This page features CCDS research posters presented at various conferences.
If you presented a poster on a Cerebral Creatine Deficiency Syndrome and would like it listed here, email us at research@creatineinfo.org with the poster file attached and the author name(s), conference it was presented at, month and year presented, and any additional details or questions.
SHORT SUMMARY
SLC6A8 creatine transporter deficiency has no effective treatments and continues to impact patients and their families. We are working to develop new models to study the intricacies of this disorder including 3D “mini brains” (organoids) and neurons with the goal of testing a corrective gene therapy. Preliminary results indicate that a virus carrying a promoter that is expressed in every cell has a higher creatine uptake compared to a neuron specific promoter. Additionally, SLC6A8 patients had organoids that grew to a larger size, suggesting a more immature developmental state. We will continue testing our gene therapy and culture systems to further understand this disorder.
ABSTRACT
The discovery of the first mutation in the SLC6A8 creatine transporter gene marked a significant advancement in understanding the pathophysiology of X-linked neuronal impairments with an unknown etiology. The absence of functional SLC6A8 creatine transporters results in inadequate uptake of the high-energy metabolite creatine into the brain, causing a spectrum of neurodevelopmental delays including intellectual disability, epilepsy, and behavioral disorders. Conventional therapeutic approaches, such as oral creatine supplementation, are ineffective due to the inability of patients with SLC6A8 mutation to facilitate cerebral creatine transport, leaving a significant therapeutic void and lack of symptom relief. Furthermore, there is a significant lack of knowledge regarding the cerebral development of individuals afflicted with SLC6A8 creatine transporter deficiency. Our research aims to address this gap by examining the developmental processes underlying SLC6A8 mutations using cerebral organoids and evaluating a range of adeno-associated virus (AAV)-mediated therapeutic interventions aimed at increasing cerebral creatine levels. Preliminary findings from our laboratory reveal a notable acceleration in the growth rate of cerebral organoids from individuals with SLC6A8 mutations compared to CRISPR-corrected isogenic controls. Subsequent investigations into AAV vectors will extend these observations to murine models and continue to explore organoid models through comprehensive transcriptome analyses, RNA sequencing, and advanced electrophysiological assessments. Through our multidisciplinary approach encompassing stem cell biology, gene therapy, and neurodevelopmental research, we aim to bridge the therapeutic gap and advance treatment paradigms for individuals affected by SLC6A8 creatine transporter deficiency.
SHORT SUMMARY
Alex Edwin presented ongoing research from the Montine Lab at Stanford Medicine. Their work aims to develop an orally bioavailable small molecule therapeutic for Creatine Transporter Deficiency. This poster summarizes the progress that has been made in the first six months of their project.
ABSTRACT
Effective delivery of creatine or a creatine mimetic has been the goal of numerous therapeutic approaches for the treatment of Creatine Transporter Deficiency. To date, the most advanced approaches utilize ester and amide prodrug linkages for delivery of creatine across the blood brain barrier and neuronal membranes. As a result of this work, fatty acid amide hydrolase (FAAH) has been identified as a potential enzymatic target for the controlled release of creatine within neurons. FAAH is highly expressed in brain tissue and has a broad specificity for various fatty acid amide compounds. However, prodrugs that currently target FAAH tend to suffer from poor metabolic stability and low solubility, reducing their bioavailability. To address these issues, our research focuses on refining current prodrug delivery methods. We have developed two assays for the measurement of creatine release from prodrugs in human HAP1 CrT KO cell cultures and mouse CrT KO hippocampal slice cultures. With these assays, our ongoing research seeks to identify a novel orally administered creatine therapeutic which has enhanced solubility and bioavailability within the CNS.
