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GRIN2B Foundation Awards $56K in Inaugural Rare Genetic Research Grant

GRIN2B Foundation is pleased to announce an award of $56,457 to one post-doctoral research effort in its 2019 inaugural research grant initiative to promote scientific understanding of the ultra-rare genetic condition known as GRIN2B-Related Neurodevelopmental Disorder.

The grant is designed to support research in the 2019 funding cycle on changes to the GRIN2B gene, which have been linked to Intellectual Disability and symptoms of Autism in hundreds of children.

The recipient of GRIN2B Foundation’s 2019 research grant is Dr. Caitlin M. Hudac, an Assistant Professor at the University of Alabama for her research project entitled, “Linking Brain and Behavior: A GRIN2B Biomarker.”

Dr. Hudac will link a promising electroencephalography (EEG) based candidate biological indicator (“biomarker”) to clinical behaviors of children with disruptive GRIN2B mutations. EEG biomarkers will aid in the interpretation of GRIN2B function, by capturing real-time pictures of the neural process by which children with GRIN2B mutations think. This candidate biomarker can potentially be used as a clinical outcome assessment. This project will teach us about how brain markers of attention relate to the clinical behaviors observed in children with disruptive GRIN2B mutations. Testing a brain-based biomarker will prepare researchers for clinical trials and other treatment-focused research. To conduct her research, Dr. Hudac will perform EEGs on various research subjects with GRIN2B-Related Neurodevelopmental disorder.

The original scope of this project was to study 10 research subjects. After a rigorous review process, it was determined the project would be more successful with a larger cohort of 25 patients. The team at GRIN2B Foundation worked with Dr. Hudac to modify the proposal for a larger scope and agreed to increase funding from the original grant amount of $40,000 to $56,457.

Dr. Hudac works at the University of Alabama in the Center for Youth Development and Intervention (CYDI) and the Department of Psychology. Her program of research examines how the brain develops from birth through adulthood with a focus on potential areas of divergence associated with neurodevelopmental disorders (e.g., autism spectrum disorder, ASD; intellectual disability, ID). 

Read more about Caitlin and her research study here.

Samuel Kwon, GRIN2B Foundation’s Science Director, was instrumental in guiding the GRIN2B Foundation Board of Directors through this inaugural grant cycle.

Kwon says, “Although GRIN2B-Related Neurodevelopmental Disorder is caused by variations in a single gene, multiple brain areas are affected because the product of GRIN2B gene is important for communication between brain cells in several different areas. Developing effective therapeutic interventions has been challenging due to the lack of a reliable indicator that captures an overall state of the brain during a specific behavior. Caitlin Hudac will combine EEG and a sensory processing task in human GRIN2B patients to develop a novel biomarker based on brain activity. Such development will enable a robust clinical outcome assessment and provide a link between behavioral deficits and brain activity in human patients.” 

In the near future, Dr. Hudac and GRIN2B Foundation will begin seeking out families who may wish to participate in this study. Potential subjects must be willing to travel to Alabama for the study. Travel stipends will be available. Additionally, GRIN2B Foundation will ask Dr. Hudac to travel to Chicago next Summer for the recently-announced Family Weekend, where she can work with additional research subjects.

If they haven’t already done so, families should register with GRIN2B Foundation’s Contact Registry to ensure they receive all updates on this important study.

GRIN2B Foundation has seen the affected patient community grow from a mere handful to over 300 in the last few years. “This is a very exciting and important time of growth for both our organization and our extended GRIN disorder patient community,” said Liz Marfia-Ash, President of GRIN2B Foundation. “We believe our research grants, combined with our close collaboration between researchers, our patient community and our growing family of GRIN gene disorder patient groups & organizations will be critical to finding treatments and cures.”

This Grant program is only possible thanks to the efforts, integrity and guidance of the following groups, organizations and individuals:

GF Board of Directors 

GF Medical Advisory Board & Science Director 

Dr. Katherine Roche, NIH

Kristin Goltry, NIH

The International Foundation for CDKL5 Research

The FamilieSCN2A Foundation

SETBP1 Society

“We have worked aggressively to raise awareness and fundraise, and our success is directly attributed to an engaged community of GRIN2B parents, families and friends who have rallied around us. We hope this research study is the first of many we can help foster through our funding program.” – Liz Marfia-Ash

 

When Vacations and GRIN2B Research Collide

By Guest Blogger, Phil Ash, GRIN2B Foundation Board Member

Vacation. Hotels. Kids. Time away. These phrases evoke feelings of fun, activities, and relaxation for parents and families desperate for a break from the rat race. It’s harder for me to feel the same way. Vacations for my family are the ultimate wild card. I never know how our three kids, ages 2, 6 and 9 are going to react to a change in the routine. My wife and I have experienced getaways that swing wildly from fun to chaos, and back. Some have gone okay, others have been cut short. Not knowing how vacations are going to go or if our non-verbal daughter is going to enjoy herself are big stressors for me.

