Orphan Disease Center

ODC Funding Opportunities



2017 Million Dollar Bike Ride Pilot Grant Program: Request for Applications

The 2017 Million Dollar Bike Ride Pilot Grant Program is now open!  The MDBR Pilot Grant Program provides a one-year grant to support research related to a rare disease represented in the 2017 Million Dollar Bike Ride.  Thirty-three (33) total grant opportunities are listed below. Number of awards and dollar amounts vary per disease based on fundraising totals by each disease team.  

Eligibility: All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.  

To Apply:  Please review the RFA guidelines here.  Interested applicants must first submit a Letter of Interest (LOI) which can be found here.  This LOI is due by Monday, September 18, 2017 by 8pm EST.   Full applications are accepted by invitation only after LOIs are approved. 

Research Focus Areas for Pilot Grants:

1) Adrenoleukodystrophy (ALD): One $101,164 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Grants should focus on activities that lead towards a clinical trial.  Adrenoleukodystrophy (ALD) is an X-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

2) Adult Polyglucosan Body Disease (APBD): Two $52,978 grants are available to initiate or advance research of a treatment or a cure for this glycogen storage disease. These grants are made possible by the Tour de Friends bike team with the APBD Research Foundation.

3) Ataxia-Telangiectasia: One $65,689 grant is available to identify and test therapeutic strategies for the neurodegeneration and motor control problems faced by patients affected by Ataxia-Telangiectasia. Projects may involve early, preclinical studies such as target identification, phenotypic screening, gene therapy vectors or the elucidation of disrupted neurocircuitry but must be novel and have a clear path for translation to a therapy. This grant is made possible by Team Derek’s Dreams and the A-T Children’s Project.

4) BPAN- A Neurodegeneration with Brain Iron Accumulation Disorder: Two $50,507 pilot grants are available for clinical and translational research studies related to the detection, diagnosis, or treatment of this rare, X-linked disorder caused by mutations in WDR45. BPAN typically is recognized in early childhood with delayed development and seizures. In adulthood, people with BPAN develop rapidly progressive parkinsonism. At the present time, symptoms may be treated but there are no cures.

Grants are expected to generate essential resources for the scientific community, advance knowledge about BPAN disease processes, and produce preliminary data to enable national and international funding to carry the work forward. Examples of priority topic areas include developing disease models that complement existing models, identifying biomarkers, delineating the molecular cascade that leads to early cellular changes, developing rational therapeutics, establishing outcome measures to be used in clinical trials, and developing other essential resources to substantially prepare the BPAN community for clinical trials. Natural history studies must have a component that includes participation in the International NBIA Patient Registry & Biobank. These grants are made possible by Team NBIA and BPAN families with the NBIA Disorders Association.

5) Castleman Disease: A $42,508 pilot grant is available to perform critical investigations into the etiology and pathogenesis of HHV-8-negative/"idiopathic" multicentric Castleman disease (iMCD). We seek to fund research that will improve understanding of the etiology, genomic aberrations, aberrant cell populations, dysregulated signaling pathways, and/or effector cytokines in iMCD. Applications that include strong preliminary data from discovery-level studies that need funding for targeted function characterizations of suspected pathological genomic aberration(s) are preferred. Functional validation studies should provide information on the genomic aberration identified, functional studies to demonstrate the effect of the aberration and hypothesized mechanisms for how the aberration leads to iMCD pathogenesis. If preliminary data suggests that the aberration is acquired, proposals should also include studies to identify the harboring cell population. The Castleman Disease Collaborative Network (CDCN) will support the project through sample procurement, as needed, and can provide its expertise and guidance to facilitate the success of the project.  This grant is made possible by the Castleman Disease Collaborative Network and Team CDCN. 

6) CDKL5: Two $51,160 grants are available, made possible by The International Foundation for CDKL5 Research and Team CDKL5.

  1. CDKL5 Postmortem Brain Samples ($51,160): Research focused on genetic, molecular and anatomical studies of postmortem brain samples of CDKL5.   There are CDKL5 postmortem samples at the Harvard Brain Bank under the Rett Syndrome special collection.  This area is completely underrepresented in any current CDKL5 research, and can inform the future of other aspects of CDKL5 research.  IFCR will assist the awardee with gaining access to this tissue.
  1. Mechanisms of CDKL5 Seizure Activity ($51,160): Research focused on seizures in CDKL5, including but not limited to causation, treatment, or evaluation.  This can include drug screening.

7) Congenital Hyperinsulinism (CHI): One $87,109 grant available for an innovative, pre-clinical or clinical study that has the potential to lead to: (1) faster and more accurate diagnoses of congenital hyperinsulinism (HI); (2) better HI treatment; (3) a cure for HI; or (4) quality of life improvement for those affected by HI. This grant is made possible by Team Raring to Go for CHI, and Congenital Hyperinsulinism International.

8) Congenital Muscular Dystrophy (CMD): One $41,831 grant available. CMD are a group of genetically inherited multi-system disorder with symptom onset at birth and progressive muscle weakness, respiratory insufficiency, contractures and scoliosis.  Failure to thrive, cardiac arrhythmias, subclinical cardiomyopathy and seizures may complicate disease course. The purpose of this RFA is to promote discovery of underlying disease mechanisms and preclinical development of potential therapies, as well as the clinical translation of those efforts.  Areas of interest include, but are not limited to, understanding the cause of disease, unraveling pathways involved in disease, identifying novel drug targets or gene therapies, and testing new strategies to treat disease or any of its incapacitating consequences (e.g. contractures).  In addition, applications may propose to create or improve disease models (e.g. animal models, patient-derived cell models), biomarkers or functional outcome measures to asses therapeutic impact. Priority will be given to research projects targeting Collagen VI (Ullrich).  This grant is made possible by Team Cure CMD and the Cure CMD organization. 