SHORT SUMMARY
ABSTRACT
Creatine Transporter Deficiency (CTD) is a rare genetic disorder related to SLC6A8 pathogenic variants, leading to moderate to severe intellectual disability. Little is known about the cardiac consequences of the disease. A model of CTD in mice suggested a risk of sudden cardiac death. Long QTc interval, frequent premature ventricular contractions (PVCs) and left ventricular dilatation (LVD) were reported in some CTD patients. In order to determine the cardiac CTD patient phenotype, we performed a prospective study on 24 French male CTD patient including resting 12-lead ECG, 24-hour ambulatory ECG and transthoracic echocardiography (TTE). We present here preliminary results on the first 17 CTD patients included (mean age 17.5 ± 4.2 years). 24-hour ambulatory ECG was impossible in 2 patients. No patient had syncope. No patient had LVD, or LV systolic dysfunction. LV posterior wall thinning was observed in only one patient. On resting 12-lead ECG, prominent U-waves were common (80%) and the QTc was of normal duration in all patients when U-waves were excluded (429.5 ± 21.5 ms). 24-hour ambulatory ECG revealed an abnormal intermittent ECG pattern, associating paroxysmal prominent U-waves (100%) and paroxysmal biphasic T-waves ( 93.3 %). PVCs were rare (30.1 ± 79.2 per 24h). Contrary to what was suggested in the literature, we did not find any long QTc interval (after exclusion of U-waves) or LVD. We documented abnormal ventricular repolarization pattern with prominent U-waves and biphasic T-waves. Cardiac follow-up is needed.
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SHORT SUMMARY
ABSTRACT
Over 100 loss-of-function (LOF) mutations within the SLC6A8 creatine transporter (CT1) are known to cause creatine transporter deficiency (CTD) syndrome. Most of these mutations enhance CT1 misfolding and degradation, and the resulting loss of the transporter protein ultimately compromises creatine uptake within the brain and other organs. Creatine uptake could therefore be restored by small molecule “correctors” that rescue the expression of misfolded variants, the development of which has recently revolutionized the treatment of several other genetic diseases of membrane protein misfolding. Cumulative observations concerning the mechanistic effects of drugs targeting related SLC6 transporters such as the serotonin (SERT) and dopamine (DAT) transporters suggest compounds that selectively bind to their inward-facing (IF) conformation generally enhance their expression and maturation. Based on these considerations, we set out to identify small molecules that selectively bind to the IF conformation of CT1 in order to restore the expression and activity of misfolded CT1 variants. Towards this goal, we developed a virtual screening approach to identify small molecules that selectively bind to the IF conformation of CT1, then profiled their effects on CT1 expression. Of our top 53 candidates, we identify several that alter the expression profile of WT CT1 and a few that enhance its expression at the plasma membrane. We are currently working to determine how these molecules impact CT1 function and how they impact pathogenic CT1 variants. Additionally, based on the structures of our top hits, we are currently searching for second-generation compounds with increased potency. These results represent an important step toward the development of novel pharmacological chaperones for the treatment of CTD.
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SHORT SUMMARY
A summary of highlights from the Voice of the Patient Report (VOP). The VOP is a written account of the January 2023 EL-PFDD Meeting, polls conducted, and comments submitted by those in attendance.
ABSTRACT
Externally-Led Patient Focused Drug Development (ELPFDD) meetings are a methodical way to make sure that patient and caregiver perspectives related to living with a disease are considered throughout the drug development process. In addition to patients and caregivers, these meetings are attended by regulatory agencies, industry, researchers, and clinicians. Following the ELPFDD, an extensive Voice of the Patient (VOP) report is compiled, capturing all of the data and a summary of the information shared throughout the meeting. This report is submitted to the FDA, to be used as a reference point when drugs or therapies are reviewed. The Association for Creatine Deficiencies (ACD) hosted a virtual ELPFDD meeting in January 2023 on Cerebral Creatine Deficiency Syndromes (CCDS). Following a brief introduction with remarks from the FDA and a clinical overview of CCDS, the meeting was divided into two main sessions – one focusing on living with CCDS and the other focusing on current and future approaches to treatment for CCDS. The CCDS VOP is a comprehensive summary from the meeting. It includes key insights, a wealth of data, and impactful quotes from patients and caregivers throughout. This poster aims to provide a visual summary of the CCDS VOP.
SHORT SUMMARY
Dr. Filippo Ingoglia presented this poster at the 2024 CCDS Patient + Scientific Symposium, in Salt Lake City, Utah. The poster describes the development of a functional assay to diagnose creatine transporter deficiency using UPLC-MSMS system. The assay will allow for the confirmation of the diagnosis of CTD and possibly the identification of CTD patients with residual transport activity. The project was funded by ACD.
