is now the preferred term. This type of variant is a missense variant.

There are different types of variants. There are nonsense variants and missense variants. A nonsense variant results in only part (if any) of the protein being made. Most nonsense variants are disease causing. The CFERV website has a nice discussion on this: http://functionalvariants.emory.edu/parents/index.html)

This missense address change resulted in a switch from G to A in the DNA at that address.  This caused the protein, at protein address 411, to swap a glycine amino acid (Gly) for an aspartate amino acid (Asp). Simultaneous sequencing of the parents did not show this, meaning it is de novo or new to the child. (A new change like this can happen around the time the egg and sperm came together.) Since the child inherited two copies of the GRIN2B gene (one from each parent), the testing demonstrated that this was in only one of those copies (unable to say which one), so it is a heterozygous change. When the company looked up this change in their database and other databases, they found several reasons to state that it is pathogenic (disease causing). They may go on to say in the fine print, that with time their assessment of pathogenicity may change as databases grow. The report could also say: likely pathogenic, inconclusive, likely benign or benign. (See: https://www.invitae.com/en/variant-classification/). 

If a variant was inherited from one of the parents, the variant may not be causing disease, especially if the parent does not have similar challenges as the patient. It is possible that a variant can have “variable penetrance” due to the slightly different background of the parent compared to the child. We do not know in GRIN disorders if “variable penetrance” happens. It does happen in other genetic epilepsies such as Dravet Syndrome. Until there is more research about variable penetrance in GRIN disorders, your clinical specialist may discuss if a GRIN variant is potentially causing disease. This assessment is based on the available evidence that can change with time and more research.

If a variant is causing disease, this means that when this patient uses their genetic instructions (DNA) to make the GRIN2B protein, 50% will be made correctly and 50% will not be made correctly. The 50% not made correctly will not work the same as the other. Both will likely be present at the same time.

  1. Gain of Function and Loss of Function are terms that keep coming up in our Parent community, what do they mean?

Dr. Benke: If a protein is not working the same, it could be either doing less of what it should (Loss of function) or more of what it should (Gain of function). The genetic report will NOT typically say whether or not it is a Gain or Loss of function.

A less than perfect analogy for understanding Gain/Loss is holiday lights. If you are like me, they come out of the box every year the same way I put them in the previous year—all strung together. They are hung up and you realize some strings are working normally and others are not. In a Gain of function situation, there are normal lights next to Gain of function lights that are too bright or blinking too much. In a Loss of function situation, there are normal lights next to loss of function lights that are blinking less or not turning on at all. In both situations, the homeowners’ association is complaining.

GRINs are critical proteins involved in the creation and maintenance of excitatory synaptic connections in most regions of the brain. They are necessary for neurodevelopment, learning and memory of everything from where we just parked the car, the smell of grandma’s house, how to move, how to see, and how much appendicitis hurt when we were a kid. They are also necessary for rhythmic things we don’t think about like breathing. When they are not working correctly, gain or loss, these key processes are affected.

  1. How do I determine if my child’s GRIN2B variant is Gain or Loss of function?

Dr. Benke: Determination of Gain OR Loss of function is a completely separate process from genetic testing. It is a research-type test. It is not meant to be used to make clinical decisions due to regulatory purposes. Laboratory tests that are used to make clinical decisions (for example, a blood test that shows you are anemic and need more iron) are governmentally regulated, tested and proven to be important for making clinical decisions (see https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA). 

A computer program can sometimes guess at gain or loss of function. The gold standard is to test function in a special laboratory. In the research test to assess the functional status of a GRIN variant, a team of research scientists will test the variant in a special laboratory. Only a few laboratories in the world are capable of doing this testing. Dr. Steve Traynelis does this in his lab at Emory University in Atlanta, GA (http://functionalvariants.emory.edu/). Copies of human DNA that correspond to GRINs are kept in the lab; these are typically made by special bacteria in sufficient quantities. A specific GRIN variant is then engineered with modern genetic engineering techniques, also using these special bacteria. This engineered GRIN DNA is transferred to an “expression system” to make functional GRIN proteins. One expression system typically used is frog eggs. The function of the expressed GRINs are measured using special electrical equipment that measures the current that flows through the expressed GRIN proteins. GRIN proteins are electrical channels that turn off and on to let current flow (recall the holiday light analogy). This GRIN current is turned on when the expression system is exposed to the natural neurotransmitters that make the channel open (glutamate and glycine). The GRIN current can be reduced by natural inhibitors such as magnesium, zinc and protons.  Comparisons of variant GRINs are compared to unchanged GRINs. In these assays, if the GRIN current is bigger than it should be, the variant is classified as a Gain of function; if the GRIN current is smaller than it should be, the variant is classified as a Loss of function. If the assays are mixed (some gain, some loss), then the variant is classified as “likely” gain or loss depending on whether there are more gains or losses. If there is no change, then the variant is reported as “inconclusive”.  

