Grants Awarded

Grant Awarded July 2020 by the Cystinosis Research Network and Cystinosis Ireland

A Cellular Resource for Studying Male Infertility in Cystinosis, Minnie Sarwal, MD, PhD, Professor of Surgery, (Director, Precision Transplant Medicine) University of California San Francisco (UCSF), James Smith, MD, MS (Director, Male Reproductive Health Center Urologist), University of California San Francisco (UCSF), Ann Harris, Professor, Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, Elena Levchenko, Professor, Department of Pediatric Nephrology, Leuven, EU, and Swastika Sur, MSc., PhD Postdoctoral Scholar, Sarwal Lab, University of California San Francisco, Department of Surgery.

Total Grant: €10,000

Principal Investigator, Swastika Sur, a Postdoctoral Fellow at the University of California San Francisco, has outlined a research proposal focused on infertility in men with cystinosis.

In addition to various endocrine organs that are affected in cystinosis, hypergonadotropic hypogonadism has been reported as a frequent finding in male cystinosis patients. Although spermatogenesis has shown to be intact at the testicular level in some patients, no male cystinosis patient is known to have naturally fathered a child. The sole treatment for cystinosis is the aminothiol cysteamine, which is highly effective in reducing the intracellular levels of cystine. However, this drug is ineffective in the treatment of male infertility in these patients.

A previous study of the pathophysiology of cystinosis-mediated infertility used a CTNS-/- mouse model. However, the CTNS-/- mouse model generated on C57BL/6 background was found to not be suitable for clarifying the pathogenesis of male infertility in cystinosis. This mouse model partially mimics the renal phenotype of the human disease but was found to have normal testicular morphology and function.

Therefore to this date, the exact pathophysiology of male infertility observed in patients with cystinosis is not yet fully understood, which is a critical unmet need due to the growing population of cystinosis patients, treated with cysteamine reaching young adulthood.

This project proposes to generate isogenic immortalized epididymis and testicular cell models to study infertility associated with cystinosis, by using CRISPR/Cas9 technology to develop a deletion in the CTNS gene of normal human epididymis and testicular cells. The Sarwal group’s ongoing collaborations with Dr Smith at UCSF has enabled access to a rich tissue resource of normal testicular and epidydymal samples that will be used for generating this cystinosis- specific resource. The Sarwal research group also has ethical approvals in place at UCSF and at KU Leuven that will allow Dr Sur to approach cystinotic patients for access to patient biosamples.

Previously, the Sarwal research group successfully generated human immortalized CTNS-/- proximal tubular epithelial cells, and confirmed the phenotype of these newly developed cell line in terms of intracellular cystine levels by HPLC-MS/MS.

In this project, Dr Sur will focus on generating human immortalized CTNS-/- epididymal and testicular cells, followed by phenotype validation so that these cell lines can serve as a resource for the research community to study the pathophysiology of male infertility observed in cystinosis.

The Specific Aims of this project are the following:

• Aim 1: Generate human immortalized CTNS -/- epididymal and testis cell lines by CRISPR/Cas9 and confirm the phenotype to further downstream study of male fertility associated with cystinosis
• Aim 2: Map the molecular perturbations in both cell lines with deletion of CTNS and in tissue samples from male cystinotic patients, by using state of the art genomics that the Sarwal Lab has legacy expertise-in. This will define the clinical utility of the resource generated in Aim 1.

This project will provide a first of its kind human cellular models to study cystinosis-mediated male infertility.

CRN Research Funding Update Q4 2018

Grant Awarded October 2018

Study of Neuronal Structure and Function Changes in Cystinosis, John Foxe, PhD and Krishnan Padmanabhan, PhD

Department of Neuroscience Ernst J. Del Monte Institute for Neuromedicine, University of Rochester School of Medicine and Dentistry, Rochester, NY

Year One: $110,000 Total Grant: $110,000

Investigators at the Department of Neuroscience Ernst J. Del Monte Institute for Neuromedicine, University of Rochester School of Medicine and Dentistry Rochester, NY have outlined a research proposal taking a novel systems neuroscience strategy to address the link between molecular/cellular pathology of the lysosomal system in neurons and the resultant changes in the structure and function of neuronal circuits using new electrophysiology, imaging and computational methods to understand the effect of cystinosis on neural circuits. By identifying the mechanisms underlying the neuropathology of the disease at the basic science level, this research program will provide important biomarkers for tracking disease progression, could identify new sites/targets for intervention and guide in the development of strategies for treatment. Following is a brief update on their project: The aim of our research study is to understand how changes at the level of cells in the brain due to lysosomal storage dysfunction translate to changes in cognitive function and behavior. To study the neurobiological underpinnings of cystinosis, the lab uses a Ctns -/- mouse line which has a cystinosis, nephropathic, targeted mutation 1 in the gene. To do this, we have developed new technologies from recording the electrical activity of the brain in this model. Specifically, we have deployed a method for studying the physiology of individual neurons throughout the brain in awake behaving animals. This cutting edge research approach will allow us to identify the neurophysiological changes that arise from the Ctns -/- mouse and relate this to alterations in global brain dynamics. The ultimate goal being to discovery biomarkers of the disease and identify potential targets for subsequent intervention. In the first 6 months of this research project, we have successfully recruited and trained an MD/PhD student with interests in Neurology and development to perform surgeries and record from control mice to characterize baseline patterns of activity throughout the brain for comparison with the Ctns -/- mouse.