ABSTRACT
Creatine transporter deficiency (CTD) is an X-linked disorder caused by variants in the creatine transporter gene (SLC6A8) and characterized by intellectual disability, failure to thrive, speech delay, autistic-like behavior, and seizures. Affected patients have increased urine creatine/creatinine ratio and pathogenic variants in the SLC6A8 gene. Genetic testing can miss variants outside the coding region of the gene or detect missense variants of uncertain significance (VUSs). In such cases, a functional assay can be used to confirm the diagnosis. We are developing a new assay to measure creatine transport in fibroblasts using a stable isotope rather than radioactive creatine. Uptake in cells from patients with suspected creatine transporter deficiency will be compared to those of normal cells and cells with known pathogenic variants in the SLC6A8 gene. In addition, we will immortalize fibroblasts hemizygous for a null allele and express in them the normal SLC6A8 minigene and one in which VUS have been recreated. This assay will confirm the diagnosis of creatine transporter deficiency, determine whether there is residual creatine transport activity, and define the function of VUS without the need for a skin biopsy in each patient.
SHORT SUMMARY
In this study, we used wild-type and GAMT knockout mice to study how treating them with creatine affected the levels of creatine and guanidinoacetate within their organs as well as how this treatment affects AGAT expression. We observed that the knockout mice that were given creatine had increased levels of creatine in all organs and reduced levels of guanidinoacetate in all organs except the liver. Furthermore, treating the GAMT knockout mice with creatine resulted in significant reductions in AGAT protein levels and activity. Our research confirms that creatine administration lowers guanidinoacetate in GAMT deficiency via reduced AGAT expression.
ABSTRACT
We carried a multidimensional study to examine the effect of creatine supplementation on arginine-derived guanidino compounds, AGAT expression and AGAT activity in creatine-deficient mouse model. Adult wildtype, heterozygous and GAMT-deficient mice were kept either on creatine-free, 2% or 4% creatine supplemented mouse chow for 10 weeks. Mouse urine and blood were collected at the beginning and the end of the trial; mouse tissues were harvested at the end of the study. An appropriate age matching non-treatment mouse group was used as a control for tissue analysis. In urine, plasma and selected tissues LCMSMS analysis demonstrated varied effect of creatine supplementation on creatine and guanidino acetate (GAA) levels. Wildtype mice showed increase of creatine in urine, plasma, kidneys and liver and there was no change in brain, heart and muscle. Mutant mice on the other hand showed increase of creatine in urine, plasma and all organs. Further, creatine supplementation led to decrease of GAA in urine, plasma and all organs of wildtype mice. Mutant mice also showed reduction of GAA in their organs, except liver. Western blot analysis revealed marked decrease in AGAT gene expression in kidneys, brain and liver following creatine supplementation. Since the creatine effect on AGAT mRNA in liver was inconclusive, we measured AGAT enzyme activity and could confirm reduced AGAT activity. In conclusion, we can demonstrate the efficacy of creatine on reduction of GAA in mice. The mechanism by which creatine reduces GAA is the noticeable inhibitory effect of creatine on AGAT expression.
SHORT SUMMARY
In this study, our goal was to investigate how high levels of creatine are able to cause reductions in AGAT expression. Through the use of various reporter constructs, we were able to identify a 23 amino acid sequence within the AGAT protein that plays a key role in allowing it to respond to creatine. When this 23 amino acid sequence is fused to other proteins, high levels of creatine are able to decrease this protein’s expression. With this result, we hypothesize that creatine is able to regulate AGAT expression by interfering with the activity of ribosomes which is the cellular machinery responsible for protein production.
ABSTRACT
Arginine:glycine amidinotransferase (AGAT) is the rate-limiting enzyme in the twostep biosynthetic pathway of creatine (CT). Increasing intracellular levels of CT results in decreased AGAT mRNA, protein expression, and enzyme activity. In previously described experiments, we have used genome editing to produce a HAP1 cell line that expresses a C-terminal tagged AGAT-NanoLuc Luciferase (AGAT-NLuc) reporter to monitor the decrease in AGAT expression with increasing intracellular CT. Co-treatment with CT and a transcriptional inhibitor, Actinomycin D, or a translation inhibitor, cycloheximide, suggested the involvement of a post-transcriptional mechanism controlling in AGAT expression. We have identified a 23 amino acid long sequence on the N-terminus of AGAT (‘AGAT peptide’) that enables the CT responsiveness. Fusing this sequence in-frame or as an upstream open reading frame to Firefly Luciferase and expression in cells results in a dose-dependent decrease in luminescence with increasing CT. We hypothesize that the mechanism by which CT controls AGAT expression involves ribosomal stalling. During translation, CT could interact with the nascent AGAT peptide arresting further AGAT translation and reducing AGAT mRNA stability. We have generated a series translation-arrest reporters consisting of a Nterminal Nanoluc Luciferase and C-terminal Firefly luciferase with InterVening Sequences consisting of Internal Ribosome Entry Sites and/or P2A Translation Reinitiation Sequences along with the wild type or mutated AGAT peptide. Our results are highly suggestive of the AGAT nascent N-terminal amino acid sequence acting as a translation arrest peptide.
