Vol. XX - April 2023 | Email Us | CDGCARE.org
In this Issue
  • Parent & Project Spotlight: Project GRACe
  • Emmett's Legacy Fund Awards
  • Research & Partner Updates
  • Advocating for Our Community
  • World CDG Organization Conference & Resources
  • May 16th is World CDG Awareness Day!

Project GRACe: The Birth of a Patient Driven Research Project into the Neuroscience of CDG
Hello CDG Community! My name is Meral Omurtag and I am a physician and mother of two girls ages 11 and 13. My oldest daughter was diagnosed with CDG at 4 months of age.

This is the story of how I met Dr. Sarah Ackerman and launched Project GRACe (Glial Research in ALG8 CDG), a research project that aims to develop CDG animal models to further the understanding of the neurological manifestations of CDG and to use the knowledge gained and models developed to look for potential treatments.

In April 2022, I went to St. Louis to celebrate my 25th medical school reunion at Washington University. It was so great to go back to a place and see people from a vastly different time in my life—before marriage, before kids, before CDG. Little did I know that in addition to having a great time visiting old friends, my trip would lead me directly to a wonderful new partnership with a young neuroscientist!

I had just attended the 2022 CDG family meeting in San Diego hosted by CDG CARE and Sanford Burnham Prebys. My mind was abuzz with all the scientific advances that had developed in CDG in just a few short years. I took this sense of inspiration and excitement with me to my reunion. There, I went to a keynote speech given by prominent neuroscientist, Jonathan Kipnis, which was tantalizingly called “Can We Rejuvenate the Brain?” Given that my child’s CDG primarily affects her brain and nervous system, I definitely wanted to see what he had to say! 

The short answer to the question of his provocative title is, NO. We cannot at this time rejuvenate the brain.  But, based on research that he is doing, he believes that by studying and understanding the role of the lymphatic system and glial cells of the brain, we can find ways to treat or prevent brain disorders. Dr. Kipnis likened the neurons of the brain to a race car. The less studied glial cells, he likened to the pit crew responsible for keeping the race car functioning well and repairing any breakdowns. Even if the car is in perfect shape, it can’t run well if the repair crew isn’t able to do its job!

As he spoke, I had a profound sense that glial cell dysfunction could be directly implicated in the neurological symptoms my child experiences. Although CDG is a glycosylation disorder, how is the disordered glycosylation impacting her neurological function? Perhaps glycosylation defects lead to breakdowns in glial cell function.

So, I went up to Dr. Kipnis after his talk and after a brief introduction about why I was there I told him I wanted to make CDG animal models with a neuroscientist. He asked if there were any researchers already working on CDG, so I mentioned the NIH funded FCDGC. After that we corresponded by email, and he introduced me to Sarah Ackerman, a young researcher who had just joined the WashU faculty.

Dr. Ackerman is absolutely amazing! As a parent, in this strange role of speaking to a basic scientist about basic science research and my child, I found that she listened to me and my concerns with a kind and compassionate ear, truly seeking to understand my daughter’s illness and my goals for this research. She reflected back what I said and responded to it with her expertise and suggestions. After our conversation, she developed a proposal for a research project designed to answer the basic questions I was asking. And then, when her lab opened in July, Project GRACe, developed through a fiscal sponsorship with CDG CARE, began!

One year since I started down this path, I am so grateful to have met Sarah Ackerman. It’s wonderful to have a brilliant, kind and communicative researcher with whom to share this journey. I’m happy to report that some initial technical difficulties with the gene editing process have been resolved, and data will start to come in soon! Stay tuned!
Emmett's Legacy Fund helps families around the world obtain much needed medical equipment
CDG CARE and the Nguyen family are delighted to share that our third round of funding through Emmett's Legacy Fund is providing over $25,000 of much needed medical equipment and support to 14 families located throughout the USA, Canada, Mexico and Brazil!
Life with CDG is tough. We understand the many challenges that arise on a daily basis, and our aim is to alleviate some of these hardships. We will be sharing additional details on the specific items that have been supported in our Emmett's Legacy Fund social media series which will launch on the CDG CARE Facebook Page this summer!