  1. Why is it important information to know if my child has a Gain or Loss of function? 

Dr. Benke: It is a partially proven theory whether or not the functional status of a missense GRIN variant is clinically important. Based on our understanding of the importance of GRINS in brain function, there is a vast quantity of evidence that loss of function variants are clinically important. There is growing proof-of-concept literature that suggests this theory is also correct for gain of function GRIN variants. The initial excitement began with the work from Dr Traynelis in a patient with very severe, medically refractory epilepsy with a gain of function change whose epilepsy responded to a GRIN blocking drug (https://www.ncbi.nlm.nih.gov/pubmed/24839611). It would seem to make sense that if you have a gain of function, then blocking GRINs might help. It would seem to make sense that if you have a loss of function, then enhancing GRINs might help. However, consider this scenario:  the gain of function change caused the circuits to rewire during early development to try to correct the imbalance. As part of this rewire, the brain compensated with other GRINs that do not have the variant. By blocking GRINs, the circuits are now uncompensated again and this causes a serious side-effect like worsening seizures (or worse). A similar scenario is equally plausible with GRIN loss of function variants.

The only way to properly investigate GRIN drugs safely is part of research in an approved clinical trial. A clinical trial will determine whether a drug and what doses are safe. It will determine how often certain side-effects are observed. 

It is unknown whether or not the functional status of a GRIN variant affects symptoms. Do gain of function changes always result in epilepsy or not? If not, why not? We would like to answer this question through the registry. Please enroll in the GRIN registry by emailing Jenifer Sargent at Jenifer.Sargent@childrenscolorado.org.

When you enroll in the registry, your variant information is sent to CFERV for functional testing. When testing is complete, we will notify you and provide you with a report. Please provide this report to your clinical specialist to discuss with you. If they have questions, they can contact us to discuss (tim.benke@cuanschutz.edu). Some variants have already been analyzed and the functional reports are available on-line (http://functionalvariants.emory.edu/database/index.html).

  1. What does it mean if the functional analysis findings are inconclusive?

Dr. Benke: “Inconclusive” can mean several things, including the variant does not change function. If this is the case, the variant may actually be benign and not disease causing. This might be very important information to discuss with your clinical specialist, as it may indicate that further genetic testing may be necessary; that is a clinical decision. Importantly, the variant was not found to change function in the testing assays used. With future research and additional testing assays, an impact on function may someday be determined. This is one of the many reasons why additional research is important. Through the registry, if we find that enough patients with an “inconclusive” variant all look very similar, then we can use this to provide evidence that this variant is still likely functionally important and will drive the development of additional testing assays. (Please enroll in the GRIN registry!)

  1. Once I get the results back from my child’s functional analysis, how do I use the information to help my child?

Dr. Benke: At the moment, the best way to help your child is to make sure that you have enrolled in the GRIN registry (Please email Jenifer.Sargent@childrenscolorado.org). The functional analysis should not be used to make treatment decisions. In exceptional cases of compassionate use for medically refractory epilepsy resulting in ICU or similar hospital-based care, your treating physicians can contact us to discuss (tim.benke@cuanschutz.edu) use of GRIN drugs. 

We all hope that clinical trials will start in the very near future. As part of these trials, we think that GRIN functional status will be an important criteria for determining who can participate, as some clinical trials will use GRIN enhancing drugs and other trials will use GRIN blocking drugs.  

  1. What are some drugs that could potentially be repurposed for either a Gain of function or Loss of function result? If I try one of these drugs now, would that preclude me from participating in a clinical trial down the road?

Dr. Benke:  Use of a GRIN drug NOW may preclude you from participating in a clinical trial in the future; this is my opinion based on my experiences with clinical trials. These decisions are driven by the researchers, typically in industry or companies, that set up the clinical trial. 

FDA approved drugs that are GRIN-blocking include memantine, ketamine and dextromethorphan. They are approved for other medical uses. Use of these drugs for non-approved uses are typically not covered by insurance, including Medicaid. There are no FDA approved GRIN-enhancing drugs. There are some dietary supplements (serine, glycine) that may be GRIN-enhancing, but it is unclear and not studied to know whether or not they are safe, effective or what doses actually cross into the brain to be helpful and safe. The few studies out there are often single or a few patients, unblinded, and not placebo controlled. These are not the standard for making informed treatment decisions or for FDA approval.