Altered protein kinase signaling as a cause of reduced adhesion and increased motility of renal epithelial cells in Cystinosis – E. Ivanova, L. van den Heuvel, E Levtchenko (Principal Investigator) Katholieke Universiteit Leuven, Belgium

Year Two: $88,493 Total Grant: $165,494

Cystinosis is a genetic disease manifesting early in life (≈ 6-12 months) with progressive kidney disease resulting in renal failure early during childhood if not treated. In cystinosis the metabolism of the amino acid cystine is defective leading to its accumulation in the kidney and other organs. This cystine accumulation results in cellular damage and death, but the direct mechanisms beyond this phenomenon are largely unknown. Some harmful cellular events in cystinosis might not be directly related to cystine accumulation and are the subject of our research project. Based on our previous work we hypothesized that the loss of highly specified renal cells like glomerular podocytes and renal proximal tubular cells in urine is a major mechanism causing renal pathology of cystinosis. Increased rate of cellular abundance in urine can be explained by either the decreased adhesion of renal cells to their matrix or their increased motility or by a combination of both mechanisms. Indeed we demonstrated that both events occur in cultured human renal cells derived from cystinosis patients. We further tried to explore the mechanisms beyond this cellular loss. It has been reported in other diseases that increased cell motility and defective adhesion can be associated with the altered protein kinase signaling. In cystinotic podocytes we found an increased expression of activated or phosphorylated Akt kinases compared to control cells. This could explain, at least partially, the abnormal phenotype. We are currently testing other protein kinases that might contribute to this mechanism. In addition we tested the gene expression of several integrin in podocytes, as podocytes adhere to the extracellular matrix using integrin receptors. Although only minor differences were found between cystinotic and control cells, cell surface expression of these proteins still has to be studied. So far most of our experiments were done in podocytes. We recently started to investigate proximal tubular epithelial cells which also showed an increased expression of phosphorylated Akt kinases unifying the concept of the hypothesis over different renal cell types. Our future plan includes also the experimentation with different kinase inhibitors to explore if they can reverse abnormal renal phenotype.

Mechanisms Underlying Neurocognitive Changes in Cystinosis, John Foxe, PhD Co‐Principal Investigator, Sophie Molholm, PhD Co‐Principal Investigator, Steven U. Walkley, DVM, PhD Co‐Principal Investigator Departments of Neuroscience and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY

Year three: $100,980 Total Grant: $467,950

Travel Addendum: $38,352

The goal of this proposal continues to focus on brain-related changes in the lysosomal disease, cystinosis, through the use of complementary state-of-the-art neurocognitive studies (in cystinosis patients, Aim 1), cell biological analyses and possible treatment strategies (in the mouse model, Aims 2-3). Progress through year 02 of the proposal are outlined below.

AIM 1: To explore sensory processing and multisensory integration as potential biomarkers using high-density electrophysiological mapping techniques in individuals with cystinosis.

This section of the report details progress in the human arm of the CRN project entitled – “Mechanisms Underlying Neurocognitive Changes in Cystinosis”. Under this arm of the project, our main aim was to “explore sensory processing and multisensory integration as potential biomarkers using high-density electrophysiological mapping techniques in individuals with Cystinosis”. Therefore, initially, we recorded high-quality data from 7 patients with Cystinosis while they responded to a sensory processing task. We performed preliminary analyses of those data, compared the outcomes to similar recordings in another lysosomal disorder (Niemann-Pick-C (NPC); N=17) and to an already collected extensive normative dataset recorded from a cohort of matched neurotypical control participants (N=84). The most surprising aspect of those results was the strikingly “normal” patterns of multisensory behavior and neurophysiological responses that we obtained in Cystinosis, in stark contrast to those obtained in the NPC population. As a consequence of this finding, we decided to apply additional paradigms that tap into sensory processing and executive functions, which, based on the clinical phenotype of individuals with Cystinosis, are likely to provide sensitive brain measures of neural function/dysfunction in the Cystinosis population. In this second phase, we have collected data from 32 patients with Cystinosis and from 37 neurotypical control participants and performed analyses of part of the behavioral and the electrophysiological data. In this cumulative report, we indicate major progress over the past six months, since our last report, with blue font.

