The Association for Creatine Deficiencies is committed to fostering and supporting a thriving research community for Cerebral Creatine Deficiency Syndromes (CCDS). Creatine Transporter Deficiency has no treatment. GAMT and AGAT deficiencies have treatments that can be improved especially when children are not diagnosed early. As parents, our motivation to see treatments for our children is urgent and unstoppable.

Our research strategy is to fund, build, and share tools and resources that can accelerate the discovery of treatments for children living with creatine deficiencies. Our approach is collaborative and relies on open science to shorten the timelines required for development. As a parent-led research organization, our responsibility is to support the widest range possible of relevant research efforts in the scientific community, including biotech and pharma, in order to maximize our chances of getting treatments.

What we do:

  • Collect de-identified data from our CreatineInfo Patient Registry
  • Collaborate with researchers academic or industry to support basic, translational, and clinical research for all three CCDS. 
  • Fund research through grants and fellowships.
  • Enable access to development tools (biosamples, mouse models, etc.
  • Act as a liaison for connecting various domain experts (academic or industry) to speed up progress.
  • Organize scientific meetings (see Virtual Conference 2020).
  • Educate our families on science and research topics relevant to CCDS (see quarterly Creatine Decoded essays)


Current Projects and Collaborations:

CCDS Gene Therapy Consortium

Gene therapy is an exciting research area that holds the promise for treatments in many rare diseases. Both Creatine Transporter Deficiency and GAMT deficiency are monogenic conditions which makes them, in theory, good candidates for gene therapy. However, gene therapy efforts often require large financial investments and long timelines. As a first step, in 2019, ACD ran a fundraising campaign to fund the advancement of gene therapy for CCDS. With $50,000 raised by parents and families to be used towards gene therapy research efforts, the ACD started CCDS Gene Therapy Consortium. The mission of the consortium is to facilitate the timely sharing of information and development tools among the several labs that are pursuing gene therapies for creatine deficiencies. We believe that by building a collaborative environment and supporting through small grants shareable tools we can shorten the timeline and effort required to find gene therapy solutions for creatine deficiencies. For more updates click here.

AGAT-Inhibitors Drug Development Research Project

Principal Investigator Dr. Nicola Longo, University of Utah

The ACD is pleased to announce their support of Dr. Nicola Longo in his research into new treatments and therapies for Guanidinoacetate Methyltransferase (GAMT) Deficiency. $25,000 of the funds raised from Holiday Heroes 2020 have been dedicated to this research initiative. Presently, treatment for GAMT patients involves supplementing creatine and l-ornithine orally (between 400 and 800 mg/kg per day), an arginine-restricted diet with or without medical food, and sodium benzoate (100 mg/kg per day) to reduce the concentration of guanidinoacetate. Even with the best available therapy, the concentration of guanidinoacetate remains elevated above normal. The toxicity of guanidinoacetate is the likely cause of the incomplete response of GAMT deficiency to existing therapies and the poor response of seizures to anticonvulsivants. Dr. Longo has submitted a proposal to discover an inhibitor of the synthesis of guanidinoacetate, which would normalize the guanidinoacetate concentration in GAMT patients. These novel drugs, given with creatine supplements, should normalize the brain chemistry of GAMT patients, thus reducing the frequency of seizures and facilitating intellectual development. To learn more about this exciting research, click here or watch Dr. Longo’s presentation at the CCDS 2020 Virtual Conference.

ClinGen Collaboration

The Association for Creatine Deficiencies is working with Geisinger, a National Institutes of Health (NIH) Clinical Genome Resource (ClinGen) grantee to share genetic and health information from the ACD registry and increase our understanding of genomics. ClinGen is an NIH-funded effort dedicated to identifying clinically relevant genes and variants for use in precision medicine and research. Through their existing registry, ACD is participating in the Patient Data Sharing Program to have certified genetic counselors review and share participants’ de-identified genetic and health information. Registry participants are able to direct whether or not they would like their de-identified data shared. Data sharing can help us better understand the relationship between genetics and health, clarify uncertain genetic testing results, and provide more information about a condition to inform treatment and management. Through data sharing, individual registry participants also can choose to receive updates about their genetic testing results.