This poster is not available; Research remains in progress
SHORT SUMMARY
This work presents a promising approach for future CTD treatment. The nanoparticles we designed, composed of safe materials commonly used in the food industry, and have successfully delivered creatine to CTD-patient cells in a cell culture model. While we still have a lot of work to do, the particles helped CTD-patient cells survive prolonged starvation, demonstrating that our technology can penetrate cells and improve outcomes.
ABSTRACT
Creatine Transporter Deficiency (CTD) is an X-linked disorder characterized by a dysfunctional Creatine Transporter (CrT), leading to impaired creatine uptake and disrupted cerebral energy metabolism. Despite the critical role of creatine in cellular energy balance, effective treatments for CTD are currently lacking. Novel therapeutic approaches, such as gene therapy or nanoscale delivery systems, hold promise for addressing this unmet medical need. In this study, we report the synthesis and characterization of novel creatine-loaded, polyphenol-based particles. Our particles exhibit an impressive loading capacity exceeding 50% and demonstrate no discernible toxicity towards mature hiPSC cortical neurons. Comprehensive characterization employing LC-MS, FTIR, UV-visible spectroscopy, fluorescence spectrophotometry, and Dynamic Light Scattering highlights the distinctive properties of this innovative formulation, laying a solid foundation for its further advancement. FTIR spectroscopy analysis reveals no alterations to creatine, suggesting its loading mechanism relies on Van der Waals forces rather than permanent chemical conjugation. Additionally, fluorescence spectrophotometry indicates a close interaction between creatine and the phenolic compound utilized in the synthesis. Importantly, the synthesized particles are composed of Generally Regarded as Safe (GRAS) materials, ensuring their safety for biomedical applications, and have an average hydrodynamic radius of 318 nm, a zeta-potential of -18 mV, and a polydispersity index of 0.22.
SHORT SUMMARY
This poster provides an overview of the Core Outcome Set for GAMT & CTD- its purpose, how the COS was developed, and the final 8 outcomes included.
ABSTRACT
Clinical trials aim to determine the safety and effectiveness of interventions by evaluating their impact on diverse endpoints. However, inconsistencies in defining and measuring these endpoints have posed challenges in applying and comparing trial results. A list of important outcomes, called a core outcome set (COS), is developed to identify a small set of disease-specific outcomes deemed important by stakeholders, and should be reported in every research study and clinical trial. Unfortunately, patient and caregiver perspectives have historically been overlooked in the COS development process, thus limiting their input into the outcome selection. ACD collaborated with caregivers and health professionals to develop a COS of eight outcomes for creatine transporter deficiency (CTD) and guanidinoacetate methyltransferase (GAMT) deficiency. Caregivers were partners throughout the COS development process, increasing community engagement and facilitating caregiver empowerment. Here, we provide an overview of our entire COS development project. Our multifaceted approach included (1) conducting evidence reviews (i.e., focus groups, literature reviews, patient registry data), (2) developing three Delphi surveys for input from the CCDS community at large, and (3) hosting a consensus workshop with caregivers and health professionals to finalize the COS. We expect that this project will (1) ensure a patientcentered approach for accelerating drug development, (2) minimize bias, and (3) promote a more efficient use of resources.
SHORT SUMMARY
This poster summarizes findings from the CreatineInfo Natural History Study and Patient Registry’s cardiovascular survey.