Scientific communications: We presented preliminary analyses of the data at the Cystinosis Research Network Family Conference in Utah. We also presented these data at the Pediatrics Research Day and at the Lysosomal Rounds at the Albert Einstein College of Medicine and to our Lysosomal Storage Disorders Grand Rounds at Einstein/Montefiore group (April 2018), and will present them at the International Meeting of the Psychonomic Society taking place in the Netherlands (May 2018). We have started preparing the data from two of the datasets for publication, and are currently working on the first manuscript.

Recruitment Efforts: We engaged in extensive recruitment efforts through social media and during the Cystinosis Research Network Family Conference. Furthermore, enrollment capacity was greatly increased through the addition of funds from the CRN to fly families in for two days of data collection. We have met our new recruitment targets and have completed data collection. In the past year and a half, we collected data from 32 individuals diagnosed with cystinosis (19 children, 6 adolescents, and 5 adults) and from 37 neurotypical controls (16 children, 12 adolescents, and 9 adults). We propose to collect data from 9 more adults and 8 more adolescents with Cystinosis (plus healthy age matched controls) so that we may assess how perceptual and cognitive functions change over development in Cystinosis.

CRN Research Funding Update Q3 2017

September 2017 Grant Awarded

Study of Neuronal Structure and Function Changes in Cystinosis, John Foxe, PhD and Krishnan Padmanabhan, PhD

Investigators at the Department of Neuroscience Ernst J. Del Monte Institute for Neuromedicine University of Rochester School of Medicine and Dentistry Rochester, NY have outlined a research proposal taking a novel systems neuroscience strategy to address the link between molecular/cellular pathology of the lysosomal system in neurons and the resultant changes in the structure and function of neuronal circuits using new electrophysiology, imaging and computational methods to understand the effect of Cystinosis is on neural circuits. By identifying the mechanisms underlying the neuropathology of the disease at the basic science level, this research program will provide important biomarkers for tracking disease progression, could identify new sites/targets for intervention and guide in the development of strategies for treatment.

CRN Research Funding Update Q1 2017

March 2017 Grants Awarded

Year Two Study Extensions Announced

We are pleased to announce the CRN’s extended funding to support two ongoing studies. One with Principal Investigator Steven Walkley, DVM, PhD researching the affiliation between Cystinosis and brain function and the second led by Elena Levtchenko, MD, PhD to determine if potential harmful cellular events in Cystinosis may not be directly related to cystine accumulation.

Mechanisms Underlying Neurocognitive Changes in Cystinosis, John Foxe, PhD Co‐Principal Investigator, Sophie Molholm, PhD Co‐Principal Investigator, Steven U. Walkley, DVM, PhD Co‐Principal Investigator

Cystinosis has long been known for its significant impact on renal and thyroid function. It is only in recent years, however, due to the emergence of effective life-prolonging treatment regimens for these primary clinical symptoms that researchers and clinicians have been able to turn greater attention to the impacts this disease has on brain function. To date there is only limited work in this area. To address this shortcoming of knowledge, investigators in Pediatrics and Neuroscience at the Albert Einstein College of Medicine (Molholm, Walkley) and the University of Rochester Medical Center (Foxe) are evaluating individuals with Cystinosis as well as mice in which the Cystinosis gene has been knocked out. The human studies involve the use of high-density electroencephalographic (EEG) recordings of brain activity being carried out by Drs. Molholm and Foxe in Einstein’s Cognitive Neurophysiology Laboratory. Dr. John Foxe, lead investigator on the human project, reports observing a strikingly “normal” pattern of multisensory behavior and brain responses in Cystinosis, a finding that stands in stark contrast to those obtained in another lysosomal storage disorder where significant impairment is observed (Niemann-Pick type C disease). The group will continue to collect data for this study, to see if this finding holds up in a larger sample. In addition, following these “positive” results indicating intact sensory processing, they are turning to measurement of cognitive processes that require highly coordinated activity across extensive networks of cortical regions, as these are likely to be more sensitive to any neural damage incurred. For the mouse studies, spearheaded by Dr. Walkley, director of Einstein’s Sidney Weisner Laboratory of Genetic Neurological Disease, mice with genetically-induced Cystinosis have been established in a breeding colony and are being evaluated for changes in selected brain regions (hippocampus, neocortex and cerebellum) in an attempt to determine with greater precision just how this genetic disease impacts the function of individual types of brain cells. Analyses here range from exploring connectivity and the structure of individual neurons to changes in the metabolic activities secondary to the disease-induced defect in lysosomes. As phenotypic biomarkers related to Cystinosis are identified in these brain regions, the impact of treatment (e.g., with cysteamine) in preventing, delaying and/ or reversing these changes will be pursued. The ultimate goal of these tightly collaborative studies from the two labs is to more fully understand the effects that Cystinosis has on brain structure and function and how factors leading to such compromise could be alleviated.