To learn more about Emmett and his life, visit www.lifebyemmett.com and for additional information about PIGA-CDG, please visit www.PIGA-CDG.org
FCDGC Natural History Study Update
The Frontiers in CDG Consortium (FCDGC) has now enrolled more than 300 patients to the CDG natural history study! The largest group is 92 patients with PMM2-CDG followed by ALG13 with 15 patients.

From the natural history study participants, the FCDGC team is planning clinical trials to include 14 patients who are enrolled with SLC35A2-CDG, 12 with PGM1-CDG, and 4 with NGLY1 defect.
FCDGC Natural History Study Identifies Potential Biomarkers for Diagnosis and Prognosis in ATP6AP1-CDG
The FCDGC Natural History study recently published finding biomarkers of potential diagnostic (identifies individuals with the disease) and prognostic (predicts how the disease will progress) importance in ATP6AP1-CDG.

In the report, FCDGC summarized 11 new patients with ATP6AP1-CDG, including reports of 3 who underwent successful liver transplant for the liver disease characteristic for the condition.

This brings the number to 30 ATP6AP1-CDG patients reported to date. The full study can be found HERE: https://pubmed.ncbi.nlm.nih.gov/36651831/

This study was also highlighted on a podcast with the lead FCDGC authors and can be listened to at any of these sites:

Soundcloud: HERE
Apple: HERE
Spotify: HERE
The FCDGC Natural History study has recently expanded internationally. We want to thank all of the families who are currently participating in this international study. We anticipate that the coming years will provide us with many additional important insights that will improve the care of all CDG patients. If you are interested in joining, see the FCDGC website for contact details of the study site nearest you: https://www.rarediseasesnetwork.org/fcdgc/sites.
The role of PGM1isoform 2 in PGM1-CDG: One step closer to genotype–phenotype correlation?
Silvia Radenkovic, Jon K. Laerdahl, Paul H. Backe, Eva Morava
First published 23 February 2023: Recent editorial published by Radenkovic et al, 2023 focuses on the PGM1 protein isoform 2 (PGM1-2) and its clinical relevance in PGM1-CDG. 