ABSTRACT
Prior research has demonstrated that patients with creatine transporter deficiency (CTD) are at greater risk for developing a cardiovascular condition called prolonged QTc, which is an irregular heart rhythm. Although prior research has been conducted to understand the relationship between CTD and cardiovascular health, little research has been conducted to determine whether or not there is a relationship between arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltransferase (GAMT) deficiencies and cardiovascular health. Therefore, the goal of this project was to better understand the relationship between all three cerebral creatine deficiency syndromes (CCDS) and cardiovascular health using patient- and caregiver-reported data. We developed a cardiovascular health survey which was launched via the CreatineInfo Patient Registry. Survey questions included topics such as the CCDS patient’s cardiovascular health history, cardiovascular testing, exercise habits, and family cardiovascular history. This survey was the first to capture cardiovascular health data within our CreatineInfo patient registry. Our preliminary findings show that CTD patients report experiencing cardiovascular conditions, unlike GAMT and AGAT deficiency patients. Additional research is needed to fully understand the long-term impacts on cardiovascular health among CCDS patients.
SHORT SUMMARY
This poster provides an overview of an ACD collaboration with an industry partner to better understand CTD patient oral medication preferences- both the process of partnering as well as the results of the survey.
ABSTRACT
Background: An Association for Creatine Deficiency (ACD) industry partner developing a possible treatment for creatine transporter deficiency (CTD) approached ACD to develop a custom patient registry survey to learn about oral medication preferences to inform the development of their therapeutic.
Methods: 1. Created a data sharing agreement to establish protections for both ACD and the industry partner, and define project services, deadlines, deliverables, and payment schedule. 2. Drafted a survey in collaboration with the industry partner. 3. Consulted with a metabolic dietician to provide guidance on the proposed questions. 4. Gathered feedback from ACD’s Family Advisory Board (FAB). Feedback from the FAB ensured patient and caregiver perspectives were represented in the survey questions and the language was participant-friendly. 5. Developed a recruitment campaign to promote community engagement with the survey
Results: 1. An industry and non-profit data sharing agreement appropriate for future use. 2. A custom oral medication survey. 3. A successful recruitment campaign with high participant engagement surpassing our target goal, with 37 CTD participants completing the survey in the first six weeks. 4. A final data report containing aggregate, de-identified results from the survey. 5. Insights into patient oral medication preferences appropriate for sharing with stakeholders in future drug development efforts. 6. Industry partner support of registry costs resulting in a self-sustaining registry
Conclusions: Development of a custom registry survey can mutually benefit patient advocacy groups and industry partners. ACD observed that survey participants were incentivized to complete the survey by simply knowing that their data had meaningful implications, setting the foundation for future successful survey recruitment strategies.
SHORT SUMMARY
This poster highlights the benefits of early diagnosis of GAMT by comparing outcomes for GAMT sibling pairs- one of which was diagnosed at a younger age, and the other at an older age.
ABSTRACT
Background: Singular observations in GAMT deficiency, an ultra-rare, severe neurodevelopmental disorder, imply the benefit of early, presymptomatic treatment.
Methods: Four GAMT- and 8 age-matched control sibling pairs were enrolled. Based on structured interviews with 4 GAMT families a Redcap questionnaire was constructed. For example, parents were asked to indicate whether and when their child achieved specific milestones, achieved them with support, or did not achieve them. Questions included developmental milestones, fine motor-, cognitive-, self-care-, and social skills, behavior, coordination, and therapy/support.
Results: GAMT sibling pairs were diagnosed at 0.0/5.6, 0.0/0.8, 1.1/5.8, and 3.8/8.8 y (younger/older), with current age of 11. 4/16.8 y (9.0-13.6/14.0-18.7) (mean (range), younger/older). The healthy controls were 9.9/13.5 y (4.9-12.0/8.8-16.0). In interviews, the parents identified intellectual level, communication, and self-care skills as the major difference between their two children with GAMT. Using the questionnaire responses, we compared the older child with its younger sibling in each pair. In GAMT, the comparison revealed consistent and distinct differences in every tested domain with the younger sibling performing better than its older sibling. There was no such difference in control sibling pairs. We further assessed GAMT outcome of early treatment (initiated <13 months, n=4) vs late treatment (initiated >3 years, n=4). There was normal to almost normal outcome in the early treatment group, while all children with late treatment demonstrated mostly large deficits in all investigated domains. Conclusion: This study convincingly confirms the notion that early initiation of treatment results in much improved outcomes in children with GAMT deficiency. Early identification of affected individuals required for timely treatment, ideally in the presymptomatic phase of the disease, makes universal newborn screening for GAMT mandatory.
*This poster was also presented at the 2024 Curating the Clinical Genome Conference by Jenny Goldstein.