Altered protein kinase signaling as a cause of reduced adhesion and increased motility of renal epithelial cells in Cystinosis – E. Ivanova, L. van den Heuvel, E Levtchenko (Principal Investigator)

Cystinosis is a genetic disease manifesting early in life (≈ 6-12 months) with progressive kidney disease resulting in renal failure early during childhood if not treated. In Cystinosis the metabolism of the amino acid cystine is defective leading to its accumulation in the kidney and other organs. This cystine accumulation results in cellular damage and death, but the direct mechanisms beyond this phenomenon are largely unknown. Some harmful cellular events in Cystinosis might not be directly related to cystine accumulation and are the subject of our research project. Based on our previous work we hypothesized that the loss of highly specified renal cells like glomerular podocytes and renal proximal tubular cells in urine is a major mechanism causing renal pathology of Cystinosis. Increased rate of cellular abundance in urine can be explained by either the decreased adhesion of renal cells to their matrix or their increased motility or by a combination of both mechanisms. Indeed we demonstrated that both events occur in cultured human renal cells derived from Cystinosis patients. We further tried to explore the mechanisms beyond this cellular loss. It has been reported in other diseases that increased cell motility and defective adhesion can be associated with the altered protein kinase signaling. In cystinotic podocytes we found an increased expression of activated or phosphorylated Akt kinases compared to control cells. This could explain, at least partially, the abnormal phenotype. We are currently testing other protein kinases that might contribute to this mechanism. In addition we tested the gene expression of several integrin in podocytes, as podocytes adhere to the extracellular matrix using integrin receptors. Although only minor differences were found between cystinotic and control cells, cell surface expression of these proteins still has to be studied. So far most of our experiments were done in podocytes. We recently started to investigate proximal tubular epithelial cells which also showed an increased expression of phosphorylated Akt kinases unifying the concept of the hypothesis over different renal cell types. Our future plan includes also the experimentation with different kinase inhibitors to explore if they can reverse abnormal renal phenotype.

CRN Research Funding Update 2015

November 2015 Grants Awarded

The Cystinosis Research Network is pleased to announce its grant awardees for 2016. These three grants represent one established Cystinosis researcher in Dr. Levtchenko’s group in Belgium, one esteemed neuroscience lab at Montefiore in the Bronx which is expanding their work into cystinosis, and one innovative newborn screening initiative in Germany led by Dr. Hohenfellner. The grants total over $200,000 in funding for 2016. They are:

“Mechanisms Underlying Neurocognitive Changes in Cystinosis” John Foxe, PhD, Sophie Molhom, PhD, Steven U. Walkley, DVM PhD, Co-Principal Investigators Departments of Neuroscience and Pediatrics and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY Aims for the project are to explore sensory processing and multisensory integration as potential biomarkers using high-density electrophysiological mapping techniques in individuals with Cystinosis and to determine the cell biological contributions to neuronal dysfunction in Cystinosis and their impact on neural network connectivity. Grant Year One: $98,010

“Postpartal Screening for Cystinosis with urine dipsticks at the age of 12 weeks” PD Dr. med. Katharina Hohenfellner, LÄ Kindernephrologie, Kinderklinik Traunstein, Cuno-Niggl-str.3, 83278 Traunstein, Germany Dr. med. Uta Nennstiel Ratzel MPH, Leitung Sachgebiet GE4, Präsidentin der Deutschen Gesellschaft für Screening, Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Veterinärstr.2, 85762 Oberschleißheim Prof. Dr. med. Lothar Thomas, Emeritus Direktor Laboratoriumsmedizin , Klinikum Frankfurt Höchst, 65929 Frankfurt, Germany Prof. Dr. med Erich Harms, Emeritus Direktor, Kinderklinik Münster, 48149 Münster, Germany The objective of the present study is to determine if screening with urine strips can detect patients with Cystinosis during early childhood. This study plans to test infants born in Bavaria, during the next two years, with a urine dipstick at the age of 12 weeks. If this method yields valid as a screening method for Cystinosis, we plan to integrate it into the standard German child health care examinations. Total grant: $25,000

“Altered protein kinase signaling as a cause of reduced adhesion and increased motility of renal epithelial cells in Cystinosis” E. Ivanova, L. van den Heuvel, E. Levtchenko Katholieke Universiteit Leuven, Belgium In this project, we will focus on the altered cytoskeleton and increased motility of cystinedeficient human podocytes and proximal tubular epithelial cells that may underlie the increased renal cell loss in cystinosis and the development of kidney damage. We will also further investigate the mechanisms of altered vesicular trafficking that can link disturbed endocytosis to protein kinase signalling. Finally, we will study the effects of cysteamine and various protein kinase inhibitors on the abnormal phenotype of cystinotic cells. The obtained results will contribute to the understanding of the pathogenesis of cystinosis and will help identifying novel therapeutic targets to improve the treatment of the disease. Grant Year One: $77,000

We are happy to support all three groups important work and will report results back to the community.