9) CRB1 degenerative retinal disease: Two $50,497 grants are available for work toward treatments for CRB1 retinal disease. Applications including gene therapy, CRISPR, cell therapy or other methods that will halt the progression of CRB1 retinal disease and ultimately restore retinal function will be considered. CRB1 retinal disease is a rare disease causing Leber’s Congenital Amaurosis (LCA), Retinitis Pigmentosa (RP) or Cone Rod Dystrophy. Children with CRB1 are blind or visually impaired from a very early age (at birth in LCA) and most are Braille readers and white cane users. This grant is made possible by Team Bike4Sight and the Curing Retinal Blindness Foundation

10) Nonsense Mutations in Cystic Fibrosis: One $52,985 grant available. Cystic fibrosis is a genetic condition affecting the lungs and digestive system. The grant will be awarded to advance research and understanding of a treatment or cure that would impact people carrying a nonsense mutation.  The research should include, but not be limited to, the R1158X gene mutation. This grant is made possible by Team Movin’ for Mallory: Cure Cystic Fibrosis! and the Movin’ for Mallory organization.

11) Dyskeratosis Congenita & Telomere Biology Disorder: One $48,191 pilot grant available to investigators conducting clinical studies or basic science research on all aspects of Dyskeratosis Congenita or Telomere Biology Disorders. Dyskeratosis Congenita is a progressive, genetic condition caused by defects in telomere biology and results in problems in areas with high rates of cell regeneration. Proposals that seek to advance understanding of the manifestations of the disease will be considered. This research could involve the examination of late effects of the disease—including late effects of stem cell transplant; the development of a comprehensive database that characterizes clinical complications and or treatments; focus on gene discovery; or address any of the unmet needs of DC/TBD patients. This grant is made possible by Team Josh & the DCO Riders and Dyskeratosis Congenita Outreach, Inc.

12) Fibrous Dysplasia/McCune Albright Syndrome: Two grants available, each for up to $53,614. Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disease caused by somatic mutations in GNAS. The mutation results in constitutive activation of the signaling protein, Gsα, and downstream cAMP signaling. Skeletal manifestations include bone pain, fractures, deformity, and osteomalacia/rickets. Any study that focuses on the pathogenesis of FD/MAS, or clinical investigative studies to address any of the unmet needs in FD/MAS patients and their management will be considered. Research priorities for the Fibrous Dysplasia Foundation include: generation of new mouse models to study FD/MAS; studies to understand the mechanism and/or treatment of FD-related bone pain; development/testing of therapeutics, especially those targeting Gsα, PKA or Wnt signaling pathways, including through the use of oligonucleotides; or studies of the molecular etiology, especially the role of RANKL, IL6, cAMP and FGF23. These grants are made possible by Team FD and the Fibrous Dysplasia Foundation.

13) Generalized Lymphatic Anomaly (GLA; a.k.a. lymphangiomatosis) and Gorham-Stout Disease (GSD): Two grants are available for basic science and/or clinical research on GSD or GLA. One is for $80,185 and the other is for $52,109. Areas of interest include, but are not limited to, genetic analysis, biomarker identification, cell line creation and characterization, and imaging. These grants are made possible by Team LGDA (Lymphangiomatosis & Gorham’s Disease Alliance) and Team LMI (Lymphatic Malformation Institute).

14) Glucose Transporter Deficiency Syndrome (Glut 1DS): Glut 1 DS is a rare genetic disorder caused by a mutation in the SLC2A1 gene, which regulates the glucose transporter type 1 (Glut1).  Glucose is not transported properly into the brain, leaving it starving for the energy it needs to grow & function.   One $48,918 pilot grant is available and will be awarded to research focused on identifying and investigating innovative research projects that involve basic research including blood brain barrier, translational studies, clinical studies, alternative treatment theory, or gene therapy relevant to Glut 1DS.  This grant is made possible by the generous support by friends of Team Miles for Millie. 

15) Lymphangioleiomyomatosis (LAM): Two $50,060 pilot grants will be available focusing on translational proposals with strong likelihood of future federal funding, that use LAM samples, models or patient data, and which have the potential to favorably impact human health will be given priority. Examples of desirable topic areas include identification of molecular targets, biomarker development, and biomarker driven small pilot trials. In 2017, LAM research grant proposals from early career investigators (three years or less into their first faculty appointment) who are working in the laboratories of established LAM researchers or conducting research with the mentorship of established LAM researchers will be given priority. These grants are made possible by Team LAM Foundation Easy Breathers and The LAM Foundation. 

16) Mucolipidosis Type IV (ML4):  One $71,939 pilot grant available. Mucolipidosis Type IV is caused by a single-gene mutation in p19 which encodes for MCLON1. Most patients experience total loss of this transmembrane protein resulting in severe psycho-motor delays, neurodegeneration, and blindness. We offer this grant to investigators conducting research on all aspects of disease including disease pathogenesis and clinical studies. Preference will be given to those research projects developing new therapies for MLIV, and translational research projects that improve our understanding of the disease state and pathogenesis, such as biomarkers or functional outcome measures to assess therapeutic impact. This grant is made possible by Together4Ido, TeamCureML4, Climb4Carin, Pedal4Paul, Danny4theGirls, and MayaanHikes4Meira.

17) Mucopolysaccharidoses (MPS): Two $59,449 pilot grants available. Mucopolysaccharidoses represent a broad array of diseases due to enzyme defects that lead to abnormal metabolic storage products and multi-organ pathologies. We are seeking applications directed to treating the central nervous system manifestations or antibody response of these diseases. These grants are made possible by Team MPS, the National MPS Society and the Ryan Foundation.