Our recent family getaway at the end of June was different. We took a 4 hour road trip from Chicago to the University of Michigan, Ann Arbor to visit the lab of Samuel Kwon, one of many GRIN2B researchers. Sam is an Assistant Professor and, according to his website, “studies mechanisms underlying neuronal dynamics and plasticity.” Don’t worry, we didn’t really know what that meant either. 

We had met Sam and his wife at the GRIN2B Foundation Family Conference last year and had kept in touch ever since. My wife, Liz, our Board President, came up with the idea to combine a family vacation with a visit to the University of Michigan, and Sam graciously agreed to give our family and the Crider’s (another GRIN2B Family) a tour of his lab. For us, this was more than just an overnight trip. We were going on a journey to see first-hand, important research regarding GRIN2B-Related Neurodevelopmental Disorder. What’s more, we would be going with a built-in support system in the Crider family: Brittaney, Mike and their two kids. 

During most vacations, our family is always the outlier. When things go wrong or when breakdowns occur, it can feel like we’re alone on an island. But having another GRIN2B partner family and a group of passionate researchers excited to see us calmed my anxiety and helped create a great getaway for everyone in our family. Like dorks, every member of our two families wore our GRIN2B t-shirts. Everywhere we went, people asked us questions about our “bee” shirts.

Our two families arrived at the University of Michigan and were met by Sam’s undergraduate research assistant (also named Sam!) who took us to the lab. Sam and his assistant gave us a brief presentation regarding their work and then took us on a tour of their impressive, extensive laboratory. 

If I’m being honest, the minutiae of what Sam is doing was well over my head, and for good reasons. The research presentation was given in a small conference room with 5 children all under the age of 9; including our 2-year-old son who spent his time running around doing 2-year old things! In spite of the distractions, I was humbled by their passion and excitement to see us. Their PowerPoint presentation included citations from our website, www.grin2b.com. This may not seem like a big deal, but as an educator who recently finished his Masters Degree, it was so satisfying to see a group of brilliant researchers citing a website I helped create. The lab was extensive and it was a bit strange actually seeing the research mice. (Don’t worry – we’ll share more specifics about Sam’s lab towards the end. Keep reading!)

Sam and his family could not have been more gracious and patient with us. They were excited to speak with us and spend time with our families. Following the tour, they took us to lunch. After we bid them goodbye, the balance of the day was our own. Our family and the Criders went to a children’s indoor playground, had pizza in the hotel and then spent some time with the kids by the pool. Normal family stuff, but for me, this time it was free from the usual anxieties. Our kids behaved wonderfully, but having another family with us that also experiences the highs and lows that come with a GRIN2B diagnosis made all the difference. 

Hopefully, this was just the first of many research road trips we will take!

If you were thinking you’ve heard of Sam Kwon before, it’s probably because he recently became GRIN2B Foundation’s Science Director! We were so impressed with his passion and expertise at our visit and knew we’d finally found the missing piece of our organization. Our Board was thrilled to offer him the position earlier this month, and he is already more than proving this worth by organizing our first grant cycle. Read Sam’s bio here http://grin2b.com/medical-advisory-board/

Between the science being over our heads and having to wrangle 5 children, ages 2-9, none of us adults were really able to take notes during this visit. We thought it was best for Sam to explain his work himself so here are his answers to our follow-up questions:

Samuel Kwon, PhD

How long have you worked for the University of Michigan? Tell us a little bit about your lab.

I have been working at the University of Michigan since January 2018. That is when I started my own lab after several years of postdoctoral research at Johns Hopkins. The research in my lab focuses on how nerve cells in the brain process sensory information and how this process is altered in humans carrying mutations in autism-related genes. My lab is especially interested in how brain cells change over time as a new knowledge or skill is learned. This is called ‘neural plasticity’. We leverage the fact that mammalian brains are similar across species and use mice as a model organism to study neural plasticity in the cerebral cortex of health and disease. We can train mice to perform simple behavioral tasks while monitoring and manipulating individual brain cells using state-of-art microscopic tools. 