If individuals try things outside of a clinical trial, then how will the rest of the community benefit from this knowledge? How will the community be able to evaluate and trust the knowledge available? The current GRIN registry is trying to collect this information from the community, but this is not the data that would be considered by the FDA to approve a drug. This data is only to support efforts to consider and provide data to seek funding for a clinical trial. Please enroll in the registry by emailing Jenifer.Sargent@childrenscolorado.org.

  1. Why are clinical trials important and what is the general process?

Dr. Benke: We need clinical trials to understand which drugs are safe and effective. They are needed so that your clinical specialist can feel confident that what they are recommending to you will be safe and effective. Your clinical specialist needs to understand the side-effects that are common to a drug in order to let you make an informed choice when you weigh together the risks and benefits of a therapy. We need clinical trials to get FDA approval for drugs so that their cost can be covered by insurance and Medicaid.

A clinical trial is the research process by which subjects/caregivers consent/assent to participate in a defined clinical research study designed to produce information that can be used to understand (study) or help (trial) the population as a whole. This data is peer-reviewed and published to advance the knowledge and effective and safe treatments of the disease. Trials are interventions.

You do not HAVE to participate in a clinical trial unless you WANT to participate: participating involves consent (in some cases using de-identified data you “opt out” versus “opt in”). You can WITHDRAW at any time. A review board must approve the trial before any subjects are contacted or enrolled; international rules of standards and ethics are applied. 

There are phases to trials:

Phase 1: Testing healthy volunteers, multiple doses. May be in patients with advanced stages of a disease or diseases with no known treatments.

Phase 2: Testing on patients for efficacy and safety. (Where GRIN drugs will likely start.)

Phase 3: Confirmatory: Testing on patients for efficacy, effectiveness, and safety

FDA typically will approve for use after Phase 3. This process can take years.

Clinical trial definitions:

Placebo controlled:  a placebo (“sugar pill”) is used to make sure the effects are real

Randomized:  Who gets placebo or drug is a flip of the coin.

Double blind: Subjects and local Study personnel do not know who is getting drug.

Open Label:  Everyone is getting drug and there is no blinding

Cross-over:  Those getting drugs then get placebo and vice-versa. Usually Randomized and Double blind too.

Extension:  Access to drug after trial ends (usually an open label continuation of the trial).

Gold standard that FDA uses to approve drugs: randomized, double-blind, placebo-controlled

 

 

Celebrating Rare: The GRIN2B Podcast, Episode 4

By Guest Blogger, Phil Ash, GRIN2B Foundation Board Member

Hello! This is Phil Ash, teacher, father, Board Member of GRIN2B Foundation, and the host of Celebrating Rare: The GRIN2B Podcast. In this episode, I welcome in a new decade by recapping and putting a bow on 2019. What a year it was for our Foundation! We attended events, raised a lot of money and, perhaps most importantly, we completed our first research grant cycle! This past fall, we awarded $56,457 to Dr. Caitlin Hudac, an Assistant Professor at the University of Alabama. Dr. Hudac joins the podcast to tell us all about her exciting research regarding GRIN2B-Related Neurodevelopmental Disorder! During 2020, Dr. Hudac will be studying 25 GRIN2B patients and their EEGs in order to determine specific biomarkers related to the GRIN2B gene. Not sure what that means? Neither was I! Check out the podcast to hear Caitlin break it all down for us. GRIN2B Foundation is very excited about this work and the opportunities it will provide for furthering research into GRIN2B. 

Dr. Caitlin Hudac, GRIN2B Foundation’s 1st Grant Recipient

Read more about Dr. Hudac’s study here and learn how you can enroll.

I hope you enjoy this episode and be on the lookout for future episodes this year featuring additional parents, researchers and doctors. As always, if you have comments or suggestions for future topics, or are interested in being a guest on future episodes, please send an email to phil.ash@grin2b.com or send a tweet to @grin2bsyndrome, using the hashtag, #CelebratingRare.

To further protect myself from any unintended mistakes, each episode will have the following written disclaimer when you click on the link:

PODCAST Disclaimer: While I make every effort to broadcast correct information, I am still learning. I make every effort to double check my facts, but realize that medicine is a constantly changing science and art. I am simply sharing my views and personal experiences as a GRIN2B parent. I am not a medical professional. I welcome any comments, suggestions, or correction of errors. This entire disclaimer also applies to any guests or contributors to the podcast. Under no circumstances shall Phillip Ash, GRIN2B Foundation, any guests or contributors to the podcast, or any employees, associates, or affiliates of GRIN2B Foundation be responsible for damages arising from use of the podcast.