18) Niemann Pick Type C (NPC): Two $49,645 pilot grants available. Consideration will be given to research projects developing new therapies for NPC as well as those designed to complement therapies presently in the pipeline.  Consideration will further be given to gene therapy proposals; studies focused on problems, including psychiatric issues, impacting quality of life through the lifespan of the patient population and research projects that improve our understanding of the biology, pathogenesis and disease state (i.e., biomarkers or functional outcome measures to assess therapeutic impact) and have a direct impact on translation of new treatments to patients.  This grant is made possible by Team NPC, the Andrew Coppola Foundation, Jammin' for JP, Chase the Cure and iPedal4Chad.

19) Pitt Hopkins Syndrome (PTHS): Two $49,263 pilot grants available. Pitt Hopkins Syndrome is due to a deficiency in the TCF4 gene and is characterized by severe intellectual disability and developmental delay. Other symptoms include episodic hyperventilation and/or breath-holding (55%-60%), recurrent seizures/epilepsy (40%-50%), gastrointestinal issues, and distinctive facial features. The Pitt Hopkins Research Foundation would like to focus this research on finding therapeutics and a cure for this debilitating syndrome and are not interested in natural history studies at this time. These grants are made possible by Team Pitt Hopkins Pedalers with the Pitt Hopkins Research Foundation. 

20) RASopathies: One $47,189 pilot grant available. RASopathies are a group of genetic conditions caused by mutations in genes on the Ras-MAPK pathway. These conditions, including Noonan syndrome/Noonan-related conditions (NS), cardio-facio-cutaneous syndrome (CFC), Costello syndrome (CS), and Neurofibromatosis type 1 (NF1) share many clinical features, such as developmental delay, gastrointestinal difficulties, skeletal abnormalities, hematologic abnormalities, and growth delay.

This grant should be directed toward the development of a treatment or cure for the RASopathies, and must include NS, CFC, and CS. This grant is made possible by Team RASopathies Network Riders and the RASopathies Network.

21) Snyder-Robinson Syndrome: Snyder-Robinson Syndrome (SRS) is a genetic condition resulting in the dysfunction of Spermine Synthase (SMS).  This enzyme conversion is the last step in the polyamine pathway.  Polyamines are ubiquitous and SRS is the only known condition involving a polyamine inborn error of metabolism.  Clinical features include intellectual disability, seizures, developmental delay, and osteoporosis with fractures in the absence of trauma, along with defects in other organ systems.  There is a wide range of severity among individuals with SRS.

Two $42,866 grants are available for Snyder-Robinson Syndrome.  Research focus includes further understanding of pathophysiology and/or mechanisms by which SRS causes disease as well as potential treatments, which will cure and/or improve quality of life of those with SRS. These grants are made possible by the Snyder-Robinson Team and the Snyder-Robinson Foundation.

22) Tay-Sachs, Sandhoff, GM-1, or Canavan Disease: One $42,419 pilot grant is available focusing on forms of Tay-Sachs, Sandhoff, GM-1, or Canavan disease. We are soliciting proposals for innovative research projects that involve basic research, translational studies or clinical studies relevant to the diseases mentioned above.  Projects may be focused on (1) pre-clinical and clinical research needs, such as clinical outcome measures, registries, animal models, or biomarkers or (2) technology approaches such as stem cells, molecular chaperones, substrate inhibitors, small molecule drug screening, gene therapy, novel drug delivery to the brain. This grant is made possible by Team NTSAD and the National Tay-Sachs & Allied Diseases Association.


Request for Applications to Establish New Porcine Models of Human Diseases

The application process for this grant program is now closed. Thank you to all those who participated. 

Please note: This funding opportunity is only open to Penn, CHOP and Wistar Institute Faculty. 

The Orphan Disease Center is excited by the enthusiasm that Dr. Randy Prather and Dr. Kevin Wells from University of Missouri (UM) received by the Penn community during their recent trip to Philadelphia. Drs. Prather and Wells established the National Swine Resource and Research Center (NSRRC) in 2003 and developed the infrastructure to ensure that biomedical investigators have access to critically needed swine models of human health and disease. The NSRRC creates genetically modified swine, and information and training related to use of swine models in biomedical research http://nsrrc.missouri.edu.  We are looking forward to beginning this collaboration with the NSRRC.

The next step is to take inventory of all possible projects of interest to Penn faculty. The general structure of the NSRRC collaboration is for the Orphan Disease Center to fund the generation of the transgenic porcine line at UM, after which the requesting faculty member would assume all costs of expanding the colony and conducting experiments. The limited space available to house pigs on our campus may become a bottleneck. We are working with Penn leadership to consider ways to address this issue; it should not deter you from submitting an RFA.


2017 CDKL5 Program of Excellence Pilot Grant Program

The application process for this grant program is now closed. Thank you to all those who participated. 

Background

CDKL5 Deficiency is a monogenic, orphan condition characterized by treatment-resistant epilepsy and severe cognitive and motor disability. The disease is driven by the loss of a kinase called CDKL5 which is responsible for normal neuronal development, synapse formation and signal transmission. The mechanism(s) by which CDKL5 Deficiency leads to CNS disease is unclear. The gene encoding this protein is located on the X chromosome with heterozygous females primarily affected.  The disease does not exhibit neurodegeneration and animal models strongly suggest the potential for reversibility. There are no approved therapies and standard of care is not effective at managing seizures or improving cognitive or motor deficits.