CRN Research Funding Update 2014

Extension of Genotype-Phenotype in Egyptian Patients with Nephropathic Cystinosis. Neveen Soliman, MD and Elena Levtchenko, MD, PhD, Center of Pediatric Nephrology and Transplantation, Cairo Univeristy, Egypt and Department of Pediatric Nephrology Univeristy Hospitals, Leuven, Belgium. Total Award: $4,400

Extension of Proteomic Investigation of Cystinotic Cells and the Effects of Cysteamine Treatment. Jill Jobson, Noel Carter, Achim Treumann, Ken McGarry and Rosaleen J. Anderson, Sunderland Pharmacy School, University of Sunderland. Total Award: $55,000

Extension of the Continuation of Feasilbility of Cystinosin Replacement Therapy in Cystinosis. Jess G. Thoene, MD, Director, Biochemical Genetics laboratory, Active Profession Emeritus of Pediatrics, University of Michigan. Total Award: $81,000

National Institutes of Health Cystinosis Fellowship, 2013 – 2015, Galina Nesterova, MD, Mentor, William A. Gahl, MD, PhD. Total Award: $130,000

CRN Research Funding Update 2013

CRN has granted new funding for three research project extensions plus an extension of the NIH Clinical Fellowship for 2013:

Rosaleen Anderson, PhD, Sunderland Pharmacy School, University of Sunderland, “Continuation of proteomic investigation of cystinotic cells and the effects of cysteamine treatment”. Total award: $54,121.23

Neveen Soliman, MD and Elena Levtchenko, MD, PhD, Center of Pediatric Nephrology and Transplantation, Cairo University, Egypt and Department of Pediatric Nephrology University Hospitals, Leuven, Belgium, “Genotype-Phenotype in Egyptian Patients with Nephropathic Cystinosis.” Total award: $20,139.00

Jess G. Thoene, MD, Director, Biochemical Genetics Laboratory, Active Professor Emeritus of Pediatrics, University of Michigan, “Extension of the Continuation of Feasibility of Cystinosin Replacement Therapy in Cystinosis.” Total award: $81,000.00

Galina Nesterova, MD, National Institutes of Health Cystinosis Fellow. Total award: $130,000.00

Ongoing projects:

Dr. C. Tuleu, University of London, School of Pharmacy, Dr. Olufemi Rabiu, Guy’s St. Thomas’ NHS Foundation Hospital, Mr. Ken K. Nischal, Mr. Rajnish Sekhri, and Dr. William Van’t Hoff, Great Ormond Street Hospital and Institute of Child Health “Development of a cysteamine in situ gelling system for the topical treatment of corneal crystals in cystinosis.” Total award:$203,500.00

Leticia Belmont, M.D., Laboratory of Inborn Errors of Metabolism and National Institute of Pediatrics, Mexico. “Determination of Intra-leucocotary Cystine by HPLC in patients with cystinosis.” Total award: $31,972.00

CRN Research Funding Update 2012

A major focus of the Cystinosis Research Network continues to be a determined effort to secure a promising future for the cystinosis community through the sup-port and funding of research grants that lead to improved treatments and ultimately a cure for cystinosis. CRN has a current research commitment of over $800,000.00 and has funded nearly $3 million total in research grants and fellowships.

Current Research Studies:

Neveen Soliman, MD and Elena Levtchenko, MD, PhD, Center of Pediatric Nephrology and Transplantation, Cairo University, Egypt and Department of Pediatric Nephrology University Hospitals, Leuven, Belgium, “Genotype-Phenotype in Egyp-tian Patients with Nephropathic Cystinosis”, Grant awarded March 2012 for a 12 month period. Total award: $15,750.

Martine Besouw, MD, Department of Women and Child Laboratory of Pediatrics, University Hospitals, Leuven Belgium, “Study of skin changes in cystinosis patients under cysteamine therapy”, Mentor: Elena Levtchenko, MD, PhD. Grant awarded 6 December 2011 for a 12 month period. Total Award: $99,400.00. This grant is a joint funding collaboration between Cystinosis Research Network and Cystinosis Foundation Ireland.

Maya Doyle, LCSW, Children’s Hospital at Montefiore, Division of Pediatric Nephrology, New York University, “Cystinosis in Emerging Adulthood”. A one-time grant awarded on 24 July 2011 for a total of $17,200.