Recently, Backe et al, 2020 have reported on several differences betwen the two PGM1 isoforms: PGM1 isoform 1 (PGM1-1), which is expressed in all the tissues, and PGM1-2, which is expressed only in the muscle. Due to the lack of phenotype-genotype correlation and common muscle and cardiac presentation in PGM1-CDG, the authors suggested that PGM1-2 isoform could play a role in the clinical severity of PGM1-CDG. 
In the present study, Radenkovic et al investigated the correlation between the PGM1-2 and cardiac/muscle presentation in PGM1-CDG by classifying all reported PGM1-CDG patients based on the isoforms that were affected. PGM1 pathogenic variants affect either PGM1-1, PGM1-2 or both isoforms. The authors found that simultaneous cardiac and muscle involvement is occurring more often in PGM1-CDG patients that have both isoforms affected. The findings point towards the importance of considering organ-specific transcript differences while assessing genotype-phenotype correlations in disorders where genotype-phenotype correlations are lacking, such as PGM1-CDG. https://doi.org/10.1002/jimd.12601
Cure SRD5A3 Research Update: Low-Dose Statins as a Potential Therapy for SRD5A3-CDG
Cure SRD5A3 and the Sappani Foundation are excited to share the latest breakthrough from our drug repurposing research program!
In collaboration with Modelis, we have developed an SRD5A3 worm avatar and screened over 4,000 FDA-approved drugs, bioactives and natural products for compounds that rescued the movement phenotype in the worms. We identified over 50 compounds which improved the phenotypes of the worms, including several that indicate HMG-CoA reductase as a promising therapeutic target. In collaboration with the Pandey and Morava labs at the Mayo Clinic, we have determined that the ratio of dolichols to polyprenols is lower in SRD5A3-CDG patient fibroblast lines than control lines, which may play a critical role in disease pathology. Statins, which are a group of FDA-approved cholesterol-lowering drugs that inhibit HMG-CoA reductase, may restore the ratio of dolichols to polyprenols in SRD5A3-CDG. We are currently validating the effectiveness of atorvastatin and other HMG-CoA reductase inhibitors in both worm and cellular models of SRD5A3-CDG. To learn more about our drug repurposing research and how low-dose statin therapy may benefit SRD5A3-CDG patients, please check out Perlara’s Substack here!
If you are a physician or a family member of someone with SRD5A3-CDG and would like to learn more about drug repurposing for SRD5A3-CDG, please contact us at research@sappani.com
Long-term outcomes in ALG13-Congenital Disorder of Glycosylation
Rameen Shah, Christin Johnsen, Beth A Pletcher, Andrew C Edmondson, Tamas Kozicz, Eva Morava
ALG13-CDG is an X-linked congenital disorder of glycosylation. As the population of individuals with ALG13-CDG is aging, it is imperative to understand the long-term outcomes of ALG13-CDG. Thus, we collected natural history and literature data from patients with confirmed ALG13-CDG older than 16 years old. Across the literature and our natural history data, we found six patients older than 16, all of whom were females. All patients displayed seizures, weak muscle tone, intellectual disability, and speech and developmental delay. Out of the four patients that attempted a high-fat diet, 3 showed improvements in seizures. All of the patients were mobile but had mostly absent speech. Uncoordinated muscle movement, nerve damage in the hands and feet, gastrointestinal symptoms, and hearing loss in one ear were some rare symptoms that we identified in our patients. Also, a reduced ability to form new bone was found in one patient, and curvature of the spine was found in another. To conclude, long-term outcomes in ALG13-CDG are characterized primarily by neurological, skeletal, and gastrointestinal symptoms. https://doi.org/10.1002/ajmg.a.63179
CDG CARE Engages FDA in
Patient Listening Session
On January 30, 2023, CDG CARE engaged the U.S. Food and Drug Administration (FDA) in a Patient-Led Listening Session to share the burden of CDG and the needs of our community.

During the session, representatives from CDG CARE and the parent community shared their personal experiences of living with CDG, their diagnostic challenges, and the physical and emotional toll that CDG has on their families. Given that there are no FDA approved treatments or a cure for CDG, the panel thoughtfully expressed what would be meaningful impacts when it comes to a potential therapy.

Through this opportunity, parent and professional advocates joined together to educate the FDA on CDGs and we expressed our commitment to bring the patients’ perspective to every stage of therapeutic development and approval.

This meeting was only the beginning of an ongoing conversation with the FDA. We look forward to sharing more updates as we move this important work forward.

To read the full FDA Session Summary: Download the PDF HERE
Stand United for CDG!
May 16th is World Congenital Disorders of Glycosylation (CDG) Awareness Day!

Calling all Families, Caregivers, Communities and Professionals to support CDG!

We invite you to join the 8th annual World CDG Awareness Day Campaign!

World CDG Awareness Day is an annual event that provides international focus for patient groups and families living with CDG. It is an opportunity to raise awareness, influence change, promote timely disease diagnosis, and improve access to better standards of care and management. Since World CDG Awareness Day initially launched in 2016, more than 325 events have taken place around the world.

Through the support of our donors, CDG CARE has raised $1.3 million dollars to date and has funded more than $675,500 toward research contracts to advance the diagnosis and treatment of all CDGs! By Standing United for CDG, we have also been able to assist 47 CDG & NGLY1 families with more than $112,500 in direct patient financial assistance. Our community has so much more to look forward to on the horizon, so we encourage our community to join this effort to raise awareness and funds to advance CDG & NGLY1 research, therapies and treatment strategies that will improve the lives of children and young adults diagnosed with CDG.