We are seeking grant applications that progress the discovery or development of treatments and/or a cure for CDKL5 Deficiency. We recognize, however, that many gaps exist in the basic understanding of CDKL5 and its role in neurologic development. Therefore basic science projects that address these gaps are welcome as long as they are tethered to the development of a potential therapy. While the RFA is broad in scope, priority will be given to grants that cover the following areas:

  1. Development of translational biomarkers in humans and animal models of CDKL5 Deficiency.
  1. Advanced understanding of CDKL5 function or disease pathophysiology to enable therapeutic development (Suggestions: Identification of kinase substrates and CDKL5 pathways; X-inactivation and skewing in the context of CDKL5 mutations; CDKL5 pathogenesis to determine if cell-autonomous or circuit level dysfunction; determine the level of upregulation necessary to achieve therapeutic benefit).
  1. Identification of therapeutic small and large-molecules for the treatment of CDKL5 Deficiency, including: development of cellular assays for compound screening; identification of genetic modifiers.
  1. Novel therapeutic approaches for CDKL5 Deficiency, including small molecules, biologics, molecular therapies, etc.
  1. Development of animal models or reporter assays and their use in defining pathogenesis and evaluating novel therapeutics. The goal of disease model development should be to enable translational research by the investigator, as well as the broader community. For this type of proposal, please include a plan for sharing and a statement of timelines for sharing the established model.

Eligibility

All individuals holding a faculty‐level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA. Biopharmaceutical companies are not eligible to apply, however, we will consider applications from contract research organizations who provide services that are responsive to the RFA.

To Apply

Please review the RFA Guidelines here: 2017 CDKL5 Funding Opportunity.pdf

Full applications can by submitted by invitation only.  If you have been notified to submit a full application, please use the following templates and submit via the form below:

Full Application Template

Detailed Budget Template

Full Application Submission Form 

 


2016 Million Dollar Bike Ride Grants

The application process for this grant program is now closed. Thank you to all those who participated. 

 

Research Focus Areas for Pilot Grants:

1) Adult Polyglucosan Body Disease (APBD): Two $50,500 grants are available to initiate or advance research of a treatment or a cure for this glycogen storage disease. These grants are made possible by the Tour de Friends and DiMauro Dream Teams with the APBD Research Foundation.

2) Adrenoleukodystrophy (ALD): One $100,000 pilot grant is available with a focus on a path towards treatment for Adrenomyeloneuropathy (AMN). Adrenoleukodystrophy (ALD) is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, Adrenomyeloneuropathy (AMN), develops in young adulthood and in general, progresses more slowly than ALD. Beginning in their 20s and 30s, men and ~60% of women carriers exhibit neurological-based motor lesions in their extremities. These lesions progress over many years and are characterized by progressive spasticity, ataxia, incontinence, and sexual dysfunction that can also be accompanied by fatigue and depression. ALD/AMN can lead to severe disability. All current treatments are symptomatic and do not address the progressive nature of the disease. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

3) Ataxia-Telangiectasia:  One $69,000 grant is available to identify and test therapeutic strategies for the neurodegeneration and motor control problems faced by patients affected by Ataxia-Telangiectasia. Projects may involve early, preclinical studies such as target identification, phenotypic screening, gene therapy vectors or the elucidation of disrupted neurocircuitry but must be novel and have a clear path for translation to a therapy. This grant is made possible by Team Derek’s Dreams and the A-T Children’s Project.

4) Castleman Disease: One $43,000 grant available. Looking for somatic mutations in HHV-8-negative or "idiopathic" multicentric Castleman disease (iMCD) lymph nodes. Proposals would first seek to identify somatic mutations from patient samples, and second would seek to validate any observed somatic mutations through functional studies. Approaches to identify somatic mutations could start with a targeted "tumor sequencing" panel on lymph node tissue, followed by validation of mutations with Whole Exome Sequencing or Whole Genome Sequencing, along with appropriate bioinformatics, on lymph nodes and germline. Studies proposing larger sample sizes (20+) will be considered more favorably than studies proposing smaller sample sizes. We expect the investigator to provide some of the samples and to contact the Castleman Disease Collaborative Network (CDCN) to help identify additional samples. This grant is made possible by Team Castleman Disease and the CDCN.

5) CFTR Nonsense Mutations: One $53,000 grant available.  A pilot project grant will be awarded to academic researchers to initiate or advance research and understanding of a treatment or a cure that would impact the nonsense mutation 1282X in the CFTR gene. The research could include drug discovery or other strategies to restore 1282X CFTR function, including suppression of premature termination, modulation of nonsense mediated decay and gene editing. This grant is made possible by Team Emily’s Entourage and the Emily’s Entourage organization.  

6) Congenital Hyperinsulinism (CHI): One $82,000 grant available focusing on innovative, pre-clinical or clinical studies designed to improve the diagnosis, therapy, or quality of life for those affected by congenital hyperinsulinism.  This grant is made possible by Team Raring to Go for CHI, and Congenital Hyperinsulinism International.

7) Congenital Muscular Dystrophy (CMD) One $47,000 grant available.  CMD are a group of genetically inherited multi-system disorder with symptom onset at birth and progressive muscle weakness, respiratory insufficiency, contractures and scoliosis. Failure to thrive, cardiac arrhythmias, subclinical cardiomyopathy and seizures may complicate disease course. The purpose of this RFA is to evaluate underlying disease mechanisms that might prove to be targetable by drugs or an intervention. The funding will be used to generate preliminary data of sufficient quality to evaluate the plausibility of additional preclinical testing. This grant is made possible by Team Cure CMD and the Cure CMD organization.

8) CRB1 degenerative retinal disease: Two $50,500 grants are available for work toward treatments for CRB1 retinal disease.  Applications including gene therapy, CRISPR, cell therapy or other methods that will halt the progression of CRB1 retinal disease and ultimately restore retinal function will be considered.  CRB1 retinal disease is a rare disease causing Leber’s Congenital Amaurosis (LCA), Retinitis Pigmentosa (RP) or Cone Rod Dystrophy. Children with CRB1 are blind or visually impaired from a very early age (at birth in LCA) and most are Braille readers and white cane users. This grant is made possible by Team Bike4Sight and the Curing Retinal Blindness Foundation. 