How did you become interested in studying GRIN2B?

In April 2018, I had the privilege to attend the scientific meeting organized by Simons Foundation, which provides a major support for my current research. The meeting was heavy on genetics of different neurodevelopmental disorders. Although I am not a geneticist, it was obvious to me that a set of genes required for proper signaling between nerve cells were strongly linked to various neurodevelopmental conditions. Grin2B was consistently one of them, but I didn’t look into it any further. Two months later, my wife and I found out that her 3.5-year-old nephew in South Korea had been diagnosed as having a Grin2B neurodevelopmental disorder. It took three years to find out since the time where his parents first started noticing severe developmental delays such as motor deficits and intellectual disability, because a Grin2B mutation is extremely rare in South Korea or anywhere in the world. To connect with other GRIN2B families, I attended the first GRIN2B Foundation Family Conference in September 2018. It was an invaluable experience for us at both personal and scientific levels. By talking and listening to other families, I learned a lot about the challenges that GRIN2B parents face daily as well as practical tips that could improve the quality of life of both parents and their children. The conference included research presentations by world-renowned neuroscientists. Inspired by these presentations, I decided to launch a research project in my own lab to investigate how Grin2B mutations impact neural circuits in the brain.

Tell us (in layman’s terms) about your work on GRIN2B.

A common hallmark of children with GRIN2B neurodevelopmental disorders is a motor dysfunction. We aim to understand how variations in GRIN2B impact the neural circuit for motor function using mouse models of GRIN2B variants. Specifically I will focus my effort on determining the time points when therapeutic interventions for motor dysfunction need to be focused. From there, I will expand our research directions toward a better understanding of how Grin2B mutants contribute to specific pathological hallmarks including sensory and cognitive impairments. We hope that this research would accelerate the availability of treatments for Grin2B-related syndrome. 

What do you hope to learn from your mouse models?

We have been using a mouse model in which the level of GRIN2B can be reduced in specific brain cell types. This is called a ‘conditional knock-out’ mouse. I obtained this model from Professor John Gray at UC-Davis. One of the experiments being performed in my lab is to reduce GRIN2B in different areas of cerebral cortex and test its impact on motor function. In parallel, we are creating a ‘conditional rescue’ mouse in which GRIN2B can be switched on in specific brain cell types by the experimenter, at any point in time throughout development. With these resources, we would be able to experimentally modulate GRIN2B in specific brain areas at different time points and monitor its effects on behavior and brain function in living mice. These efforts will enable us to determine if there is a ‘critical period’ in which a normal level of GRIN2B is essential and will provide an important scientific framework for therapeutic approaches.

 

GRIN2B and Gratitude

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

Recently, about twenty people from our GRIN2B parent community participated in a webinar hosted by Simon’s VIP Connect (a research initiative studying many different genetic changes associated with developmental delay and Autism). During this webinar, we listened as a doctor from Simon’s VIP presented a summary of the data on the families who have signed up for their GRIN2B registry. For me, this experience was simultaneously HEARTWARMING, ENCOURAGING, FRUSTRATING and MIRACULOUS.

HEARTWARMING to hear each parent introduce themselves. We have bonded pretty intensely in our private Facebook group by sharing all the highs and lows of dealing with this mysterious rare condition, and we have become a little family; a family that is spread all over the world. To finally hear the voices of other parents on this same journey and to participate in this group event was surreal.

ENCOURAGING because this is just the beginning. We will have more webinars. Our numbers will increase. More research will be done. But we, the parents, have to push for this. We have to be proactive and drive the research. Though only about twenty families have completed the registration process through Simon’s VIP, I, along with the rest of the GRIN2B Foundation board members, will continue to encourage more families to register. Is the registration process time-consuming? Yes. But it’s so important. The data collected in our GRIN2B registry will be available to any interested researcher. And you receive Amazon gift cards for completing the registration process. My kid is getting an extra sweet Christmas present this year thanks to these gift cards.