This year's campaign, Stand United for CDG, will run through May 16th. So, if you are organizing or running in a 5K run/walk, asking families to donate to your favorite cause for your birthday, or doing a tribute to a loved one... we have got you covered!
Give Lively is an easy-to-use fundraising platform for nonprofits. Just visit and share CDG CARE’s "Stand United for CDG" Fundraising page, and/or create your own campaign by clicking "I Want to Fundraise for This" and create a custom fundraiser for our cause, with your own family photos! To visit our page, and get started, simply Click HERE.

We encourage our social media followers to keep up to date on our progress by 'Liking' the CDG CARE Facebook Page and 'Sharing' our posts as we paint the USA and the entire World GREEN showing support for May 16th – World CDG Awareness Day!
CDG Awareness Day Events Down Under!
Shepparton, Victoria, AUS - The Annual CDG Awareness Day Walk is happening again this year for our CDG Strong family! The walk will be held Sunday, May 21st at 11:00am in our hometown of Shepparton. With Louis' nearest and dearest by his side, we will walk around Victoria Park Lake in Shepparton and then enjoy a BBQ lunch- all while creating a sea of green!

We anyone in the surrounding area to join us, we would love to see you there!

Melbourne, Victoria, AUS - Additionally, there is a walk happening on May 21st at the same time of 11am in Melbourne at Darebin Parklands. Any CDG Families and friends are welcome to join that- just look for the green balloons! As always, this day is all about raising awareness about all things CDG and celebrating our favorite CDG Warrior Louis! Whether you can come to these events or not, we would love if everyone would wear green on CDG Day and help us PAINT THE WORLD (or our small part of it) GREEN!

To learn more about CDG Australia events, visit our webpage HERE!

And if YOU have events happening in your community, please let us know so that we can share the momentum at info@cdgcare.org
World CDG Organization:
Education & Resources
The 6th World Conference on CDG
There are 3 educational tracks under the scope of the “6th World Conference on CDG”:

The 6th World Conference on Congenital Disorders of Glycosylation (CDG) for Families and Professionals promotes the exchange of information and experience among people living with CDG and related stakeholders around the world.  

To view the agendas, click HERE

  • About the online “World Think Metabolic, Think CDG Academy”: The virtual pre-conference sessions are delivered in English. By securing your attendance and actively participating during the virtual pre-conference sessions and the face-to-face conference, you will achieve the “CDG Expert Diploma”. Stay tuned!

  • About the 2 In-person events:
  • The “First World CDG Advocacy, Policy and Leadership Academy”: If you are beginning to think about advocacy and do not have any experience so far, do not worry, the “First World CDG Advocacy, Policy and Leadership Academy” offers a range of virtual and in-person sessions to help you. This academy is tailored for leaders of CDG patient groups and their advocates and any family members who wish to become successful advocates. Participants will acquire knowledge and skills to participate in research and drug development activities with all stakeholders in a collaborative and global mindset.
  • The “6th World Conference on CDG”: Offers several sessions dedicated to clinical trials, access to treatments and care and management for CDG.
World CDG Magazine
The World CDG Magazine, centralizes information in lay language about topics considered of interest to our community.

Among the topics in this issue, you will find:
1) News from the CDG Patient Groups around the world and CDG Ambassadors
2) Amazing news about care and management
3) Advances in advocacy and policy that impact CDG
4) News from the industry and CDG research networks
5) Recent published Biomedical publications
6) Updates about events and trainings to upskill our CDG community
7) Getting ready to celebrate the World CDG Awareness Day
8) Announcements related to “World Think Metabolic, Think CDG Academy”, “World CDG Advocacy and Leadership Academy” and “6th World Conference on CDG”

Go to: https://worldcdg.org/index.php/resource-magazine/world-cdg-magazine and stay tuned for the next World CDG Magazine !