9) Nonsense Mutations in Cystic Fibrosis: One $63,000 grant available. Cystic fibrosis is a genetic condition affecting the lungs and digestive system. The grant will be awarded to advance research and understanding of a treatment or cure that would impact people carrying a nonsense mutation.  The research should include, but not be limited to, the R1158X gene mutation. This grant is made possible by Team Movin’ for Mallory: Cure Cystic Fibrosis! and the Movin’ for Mallory organization.

10) Dyskeratosis Congenita & Telomere Biology Disorder:  One $51,000 pilot grant available to investigators conducting clinical studies or basic science research on all aspects of dyskeratosis congenita or telomere biology disorders. Dyskeratosis Congenita is a progressive, genetic condition caused by defects in telomere biology and results in problems in areas with high rates of cell regeneration. Proposals that seek to advance understanding of the manifestations of the disease will be considered. This research could involve the examination of late effects of the disease—including late effects of stem cell transplant; the development of a comprehensive database that characterizes clinical complications and or treatments; focus on gene discovery; or address any of the unmet needs of DC/TBD patients. This grant is made possible by Team Josh & the DCO Riders and Dyskeratosis Congenita Outreach, Inc.

11) Fibrous Dysplasia/McCune Albright Syndrome: One $74,000 grant available. FD/MAS is a rare disease caused by somatic mutations in GNAS. The mutation results in constitutive activation of the signaling protein, Gs alpha, and downstream cAMP signaling. Skeletal manifestations include bone pain, fractures, and osteomalacia/rickets. Extraskeletal manifestations include precocious puberty, hyperthyroidism, growth hormone excess, pancreatic neoplasms, and others. The grant will be awarded to initiate or advance research and understanding of any of the manifestations of the disease or its underlying pathophysiology. The research could involve understanding the mechanism and/or treatment of FD-related bone pain, developing animal models of any aspect of the disease, or performing clinical investigative studies addressing any of the unmet needs in FD/MAS patients and their management. These grants are made possible by Team FD and the Fibrous Dysplasia Foundation.

12) Generalized Lymphatic Anomaly (GLA; a.k.a. lymphangiomatosis) and Gorham-Stout Disease (GSD): Two grants available. One $101,000 grant available and one $59,000 grant available for proposals focused on basic science and/or clinical research on GSD and GLA. Areas of interest include, but are not limited to, genetic analysis, biomarker identification, cell line creation and characterization, and imaging. These grants are made possible by Team LGDA, the Lymphangiomatosis & Gorham’s Disease Alliance and Team LMI and the Lymphatic Malformation Institute. 

13) Glut 1 Deficiency (Glucose Transporter Deficiency Syndrome, Glut 1DS): One $40,000 grant available.  Glut 1 DS is a rare genetic disorder caused by a mutation in the SLC2A1 gene, which regulates the glucose transporter type 1 (Glut1).  Glucose is not transported properly into the brain, leaving it starving for the energy it needs to grow & function. 

One grant will be awarded to research focused on identifying and investigating innovative research projects that involve basic research, translational studies, clinical studies, alternative treatment theory, or gene therapy relevant to Glut 1DS.  While this RFA is not restricted to a specific therapeutic modality, preference may be given to research within the gene therapy platform technology.   This grant is made possible by the generous support by friends of Team Miles for Millie. 

14) Lymphangioleiomyomatosis (LAM): Two $50,000 pilot grants available focusing on translational proposals with strong likelihood of future federal funding, that use LAM samples, models or patient data, and which have the potential to favorably impact human health will be given priority. Examples of desirable topic areas include identification of molecular targets, biomarker development, and biomarker driven small pilot trials. These grants are made possible by Team LAM Foundation Easy Breathers and the LAM Foundation.

15) Mucolipidosis Type IV (ML4): One $45,000 pilot grant available to investigators conducting research on all aspects of disease including disease pathogenesis and clinical studies. This grant is made possible by Team Cure ML4, Pedal4Paul, Climb4Carin, and the ML4 Foundation.

16) Mucopolysaccharidoses (MPS): Two $52,000 pilot grants available.  Mucopolysaccharidoses represent a broad array of diseases due to enzyme defects that lead to abnormal metabolic storage products and multi-organ pathologies.  We are seeking applications directed to treating the central nervous system manifestations of these diseases.  These grants are made possible by Team MPS, the National MPS Society and the Ryan Foundation.   

17) Niemann Pick Type C (NPC): Two $51,000 pilot grants available. Preference will be given to research projects developing new therapies for NPC, and translational research projects that improve our understanding of the biology, pathogenesis and disease state (i.e., biomarkers or functional outcome measures to assess therapeutic impact).  This grant is made possible by Team NPC, the Andrew Coppola Foundation, Jammin' for JP, Chase the Cure and iPedal4Chad.

18) Pitt Hopkins Syndrome (PTHS): Two $51,000 pilot grants available. Pitt Hopkins Syndrome is due to a deficiency in the TCF4 gene and is characterized by severe intellectual disability and developmental delay. Other symptoms include episodic hyperventilation and/or breath-holding (55%-60%), recurrent seizures/epilepsy (40%-50%), gastrointestinal issues, and distinctive facial features. The Pitt Hopkins Research Foundation would like to focus this research on finding therapeutics and a cure for this debilitating syndrome and are not interested in natural history studies at this time. These grants are made possible by Team Pitt Hopkins Pedalers with the Pitt Hopkins Research Foundation. 

19) RASopathies: One $44,000 pilot grant available. RASopathies are a group of genetic conditions caused by mutations in genes on the Ras-MAPK pathway. These conditions, including Noonan syndrome/Noonan-related conditions (NS), cardio-facio-cutaneous syndrome (CFC), Costello syndrome (CS), and Neurofibromatosis type 1 (NF1) share many clinical features, such as developmental delay, gastrointestinal difficulties, skeletal abnormalities, hematologic abnormalities, and growth delay.