FRUSTRATING because I know we want answers, we want treatments, we want to understand how our kids’ brains work and what interventions we can use to best help them. I can’t speak for every parent, but I know I am hungry for information on how to best help my daughter. Unfortunately, there is not enough data available to provide us with concrete answers right now. With this being our first webinar, the data presented was pretty basic for those that are not new to this diagnosis. You guys, I get it, this SUCKS. I have had days (a lot lately) where I can’t decide if I’d rather put my fist through a wall, drink several glasses of wine or stay up all night researching GRIN2B and how we can best move forward. I have this weird dual personality where, on the one hand, I hate that every doctor appointment I go to feels somewhat pointless. All anyone can do is guess as to what is going on, and I leave each appointment with half a dozen things to research. But on the other hand, I get it. Doctors and researchers aren’t magical, all-knowing miracle workers. GRIN2B is in its infancy of being studied, diagnosed and understood. I do believe that most of our doctors are doing their best to help us, but, in the end, it’s not their kid, and they don’t have the sense of urgency we have. It’s hard and unbelievably unfair.

  MIRACULOUS because we have come SO FAR, YOU GUYS. Seriously. Fellow GRIN2B parents, do not lose hope. Well, actually, I take that back. It’s okay. Lose hope, but just do it for a day or a week. And then keep going. Three years ago, on the day after Thanksgiving, my husband and I sat in our Geneticist’s office and received the news of the GRIN2B diagnosis. We were told there were only about ten others with this mutation. There was no support group, no Foundation, no website, no blog posts, not even a lousy pamphlet to read. I knew nothing back then about just how rare a disorder could actually be and that day changed everything.

Look at where we are. Look at where we started. – Hamilton

As one of the Admins of our Private Parent Group on Facebook, I can tell you that more families are joining every week, which means more individuals are being diagnosed. Our numbers are growing. I totally respect that not everyone is comfortable with participating in Research. BUT BUT BUT we cannot expect or hope for change or answers by doing nothing and waiting. It was pointed out during the webinar that the gene that causes Cystic Fibrosis was first discovered in 1989. The first FDA approved treatment, addressing the underlying cause of CF, was not until 2012. Let’s do the math. That’s after 23 years of research. Science is definitely moving faster than it was in 1989, but, we cannot sit on our butts and do NOTHING. I’m saying (well, really writing) all of this in my most stern, but affectionate “Mom” voice. We have a LOT of work to do.

I know this is not easy, and the road ahead can seem bleak at times. I KNOW you’re all exhausted and worried because I am too. I have never been one of those happy-go-lucky people who looks on the bright side. I’m a worrier at heart, and I have had to re-train my brain to focus on the positives since the diagnosis.

As we’re wrapping up Thanksgiving weekend here in America, let’s reflect on what we have to be thankful for:

  • A growing community of GRIN2B families from all over the world, committed to supporting each other. Just three days after receiving my daughter’s diagnosis in 2014, I found my first fellow GRIN2B mom, Donna Dunn, through another special needs Facebook group, and I was the first person to join her in the private GRIN2B parent group she had created. Now, three years later, we have over 100 families in our group.
  • We will soon be raising $$$ for GRIN2B research, support and education for families. We are still waiting to receive our official 501c3 non-profit status, but look for ways to donate/get involved in 2018.
  • We are tentatively planning a GRIN2B family conference (with medical speakers) for Fall 2018. We’ll share more details early next year.
  • Our first GRIN2B Awareness month in March!

As our Board of Directors and our community of GRIN2B families looks to the future, we need to remain patient and organized. It’s easy for me to sit here and type these nice, inspiring words, but I totally get that in our day-to-day lives, it is hard to remain patient. On those days my daughter is struggling, and I am spinning around in circles trying to find solutions, I admit I sometimes want to quit. I pull my hair out and curse GRIN2B and all these damn unknowns. But then I keep going, because really, what is the alternative? Our Foundation is getting off to an admittedly slow start, but that’s life. If you have any suggestions for ways to improve the website, the organization of our group or have any leads on fundraising or research, we welcome your ideas. Feel free to email myself or any board member at info@grin2b.com or message me through Facebook.

To my fellow GRIN2B parents, I have not been very active lately within our Parent Support group due to my even-more-crazier-than-usual life, but please know that I am grateful for each and every one of you. Now, enjoy what’s left of your holiday weekend, get some rest, eat all of the leftovers and get ready to kick some GRIN2B butt in the years to come.

P.S.

  1. PLEASE, PLEASE, PLEASE join our GRIN2B registry at Simon’s VIP Connect. It’s so important that we get more data for our registry to share with Researchers. If you’re still not sure what the heck Simon’s VIP Connect is and how it relates to GRIN2B, click here.
  2. Did you miss the webinar? Like our Facebook page and keep watching for updates. As soon as the recording is available, we will share it there.
  3. Sorry for so much all caps in this post! I generally do not approve of excessive use of capitalization, but man oh man, this post really called for it.