Jess G. Thoene, M.D, Director, Biochemical Genetics Laboratory, Active Professor Emeritus of Pediatrics, University of Michigan, “Continuation of Feasibility of Cystinosin Replacement Therapy in Cystinosis”, Grant awarded 24 July 2011 for an 18 month period for $202,500.00.

Rosaleen Anderson, PhD, Sunderland Pharmacy School, University of Sunderland, “Proteomic investigation of cystinotic cells and the effects of cysteamine treatment”. Grant awarded: 23 November 2010 for a term of 2 years in the amount of GPB 80,926.00 or $130,366.00 based on the exchange rate for 15 November 2010.

Catherine Tuleu, Ph.D, Ken Nischal, Olufemi Rabiu, Rajnish Sekhri, William Van’t Hoff, Univ. of London, School of Pharmacy; “Development of cysteamine in situ gelling system for the topical treatment of corneal crystals in cystinosis”, Grant awarded January 2007 for 3 years. Total award: 103,000.00 pounds or approximately $203,500.00.

Leticia Belmont, M.D, Unidad de Genetica de la Nutrician, Instituto Nacional de Pediatria, Mexico. “Determination of Intraleucocitary Cystine by High Performance Liquid Cromatography (HPLC) in Patients with Cystinosis”. Grant Awarded: 5 November 2008 Total award: $31,972.00; A presentation, citing CRN funding, was given at the IPNA mee-ting in NYC, 31 August 2010.

Henk J. Blom, M.D., M.M.C. Wamelink, and E. Levtchenko, M.D., VU University Medi-cal Center, Amsterdam, The Netherlands: “Newborn Screening of Cystinosis”. Grant Awarded: 5 November 2008; Total Award: 45,000 euros (approximately $67,500.00.

Francisco Emma, M.D. and Anna Taranta, Ph.D., Bambino Gesu Children’s Hospital and Research Institute, Rome, Italy: “Functional Characterization of Cystinosin LKG”. Grant Awarded: 5 November 2008; Total Award: $114,480.00.

Ewa Elenberg, M.D., Texas Children’s Hospital, Houston, TX “Quality of Life in Cystinosis Patients”, Grant awarded 9-25-09 for 1 year . Total award: $21,000.00

CRN Research Funding Update 2011

CRN’s Research Committee oversees the research interests of the organization and is responsible for the strategic direction in all areas of research. An official Call for Proposals is issued once a year and researchers are encouraged to submit their requests for funding for grants that offer the promise of achieving CRN’s goals of improved treatment and a cure for cystinosis. All proposals received are reviewed by CRN’s Scientific Review Board and funds are granted based on the recommendation of the Board. The 2011 grant proposal requests were reviewed by the Scientific Review Board this past July, 2011 in conjunction with CRN’s Family Conference, and we are proud to announce that the following new grants have been awarded:

Maya Doyle, LCSW, Children’s Hospital at Montefiore, Division of Pediatric Nephrology, New York University, Cystinosis in Emerging Adulthood.. One time grant of $17,200.00 awarded July 2011; payment processed 17 August 2011. Study and payment complete.

Jess G. Thoene, M.D, Director, Biochemical Genetics Laboratory, Active Professor Emeritus of Pediatrics, University of Michigan, Continuation of Feasibility of Cystinosin Replacement Therapy in Cystinosis.. Grant awarded 24 July 2011 for an 18 month period for $202,500.00. Initial payment processed 17 August 2011.

Martine Besouw, MD, Elena Levtchenko, MD, PhD; Lambertus vanden Heuvel, PhD, Univ. Medical Center Nijmegen, The Netherlands, “Study of skin changes in cystinosis patients under cysteamine therapy.. Grant awarded October 2011 for a 12 month period for $90,400.00 Co-funded by Cystinosis Foundation Ireland.

Recently completed Research Grants:

Dr. Paul Goodyer, Montreal Children’s Hospital, Montreal, Canada, and Dr. Rick Kaskel, Children’s Hospital at Montefiore, Bronx, NY. “Proposal for a North American Cystinosis Research Platform”. One year grant of $36,000.00 awarded for development.

Jess Thoene, MD, Univ. of Michigan, Ann Arbor, Tissue Repository for Cystinosis. Grant awarded: Start date: Nov. 2006 Total award: $26,206.00. Final report recd 15 Sept 2010.

Viki Kalatzis, PhD, Eric J. Kremer, PhD, Institut Genetique Moleculaire de Montpellier, France, Gene transfer studies for cystinosis. Grant awarded 29 Aug 2007, 2 yrs. Total award: Euros 75,900.00, approx. US$104,619.48. Final report received 25 November 2009.