This grant should be directed toward the development of a treatment or cure for the RASopathies, and must include NS, CFC, and CS. This grant is made possible by Team RASopathies Network Riders and the RASopathies Network.

20) Tay-Sachs, Sandhoff, GM-1, or Canavan Disease: One $42,000 pilot grant is available focusing on forms of Tay-Sachs, Sandhoff, GM-1, or Canavan disease. We are soliciting proposals for innovative research projects that involve basic research, translational studies or clinical studies relevant to the diseases mentioned above.  Projects may be focused on (1) pre-clinical and clinical research needs, such as clinical outcome measures, registries, animal models, or biomarkers or (2) technology approaches such as stem cells, molecular chaperones, substrate inhibitors, small molecule drug screening, gene therapy, novel drug delivery to the brain. This grant is made possible by Team NTSAD and the National Tay-Sachs & Allied Diseases Association.

21) Snyder-Robinson Syndrome: Two $53,000 grants available. Snyder-Robinson Syndrome (SRS) is a rare genetic condition resulting from a mutation of the Spermine Synthase gene (SMS).  Spermine Synthase is responsible for converting spermidine into spermine.  This enzyme conversion is the last step in the polyamine pathway in healthy individuals; deficits in spermine synthase leads to significant clinical features including intellectual disability, seizures, global developmental delay, osteoporosis, hypotonia, and a host of other medical issues.  There is a wide range of severity among individuals with SRS.  SRS is the only genetic disorder known to impair polyamine metabolism.

The Snyder-Robinson Foundation is interested in applications which will help gain a better understanding of the mechanisms by which loss of spermine synthase function causes disease, and the identification of potential treatments that may cure or improve quality of life.  A broad range of proposals will be considered, ranging from basic science to pre-clinical trials to clinical research including strategies for improving quality of life of SRS patients.  Of particular interest to us are proposals addressing treatment of the nervous and skeletal system symptoms and investigating the efficacy of antioxidants. Proposals can use human tissues including induced pluripotent stem cells, mammalian models or other innovative approaches are strongly encouraged. These grants are made possible by the Snyder-Robinson Team and the Snyder-Robinson Foundation. 


Request for Applications for New ODC Programs of Excellence

The application process for this grant program is now closed. Thank you to all those who participated. 


Genome Editing for Treatment of Rare Diseases Pilot Grant Program

The Genome Editing for Treatment of Rare Diseases Pilot Grant Program is now closed.  Thank you to all those who participated. 

Background

The Orphan Disease Center ("The Center") of the Perelman School of Medicine at the University of Pennsylvania presents this request for applications (RFA) to support research on genome editing for the treatment of rare diseases.  All individuals holding a faculty-level appointment at the University of Pennsylvania, The Wistar Institute, or Children's Hospital of Philadelphia are eligible to respond to this RFA.  Three grants will be awarded at $100,000 direct costs per grant (plus 10% indirect costs) to be used over a 1-2 year period based on your research plan. This application will use a two-step process: (1) 1-page LOI, followed by (2) an "invitation only" submission of full application (5 pages).

The technology of genome editing has the potential to have a significant impact on treatment of genetic diseases. A strategic priority of the Orphan Disease Center (ODC) is to advance genome editing for rare diseases. To this end, ODC is soliciting applications for pilot grants to support the following areas of research;

1) Applications of genome editing for the treatment of rare diseases using cell and/or animal models.

2) Improvements in the technology of genome editing directed toward ex vivo or in vivo treatments of rare diseases.

Use of genome editing as a tool to discover therapeutic targets or in the creation of animal models is NOT responsive to this RFA.

Eligibility

All individuals holding a faculty-level appointment at the University of Pennsylvania, The Wistar Institute, or Children's Hospital of Philadelphia are eligible to respond to this RFA.

To Apply

This application process is now closed. 


Improved Therapies for MPS I Pilot Grant Program

The Improved Therapies for MPS I Pilot Grant Program is now closed.  Thank you to all those who participated. 

The ODC Improved Therapies for MPS I Pilot Grant Program provides a 1-2 year grant for $150,000.00 (direct costs/year) to support research on the development of improved therapies for patients with syndromes due to MPS I including Hurler, Hurler-Scheie, and Scheie. 

Background

The goal of this RFA is to support research on the development of improved therapies for patients with syndromes due to MPS I including Hurler, Hurler-Scheie, and Scheie.  Particular emphasis will be on treatments that improve aspects of the disease, which are not adequately treated by enzyme replacement therapy such as pathology in the CNS, skeletal system, eye and heart among others, as well as on biomarker discovery that can be used in the performance of clinical trials.  It is anticipated that most grants will utilize pre-clinical and clinical models of MPS I.  However, applications will also be considered that utilize models of mucopolysaccharidoses (MPS) other than MPS I if their use is scientifically justified and the data can be applied to improved therapies for MPS I.  A premium will be placed on studies whose data could be applied across a wide range of MPS diseases including MPS I.

Research topics relevant to this RFA include the following:

1) Repurposing of existing small molecule drugs for the treatment of MPS diseases.

  • Identification of existing pharmaceuticals for treatment in MPS diseases and demonstration of efficacy in cell and animal   models of MPS.  We will consider applications that propose methods to identify existing drugs that may be useful in MPS diseases using one of many possible experimental approaches, such as in vitro screens of drug libraries, and/or in silico drug identification.  We envision this to be a two-year project in which the repurposed drug candidate is identified in the first year and tested in vitro and in vivo in the second year.  The ODC will help the applicant to identify collaborators to conduct the MPS-specific animal studies if they are not experienced in this area. 
  • Clinical evaluation of therapeutics that are either approved for, or in clinical trials for, other indications.  Support will be considered for re-purposing of these drugs if pre-clinical studies support safety and potential efficacy in models of MPS.  The grant should support aspects of translation that will accelerate the path to the clinic.  Other sources of funding will likely be necessary to support this bench-to-bedside effort.  The applicant should describe and have access to all resources necessary to complete the proposed clinical trial.