References

  • Savatt, J.M., Azzartiti, D.R, Faucett, W.A., Florin, J., Ledbetter, D.H., Miller, V.R., Palen, E., Rehm, H., Rhode,  J., Rogers, L., Talbird, S., Trutoiu, L.,  Vidal, J.A., Waggoner, C., Riggs, E.R., Martin, C.L. Expanding Patient Data Sharing: GenomeConnect’s Pilot to Engage External Registries in Data Sharing. Poster presentation. Presented at the 38th Annual Education Conference for the National Society of Genetic Counselors, November 6, 2019, Salt Lake City, Utah.
  • Savatt, J.M, Azzartiti, D.R, Faucett, W.A., Ledbetter, D.H., Miller, V.R., Palen, E., Rehm, H., Rhode, J., Rogers, L., Talbird, S., Trutoiu, L., Vidal, J.A., Riggs, E.R., Martin, C.L.  ClinGen’s Patient Data Sharing Program: Leveraging Data Sharing Experience from GenomeConnect to Broaden Patient Data Sharing Efforts. Poster Presentation. Curating the Clinical Genome Meeting. May 30, 2019. Washington, DC.

ACD Fellowships

On February 1, 2021, the ACD announced three newly established ACD Fellowships totaling $90,000 that will fund early career researchers. Dr. Charles Kuntz (in the lab of Dr. Jonathan Schlebach), Dr. Peter Axerio-Cilies (in the lab of Dr. Sylvia Stockler), and Alex Lee (in the lab of Dr. Andreas Schulze) have been selected to each receive a $30,000 ACD Fellowship Award for 2021-2022. The overarching goal of the ACD Fellowship program is to fund opportunities which have the potential for translational success. To this end, each of the awardees is focused on advancing therapeutic discoveries for creatine deficiency disorders. 

About Dr. Charles Kuntz

Charles Kuntz obtained a PhD in molecular pharmacology at Purdue University in 2015, applying computational approaches to study ligand binding mechanisms at the serotonin transporter. His work in Prof. Jonathan Schlebach’s laboratory at Indiana University focuses on molecular modeling and data science approaches utilized towards the study of the effects of mutational tolerance on membrane protein homeostasis. He will apply this experience towards identifying novel compounds that correct folding defects caused by deletion and missense mutations in the SLC6A8 gene.

 

About Schlebach Lab

The Schlebach lab was founded in 2016 at Indiana University Bloomington, and specializes in the application of emerging genetic, biochemical, and computational techniques in order to gain insights into the molecular basis of membrane protein misfolding diseases. Their lab seeks to draw from perspectives on the pharmacology of related genetic diseases in order to work towards the discovery of therapeutics for creatine transporter deficiency (CTD). With this award, Dr. Schlebach (Principle Investigator) and Dr. Kuntz (Postdoctoral Fellow) will work together to discover and validate drug candidates that correct the defects caused by a broad spectrum of CTD mutations in the SLC6A8 gene.

 

 

About Dr. Peter Axerio-Cilies

Peter received his Ph.D. in Experimental Medicine from the University of British Columbia, where he discovered and developed novel treatments for stroke and other neurological diseases. He has generated several lead drug prototypes for various protein targets associated with prostate cancer, stroke, neurological disorders, rare genetic diseases and infectious diseases. He has recently designed and implemented a drug discovery pipeline for the development of innovative neurological therapies for rare genetic diseases, including various creatine transporter (aka. SLC6a8) variants found in patients.

 

 

About Dr. Sylvia Stockler

Dr. Stockler is a Professor of Pediatrics at the Department of Pediatrics at (UBC) and head of the Division for Biochemical Genetics at BC Children’s Hospital. She authored the first description of GAMT and AGAT deficiency and has published several articles on cerebral creatine deficiency syndromes. Her research focuses on diagnosis and treatment of genetic conditions causing intellectual disability as well as on the evaluation of outcomes of treatment outcomes using innovative trial methodologies and outcome measures.

 

 

 

 

About Alex Lee

Alex Lee is a grad student in the Schulze Lab. Prior to starting his graduate studies, he completed his BSc at the University of. Toronto where he majored in neuroscience and molecular biology. His current research in the lab focuses on studying how creatine acts to regulate the expression of AGAT and the mechanism by which this occurs.

 

 

 

 

About Dr. Andreas Schulze

Dr. Andreas Schulze is a well-established Clinician Scientist who has spent the past 25+ years of medical research and clinical care in the field of Inborn Errors of MetabolismDr. Schulze leads a research group that applies biochemistry, genomics, cell biology, and model systems to improve the understanding of and develop treatments for rare inborn errors of metabolismThe main focus is on Creatine Deficiency Syndromes and Guanidinocompound-/ Arginine metabolism and Sanfilippo Syndrome