Jess Thoene, M.D., University of Michigan, Ann Arbor, MI, “Feasibility of Cystinosin Replacement Therapy in Cystinosis”, Grant awarded 9-25-09 for two years (9-1-09 to 8-31-11) Total Award: $165,732. Final report received August 31, 2011, Final payment of $55,247.00.

CRN Research Grants in Progress as of July, 2011:

Rosaleen Anderson, PhD, Sunderland Pharmacy School, University of Sunderland, “Proteomic investigation of cystinotic cells and the effects of cysteamine treatment”. Grant awarded: 23 November 2010 for a term of 2 years in the amount of GPB 80,926.00 or $130,366 based on the exchange rate for 15 November 2010.

Elena Levtchenko, MD, PhD Univ. Medical Center Nijmegen, The Netherlands, Study of ATP metabolism in human cystinotic proximal tubular cells and in humans with cystinosis in vivo. Grant awarded: 11 September 2006. Total award: $68,090.00 Balance remaining on grant: $17,022.50 A Final report was received on 5 February 2009. However, Dr. Levtchenko has indicated that the In vivo part of this project is not finished yet due to the technical difficulties with the MRS apparatus, but we have good hope that the problem will be solved and this part of the study will be finished in 2009..

Catherine Tuleu, PhD, Ken Nischal, Olufemi Rabiu, Rajnish Sekhri, Wm Van’t Hoff, MD Univ. of London, School of Pharmacy; Development of cysteamine in situ gelling system for the topical treatment of corneal crystals in cystinosis., Grant awarded January 2007 for 3 years. Total award: 103,000.00 pounds or approximately $203,500.00. Balance remaining on grant approximately $71,703.09.

Leticia Belmont, M.D., Unidad de Genetica de la Nutrician, Instituto Nacional de Pediatria, Mexico. Determination of Intraleucocitary Cystine by High Performance Liquid Cromatography (HPLC) in Patients with Cystinosis. Grant Awarded: 5 November 2008 Total award: $31,972.00; Balance re-maining on grant: $15,986.00. Presentation, citing CRN funding, was given at the IPNA meeting in NYC, 31 August 2010. Progress report Sept. 2010

Henk J. Blom, M.D., M.M.C. Wamelink, and E. Levtchenko, VU University Medical Center, Amsterdam, The Netherlands: Newborn Screening of Cystinosis.. Grant Awarded: 5 November 2008; Total Award: 45,000 euros (approximately $67,500.00); Balance remaining on grant: 33,750 euros

Francisco Emma, M.D. and Anna Taranta, Ph.D., Bambino Gesu Childrens Hospital and Research Institute, Rome, Italy: Functional Characterization of Cystinosin-LKG.. Grant Awarded: 5 November 2008; Total Award: $114,480.00; Balance remaining on grant: $21,465.00

Ewa Elenberg, MD, Texas Children’s Hospital, Houston, TX “Quality of Life in Cystinosis Patients”, Grant awarded 9-25-09 for 1 year . Total award: $21,000.00 Balance remain-ing on grant: $7,875.00.

CRN Funds New Research Project

Rosaleen Anderson, PhD, Sunderland Pharmacy School, University of Sunderland, “Proteomic investigation of cystinotic cells and the effects of cysteamine treatment”. Grant awarded: 23 November 2010 for a term of 2 years in the amount of GPB 80,926.00 or $130,366 based on the exchange rate for 15 November 2010.

Ongoing Research Commitments

Jess Thoene, MD, Univ. of Michigan, Ann Arbor, “Tissue Repository for Cystinosis” Grant awarded: 30 August 2005, interrupted immediately by hurricane Katrina. New start date: 21 Nov. 2006 – ongoing. Total award: $26,206.00

Elena Levtchenko, MD, PhD Univ. Medical Center Nijmegen, The Netherlands, “Study of ATP metabolism in human cystinotic proximal tubular cells and in humans with cystinosis in vivo” Grant awarded: 11 September 2006 for 1 year, Jan. 2007 thru Dec. 2007. Total award: $68,090.00. A “Final report” for this study was received 5 February 2009. However, an email from Dr. Levtchenko indicated that the “In vivo part of this project is not finished yet due to the technical difficulties with the MRS apparatus, but we have good hope that the problem will be solved and this part of the study will be finished in 2009”. CRN acknowledged receipt of this report, but has not accepted it as a “final” report. Dr. Levtchenko is now associated with the Department of Pediatric Nephrology, University Hospital, Leuven, Belgium.

Catherine Tuleu, PhD Univ. of London, School of Pharmacy (other names on grant: Ken Nischal, Olufemi Rabiu, Rajnish Sekhri, Wm Van’t Hoff and Bola Lawal) “Development of cysteamine in situ gelling system for the topical treatment of corneal crystals in cystinosis”, Agreement signed 24 Oct. 2006; Grant awarded January 2007 for 3 years, 1 Mar 2007 – Feb. 2010.