2) Studies on pathogenic mechanisms of MPS diseases that: A) are directed toward the identification of novel therapeutic targets; or B) inform more effective development of molecular, gene or cell therapies. 

3) Discovery and evaluation of potential patient biomarkers that can be used to evaluate the short-term and long-term impact of therapeutics in clinical trials.  There is especially the need to find biomarkers that will be responsive to therapies that are given in combination with enzyme replacement therapies. 

4) Novel therapeutic approaches such as gene replacement therapy, genome editing, stem cells, and mRNA transfer.  Evaluation of these novel therapies must be conducted in animal models of MPS diseases. 

Eligibility

All individuals holding a faculty-level appointment at an academic institution or a senior scientific position at a non-profit institution or foundation are eligible to respond to this RFA.

To Apply

This application process is now closed. 


2015 Million Dollar Bike Ride Grants

The 2015 Million Dollar Bike Ride Pilot Grant Program is now closed.  Thank you to all who participated.

For questions regarding this pilot grant program, please contact Samantha Charleston at scharle@mail.med.upenn.edu, or (215) 573-6822.

Research Focus Areas for Pilot Grants:

1) Adrenoleukodystrophy (ALD): Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. The adult form, known as Adrenomyeloneuropathy (AMN) develops in young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved.

One $50,000 pilot grant is available with a focus on treatments for Adrenomyeloneuropathy (AMN), the adult form of the disease. We are interested in proposals that would provide a path towards a treatment, including advancing the understanding of what can be used as endpoints when conducting an AMN trial. This grant is made possible by Team Stop ALD and the Stop ALD Foundation.

2) Bronchiolitis obliterans: Two $50,500 pilot grants available with a focus on pediatric post-infectious Bronchiolitis Obliterans. Proposals that seek to improve understanding of the pathogenic processes involved in abnormal airway remodeling following exposure to adenovirus, mycoplasma, or other viruses or bacteria, as well as those which seek to improve clinical management and outcomes will be considered responsive. Proposals that address the development of BO as a complication of Stephens-Johnson Syndrome in the context of an airway infection with mycoplasma will also be considered.  These grants are made possible by Team Bronchiolitis Obliterans and the Children’s Interstitial and Diffuse Lung Disease Foundation. 

3) Castleman Disease: One $63,000 pilot grant available.  We would like to investigate the role that genetics plays in HHV-8-negative or "idiopathic" multicentric Castleman disease (iMCD) by performing Whole Exome Sequencing or Whole Genome Sequencing on 20-25 patients with iMCD. In addition to sequencing the samples, the CDCN would like for bioinformatics to be performed and for a consent process to be developed that the CDCN will be able to use moving forward for future studies and biobanking purposes. This grant is made possible by Team Castleman Disease and the Castleman Disease Collaborative Network. 

4) CFTR Nonsense Mutations: Two $51,500 pilot grants available to initiate or advance research and understanding of a treatment or a cure that would impact the nonsense mutation 1282X in the CFTR gene. The research could include drug discovery or other strategies to restore CFTR function, including suppression of premature termination, modulation of nonsense-mediated decay and gene editing.  These grants are made possible by Team Emily’s Entourage and the Emily’s Entourage organization.  

5) Cystic Fibrosis: One $69,000 pilot grant available. Cystic fibrosis is a genetic condition affecting the lungs and digestive system. The grant will be awarded to advance research and understanding of a treatment or cure that would impact people carrying a nonsense mutation.  The research should include, but not be limited to, the R1158X gene mutation. This grant is made possible by Team Movin’ for Mallory: Cure Cystic Fibrosis! and the Movin’ for Mallory organization.

6) Congenital Hyperinsulinism (CHI): One $71,000 pilot grant available focusing on innovative, pre-clinical or clinical studies designed to improve the diagnosis, therapy, or quality of life for those affected by congenital hyperinsulinism.  This grant is made possible by Team Raring to Go for CHI, and Congenital Hyperinsulinism International.

7) Duchenne Muscular Dystrophy (DMD): One $49,000 pilot grant available.  Duchenne is due to mutations in the dystrophin gene and is characterized by progressive muscle wasting, loss of ambulation, and death, most often in early adulthood.  There has been strong engagement in developing targeted therapies for Duchenne, but it is clear that a combination therapy approach will be necessary to achieve truly disease-mitigating outcomes.  Parent Project Muscular Dystrophy solicits applications on discovery and development of new platform technologies for preclinical evaluation of synergies among drugs and/or biologics to be used as combination therapies for Duchenne.  While specific candidate therapies can and should be used to develop and validate the platform technology, the successful applicant will focus on development of an innovative testing platform that can be more generally adopted for combination therapy development. Leveraging of other resources in development and validation of the platform technology is strongly encouraged. This grant is made possible by Team Bike to End Duchenne and the Parent Project Muscular Dystrophy organization. 

8) Fibrous Dysplasia/McCune Albright Syndrome: Two $58,500 pilot grants available.  FD/MAS is a rare disease caused by somatic mutations in GNAS. The mutation results in constitutive activation of the signaling protein, Gs alpha, and downstream cAMP signaling. Skeletal manifestations include bone pain, fractures, and osteomalacia/rickets.  Extraskeletal manifestations include precocious puberty, hyperthyroidism, growth hormone excess, pancreatic neoplasms, and others. The grant will be awarded to initiate or advance research and understanding of any of the manifestations of the disease or its underlying pathophysiology.  The research could involve understanding the mechanism and/or treatment of FD-related bone pain, developing animal models of any aspect of the disease, or address any of the unmet needs in FD/MAS patients. These grants are made possible by Team FD and the Fibrous Dysplasia Foundation. 