SHORT SUMMARY
ClinGen’s Cereberal Creatine Deficiency Syndromes Variant Curation Expert Panel (CCDS VCEP) has been diligently working to classify variants in the three CCDS associated genes, GATM, GAMT, and SLC6A8 for upload into the publicly available database ClinVar. In collaboration with the Association for Creatine Deficiencies (ACD) and CreatineINFO, the CCDS VCEP has requested de-identified biochemical and genetic data on some CCDS variants, which has enabled the reclassification of 50% (n=3) variants, two of which were reclassified from a Variant of Uncertain Significance to Likely Pathogenic, and one reclassified from Likely Pathogenic to Pathogenic. Ongoing collaboration between the ACD, CreatineINFO, and the CCDS VCEP is critical for accurate variant interpretation for families as well as the genetic community and serves as a model for other organizations to further the goal of improving patient care through genomic medicine.
ABSTRACT
Background/Objectives: Understanding the clinical significance of variants within the genes causing cerebral creatine deficiency syndromes (CCDS) is important to ensure timely diagnosis and initiation of treatment for these neurological disorders. The Association for Creatine Deficiencies (ACD), a patient advocacy organization, collaborates with the NIHfunded Clinical Genome resource (ClinGen) to share data and assist in robust variant classification.
Methods: Via collaboration with ClinGen’s GenomeConnect, ACD registry participants provide their genetic testing reports for submission to the public variant database, ClinVar. Data is also shared with the ClinGen CCDS Variant Curation Expert Panel (VCEP), which has developed guidelines for classification of variants in the genes causing CCDS (GAMT, GATM, SLC6A8) and submits those classifications to ClinVar as part of an FDA-approved process. Results: Using published data, the ClinGen CCDS VCEP has classified 43 variants from ACD registry participants; 15 were classified by the VCEP as pathogenic (8 SLC6A8, 7 GAMT), 7 likely pathogenic (LP) (5 SLC6A8, 2 GAMT), 2 benign (1 SLC6A8, 1 GAMT), and 19 were variants of uncertain significance (VUS) (15 SLC6A8, 4 GAMT). 12 VUS were identified as tending towards LP by the VCEP based on the strength of evidence already available; ACD participants with these variants were recontacted to request additional case-level data (biochemical testing, magnetic resonance spectroscopy, family history, genetic testing of parents) with the goal of reclassifying these variants as LP or pathogenic.
Conclusions: Collaboration between the ACD and ClinGen increases understanding of the clinical significance of variants in the gene causing CCDS and may serve as a model for collaboration between other ClinGen VCEPs and patient advocacy organizations.
SHORT SUMMARY
ABSTRACT
Rationale: There is currently no treatment for SLC6A8/CRT-1 related intellectual disability. We have established a 3- tier pipeline to find repurpose-able drugs for this condition.
Methods:
Tier 1: In silico drug screening using a library of FDA approved drugs to identify drugs that would bind to the high-resolution 3D structure of SLC6A8/CRT-1 protein.
Tier 2: In vitro testing of candidate drugs for their ability to rescue mutant SLC6A8/CRT-1 activity using electrophysiological patch clamp technique and measuring changes in transmembrane sodium gradient in SLC6A8 variant transfected HEK293 cells.
Tier 3: To further validate tier 2 results, creatine uptake studies are performed in SLC6A8 deficient human fibroblasts measuring cellular uptake of D3 labelled creatine (D3-creatine) and its intracellular conversion to phosphocreatine (D3-PCr). Guanidino-propionate (GPA), a competitive inhibitor of SLC6A8-mediated creatine uptake is used to confirm SLC6A8 specificity of the measured uptake rates.
Results: Using Tier 1 and 2 we have identified 12 candidate drugs / compounds which partially rescue deficient SLC6A8 activity in transfected HEK293 cells. 6/12 compounds can potentially be used for off label prescription in n-of-1 studies. 5/6 are effective in variant Phe408del and Asn336del. One compound (4PBA) showed efficacy in several SLC6A8/CRT-1 missense mutations. We have created data for time and dose dependent D3-creatine uptake in wild type and Phe408del fibroblasts informing experimental protocols for further drug testing. Work in progress: To test D3-creatine uptake in Phe408del fibroblasts (purchased from the Coriell Biobank) and in Asn336del fibroblasts (once available) in response to 5 repurpose-able drugs identified in tier 2.
Acknowledgement: Our research is generously supported by the ACD.