Leticia Belmont, M.D., Unidad de Genetica de la Nutrician, Instituto Nacional de Pediatria, Mexico. “Determination of Intraleucocitary Cystine by High Performance Liquid Cromatography (HPLC) in Patients with Cystinosis”. Grant Awarded: 5 November 2008 for 1 year (Fall ’08 – Fall ’09) Total award: $31,972.00.

Henk J. Blom, M.D., M.M.C. Wamelink, and E. Levtchenko, VU University Medical Center, Amsterdam, The Netherlands: “Newborn Screening of Cystinosis”. Grant Awarded: 5 November 2008 for 18 months (Fall 2008 – Spring 2010). Total Award: 45,000 euros (approximately $67,500.00 — approximately 60,818.71 USD, as calculated 3-2010).

Francisco Emma, M.D. and Anna Taranta, Ph.D., Bambino Gesu Children’s Hospital and Research Institute, Rome, Italy: “Functional Characterization of Cystinosin-LKG”. Grant Awarded: 5 November 2008 for 2 years (January 2009 – December 2010). Total Award: $114,480.00.

Jess Thoene, M.D., University of Michigan, Ann Arbor, MI, “Feasibility of Cystinosin Replacement Therapy in Cystinosis”, Grant awarded 9-25-09 for two years (9-1-09 to 8-31-11) Total Award: $165,732.00.

Dr. Ewa Elenberg, Texas Children’s Hospital, Houston, TX “Quality of Life in Cystinosis Patients”, Grant awarded 9-25-09 for 1 year (10-1-09 to 9-30-10) Total award: $21,000.00. Dr. Paul Goodyer, Montreal Children’s Hospital, Montreal, Canada, and Dr. Rick Kaskel, Children’s Hospital at Montefiore, Bronx, NY. “Proposal for a North American Cystinosis Research Platform”. One year grant of $36,000.00 awarded for development.

CRN Funds 3 New Research Projects

September 29, 2009
The Cystinosis Research Network is happy to announce that it will provide funding for three new research projects as a result of it’s 2009 Call for Proposals. These studies represent an additional $250,000 in research funding, putting CRN’s current research funding commitment at $1.3 million dollars. The three new projects funded are: “Feasibility of Cystinosin Replacement Therapy in Cystinosis”, Dr. Jess Thoene, University of Michigan, Ann Arbor, MI “Quality of Life in Cystinosis Patients”, Dr. Ewa Elenberg, Texas Children’s Hospital, Houston, TX “Proposal for a North American Cystinosis Research Platform”, Dr. Paul Goodyer, Montreal Children’s Hospital, Montreal, Canada, and Dr. Rick Kaskel, Children’s Hospital at Montefiore, Bronx, NY We welcome Dr. Elenberg, Dr. Kaskel, and Dr. Goodyer as new CRN funded investigators, and we look forward to our continued relationship with Dr. Thoene. We also wish to thank the CRN Scientific Review Board for their thoughtful review and recommendations regarding this years’ submitted proposals.

CRN Grants $250,000 In New Research Funding

The Cystinosis Research Network’s vision is the discovery of improved treatments and ultimately a cure for cystinosis. With that thought in mind, CRN issued our annual Call for Research Proposals in the Spring of 2008; and, it is with great pleasure that we can now present to you the latest additions to CRN’s research team, totaling nearly $250,000 in new research funding! CRN and the cystinosis community are so very fortunate to have the experience and expertise of these dedicated researchers included in our pursuit of a better life for the cystinosis patient.

Leticia Belmont Martinez, M.D., Unidad de Genetica de la Nutricion, Instituto Nacional de Pediatria, Mexico. “Determination of Intraleucocitary Cystine by High Performance Liquid Cromatography (HPLC) in Patients with Cystinosis”; one year study; total grant: $31,972.00.

Henk J. Blom, M.D. et al, VU University Medical Center, Amsterdam, The Netherlands. “Newborn Screening of Cystinosis”; 18 month study; total grant: 45,000 euros, approximately $67,500.00

Francisco Emma, M.D. and Anna Taranta, Ph.D., Bambino Gesu Children’s Hospital and Research Institute, Rome, Italy. “Functional Characterization of Cystinosin-LKG”; 2 year study; total grant: $114,480.00.

CRN is very proud to welcome these new researchers! They join that unique group of professionals who have been involved in past and on-going research studies funded by CRN. It is because of the dedication and perseverance of all these researchers that so much progress has been made in the treatment and improved outlook for our cystinosis patients

The addition of these research grants brings CRN’s current research commitment to a total of nearly $1,000,000! It because of your continued support, and that of the cystinosis community through contributions and fundraisers, that CRN can make this research possible.