9) Generalized Lymphatic Anomaly (GLA; a.k.a. lymphangiomatosis) and Gorham-Stout Disease (GSD): Two $51,000 pilot grants are available to investigators conducting research on GSD and GLA. We are interested in proposals focused on basic science and/or clinical research on GSD and GLA.

One $101,000 pilot grant is available for a project focused on imaging deep lymphatic vessels in GLA or GSD patients with thoracic involvement. These grants are made possible by Team LGDA, the Lymphangiomatosis & Gorham’s Disease Alliance and Team LMI and the Lymphatic Malformation Institute. 

10) Lymphangioleiomyomatosis (LAM): Two $50,500 pilot grants available focusing on translational proposals with strong likelihood of future federal funding, that use LAM samples, models or patient data, and which have the potential to favorably impact human health will be given priority. Examples of desirable topic areas include identification of molecular targets, biomarker development, and biomarker driven small pilot trials. These grants are made possible by Team LAM Foundation Easy Breathers and the LAM Foundation.

11) Mucolipidosis Type IV (ML4): One $53,000 pilot grant available to investigators conducting research on all aspects of disease research including disease pathogenesis, and clinical studies. This grant is made possible by Team Cure ML4 and the ML4 Foundation.

12) Mucopolysaccharidoses (MPS): Two $50,500 pilot grants available.  Mucopolysaccharidoses represent a broad array of diseases due to enzyme defects that lead to abnormal metabolic storage products and multi-organ pathologies.  We are seeking applications directed to treating the central nervous system manifestations of these diseases.  These grants are made possible by Team MPS, the National MPS Society and the Ryan Foundation.   

13) Niemann Pick Type C (NPC): Two $53,500 pilot grants available. Preference will be given to research projects developing new therapies for NPC, and translational research projects that improve our understanding of the biology, pathogenesis and disease state (i.e., biomarkers or functional outcome measures to assess therapeutic impact).  This grant is made possible by Team NPC, the Andrew Coppola Foundation, Chase the Cure and iPedal4Chad.

14) Pitt Hopkins Syndrome (PTHS): Two $50,000 pilot grants available. Pitt Hopkins Syndrome is due to a deficiency in the TCF4 gene and is characterized by severe intellectual disability and developmental delay. Other symptoms include episodic hyperventilation and/or breath-holding (55%-60%), recurrent seizures/epilepsy (40%-50%), gastrointestinal issues, and distinctive facial features. The Pitt Hopkins Research Foundation would like to focus this research on finding therapeutics and a cure for this debilitating syndrome and are not interested in natural history studies at this time. These grants are made possible by Team Pitt Hopkins Pedalers with the Pitt Hopkins Research Foundation. 

15) RASopathies: One $53,000 pilot grant available. RASopathies are a group of genetic conditions caused by mutations in genes on the Ras-MAPK pathway. These conditions, including Noonan syndrome/Noonan-related conditions (NS), cardio-facio-cutaneous syndrome (CFC), Costello syndrome (CS), and Neurofibromatosis type 1 (NF1) share many clinical features, such as developmental delay, gastrointestinal difficulties, skeletal abnormalities, hematologic abnormalities, and growth delay. 

There are numerous anecdotal reports of individuals with a RASopathy having significant pain in various joints and parts of the body; however, this has not been formally addressed.

This grant will be awarded to initiate or advance research in further understanding of the pertinent clinical features that impact all three conditions (NS, CFC, and CS).  The research should include, but would not be limited to identifying the etiology, incidence, assessment, and management of pain in individuals with a RASopathy. This grant is made possible by Team RASopathies Network Riders and the RASopathies Network.

16) Tay-Sachs & Allied Diseases (TSAD): One $43,000 pilot grant available focusing on the diseases that fall under the purview of the National Tay-Sachs & Allied Diseases Association (NTSAD) and include the different forms of Tay-Sachs, Sandhoff, GM-1, or Canavan. We are soliciting proposals for innovative research projects that involve basic research, translational studies or clinical studies relevant to the diseases mentioned above.  Projects may be focused on (1) technology approaches such as stem cells, molecular chaperones, substrate inhibitors, small molecule drug screening, gene therapy, novel drug delivery to the brain or on (2) other pre-clinical and clinical research needs, such as clinical outcome measures, registries, animal models, or biomarkers. This grant is made possible by Team NTSAD and the National Tay-Sachs and Allied Diseases Association.

17) Urea Cycle Disorders (UCD): One $43,000 pilot grant available for research directed to the treatment or cure of Urea Cycle Disorders. This RFA is not restricted to a specific therapeutic modality. Preference will be given to approaches that can be leveraged across the entire spectrum of UCDs.


 Orphan Disease Center and High-Throughput Screening Core Pilot Grant

The Orphan Disease Center, in collaboration with the University of Pennsylvania's new High-Throughput Screening Core introduced a Pilot Grant Program to highlight the expertise and service of the Core available to ODC members. Applications with a focus to utilize the Core's ability to screen either a) FDA approved/FDA-like drug libraries or b) siRNA libraries of Gene Ontology (GO) categories or user-defined gene sets to identify/validate candidate gene targets were encouraged.  Awards have been granted, and this program is now closed.

High-throughput screening core: The Penn HTSC provides the Perelman School of Medicine community with HTS resources to identify genes or organic small molecule inhibitors of signaling pathways and cellular phenotypes in models of human disease. To meet the needs of investigators, the HTSC provides consultation and assistance with assay development and high-throughput screening of chemical and genetic libraries.

For any questions regarding this grant program, please contact: 
Samantha Charleston
Assistant Director
Orphan Disease Center
University of Pennsylvania
215-573-6822
scharle@mail.med.upenn.edu