Research

ACD Research Strategy:

  • 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. Learn more on our Grants Page.
  • 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 2023 conference recordings).
  • Educate CCDS families on science and research topics relevant to CCDS (see quarterly Creatine Decoded essays and our Research Paper Repository).

Current Projects and Collaborations:

  1. Creatine Deficiency Research Center

    In the spring of 2023, with funds raised by the CCDS community, ACD launched the first ever Creatine Deficiency Research Center (CDRC) at the University of Utah. Under the mentorship of Drs. Nicola Longo and Marzia Pasquali, the first of several planned projects was launched by Dr. Steven Baker. To learn more about the Baker Lab and the research being done to find a potential therapy for Creatine Transporter Deficiency, you may view his live interview conducted Fall of 2022, his progress update shared November of 2023, or read more on Baker’s lab page (hint: be sure to click each of the tabs up top).

  2. fNIRS Biomarker Investigation Study with Boston Children’s Hospital

    The Association for Creatine Deficiencies (ACD) and Boston Children’s Hospital at Harvard Medical School have launched a collaboration to investigate the potential of functional near-infrared spectroscopy (fNIRS) technology, which has been enabled by a Ludwick Family Foundation grant. fNIRS technology will be studied to determine its potential as a non-invasive biomarker for patients affected by Creatine Transporter Deficiency (CTD) and guanidinoacetate methyltransferase (GAMT) Deficiency. This collaboration represents the first non-invasive technology to assess disease severity in those with Cerebral Creatine Deficiency Syndromes (CCDS), increasing access to medically necessary assessment tools for children with disabilities. 

    ACD will host the “International Creatine Deficiency Day” at Boston Children’s to hear from experts in this field and officially open the study. This will be a hybrid event for both in-person and virtual (Zoom) attendees. It takes place on February 1, 2024, 12pm-4pm Eastern.

    Click here to register for International Creatine Deficiency Day.

    Further collaboration among medical professionals and researchers will happen at the 2024 CCDS Scientific + Patient Symposium in Salt Lake City, Utah, as well as the second phase of testing which will open up the trial to a larger percentage of CCDS patients. 

    To read more, please view the News Release. If you would like to register for the fNIRS testing, please fill out this form.

  3. Core Outcome Set Workshop & Summary Report

    The CTD and GAMT deficiency Core Outcome Set (COS) study involved an evidence study, the globally distributed Delphi study, and the consensus workshop meeting. The core outcomes narrowed from 50 potential outcomes after the evidence study to 20 potential outcomes after the Delphi study, based on parent, caregiver and medical professionals responses. The consensus workshop allowed the attending parents, caregivers, and medical professionals to narrow it further to the final set of 8 core outcomes. A manuscript of the 8 core outcomes is being drafted and a final report will be published in a peer-reviewed journal. 

  4. ClinGen Collaborations

    The Clinical Genome Resource (ClinGen) is an effort funded by the National Institutes of Health (USA) dedicated to determining the clinical relevance of genes and variants for use in precision medicine and research.

  5. ClinGen’s Genome Connect

    The Association for Creatine Deficiencies is working with Geisinger, a ClinGen grantee to share genetic and health information from the ACD registry and increase our understanding of genomics. 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.

  6. ClinGen CCDS Variant Curation Expert Panel

    Understanding the clinical significance of genetic variants is important to the integration of genomic medicine in healthcare. ClinGen has assembled a group of experts to generate gene-specific guidelines to determine the clinical significance of variants in the genes involved in CCDS. This group, called the ClinGen CCDS Variant Curation Expert Panel (VCEP), uses their guidelines to classify variants in each of the three CCDS genes and then submits the classifications and supporting data to publicly available variant databases, including ClinVar and the ClinGen Evidence Repository. The Food and Drug Administration (USA) approved ClinGen’s VCEP process in December 2018. In order facilitate variant classification by the ClinGen CCDS VCEP, the ACD may share de-identified genetic and phenotypic data with the group. This increased understanding of genetic variants expedites the molecular diagnosis of CCDS, thereby supporting early clinical intervention and development of targeted therapies.

  7. 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.

Past Projects

  1. ACD 2022 Fellowships

    Dr. Charles Kuntz in the lab of Dr. Jonathan Schlebach and Dr. Peter Axerio-Cilies in the lab of Dr. Sylvia Stockler
    Dr. Kuntz and Dr. Schlebach will work with Dr. Axerio-Cilies and Dr. Stockler to identify drugs that may rescue creatine uptake across different types of SLC658 mutations. These fellowship projects compliment each other in characterizing specific mutations and how they respond both in computer simulations and petri dish experiments to existing compounds.

    Through these studies, they are identifying potential treatments targeting specific genetic variants by identifying drugs that can be repurposed and can restore functional activity (creatine uptake) of the dysfunctional SLC6A8 transporters. Results from the first year of these studies showed that there are existing compounds that may increase creatine transport in non-functional mutations.

    Léa Broca-Brisson in collaboration with Dr. Aloise Mabondzo
    Léa Broca-Brisson is focused on development of human brain organoids from CTD patients as a tool for evaluating the efficacy of potential treatments. She plans to identify biomarkers as a standard for measuring treatment success, particularly in relation to cognitive improvements.

    Alex Lee in the lab of Dr. Andreas Schulze
    Alex Lee intends to continue his work on understanding regulatory mechanisms for genes critical to the creatine synthesis and transport pathway.

  2. 2021-2022 AXXAM Project

    Project Title: A high throughput screening assay for CTD drug discovery.

    Learn more by watching the AXXAM Presentation at the 2022 CCDS Scientific and Patient Symposium here.

  3. ACD 2021 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 Metabolism. Dr. 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 metabolism. The main focus is on Creatine Deficiency Syndromes and Guanidinocompound- Arginine metabolism and Sanfilippo Syndrome.

  4. 2021 AGAT-Inhibitors Drug Development Research Project

    Principal Investigator Dr. Nicola Longo, University of Utah

    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 research, click here or watch Dr. Longo’s presentation at the CCDS 2023 Virtual Conference.