Research Priority Areas

JDRF Research Strategy, Priorities, and Funding Opportunities
Fiscal Year 2015 (July 1, 2014 – June 30, 2015)

Table of Contents

JDRF’s Vision

JDRF is focused on funding and catalyzing research that will lead to a cure of T1D, improving the quality of life and relieving the burden for people living with T1D, and preventing the disease (For more details, see Diabetes 2012; 61:30). JDRF’s focus and funding spans from early exploratory research and preclinical proof-of-principle to proof-of-concept clinical trials through to ensuring regulatory approval and reimbursement across all stages of T1D, while addressing the breadth of challenges in the discovery, development, and delivery of drugs and devices to cure, better treat, and prevent T1D. The Foundation is committed to creating a diversified pipeline of therapeutic candidates at different stages of development to maximize opportunities for success and account for attrition in the R&D process. The earliest stages of the pipeline for several T1D therapies will need to be catalyzed for the foreseeable future with identification of new disease relevant targets and pathways, and there remains a critical need for increased understanding of human T1D disease mechanisms, pathophysiology, and heterogeneity. At the same time, JDRF is focused on progressing more mature opportunities through the pipeline as quickly as possible to deliver both clinically-meaningful benefits and progressive advances on the path to a cure of T1D in the relatively near-term. Breakthrough research, transformative therapies, emerging technologies, translational opportunities, and proof-of-concept clinical trials are prioritized. JDRF partners with the academic sector, other funders and foundations, industry, regulatory agencies, and payers on a world-wide basis and is currently funding research in academia in 18 different countries and has partnered with over 40 different companies in the last decade. Success for JDRF is defined ultimately by the availability of new therapies and devices that we help bring to individuals with T1D or those at risk of developing the disease. Thus, JDRF allocates resources to ensure continuous clinical impact and therapeutic advancements for the largest number of individuals with T1D in the shortest period of time by funding programs ranging from those that are relatively close to the clinic to those that are early in discovery phases and represent potential for significant advancement and impact in longer timeframes.

JDRF’s General Therapeutic Goals

In type 1 diabetes (T1D), the beta cells in the islets of Langerhans of the pancreas have been destroyed or are non-functional, resulting in a life-time requirement of insulin replacement. Insulin is not a cure for the disease, however, and as used today, is not a guarantee against developing the chronic and devastating complications of kidney failure, blindness, nerve damage, amputation, heart attack and stroke.

To cure T1D will require inducing insulin independence in established disease by restoring functional beta cell mass by either activation of endogenous regeneration of beta cells or exogenous replacement by implantation of a source of glucose-responsive, insulin-secreting cells. Restoration of functional beta cells either by regeneration or replacement will need to be coupled with the prevention of their immune-mediated destruction. For replacement, encapsulation to thwart immune rejection of a replenishable islet or beta cell source is a top JDRF priority. In the case of regenerating beta cells, JDRF is focused on generating new beta cells by stimulating proliferation of residual beta cells, inducing generation of beta cells from precursor cells or alternative mature cells such as alpha cells of the islets, or inducing redifferentiation of dedifferentiated beta cells, and maintaining the survival of extant and newly generated beta cells. At the same time, the immune-mediated destruction of new beta cells must be prevented. The development of beta cell autoantigen specific immunotherapies to induce stable durable immunoregulation is a key JDRF priority.

Until a cure is at hand, JDRF is committed to keeping individuals with T1D healthy and to reducing the daily burden of living with the disease by developing and delivering better options for managing T1D. Improving lives today and preventing diabetic complications in the future requires improving glucose control with devices, including development of closed loop artificial pancreas systems, and with drugs and biologics, including repurposing of existing ones. A subset of individuals with established T1D may gain clinical benefit by increasing the function of their own residual beta cells through various interventions. This is an area of high interest to JDRF and requires further exploration. In recent onset T1D, residual beta cells are usually present and JDRF is focused on enhancing their survival and restoring and maintaining their function with agents targeting beta cell stress and survival and redifferentiation, inflammation, autoimmunity, and glucose control with a long-term goal of inducing durable insulin independence.

As part of its overall strategy, JDRF is also focused on prevention of T1D, representing prevention of symptomatic T1D and long-term insulin dependence JDRF is funding research to further understand the pathogenesis of human T1D and to develop and test interventions to prevent the onset of insulin dependence. Both primary prevention (prevention of beta cell autoimmunity) and secondary prevention (prevention of the onset of symptomatic T1D in at-risk individuals) of T1D are being targeted.

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SUMMARY OF PLANNED RFAs (REQUEST FOR APPLICATIONS)

JDRF is planning to solicit proposals over the next 18 months in the following areas that address the priority research areas:

  • JDRF Encapsulation Consortium: Developing and Testing Novel Encapsulation Technologies
  • Clinical Trials to Preserve Beta Cell Function and Delay Onset of Symptomatic Disease in the At-risk Setting for Type 1 Diabetes (T1D)
  • Diabetic Retinopathy Biomarker Discovery and Validation
  • Exploratory Clinical Trials for Diabetic Retinopathy
  • Diabetic Nephropathy Biomarker Discovery and Validation Using Type 1 Diabetes Cohorts
  • Exploratory Clinical Trials to Prevent Progression of Diabetic Nephropathy
  • Combination Therapies in Type 1 Diabetes (T1D)
  • Glucose-Responsive Insulin Discovery and Validation
  • Exploratory Clinical Trials of Non-Insulin Adjunct Therapies in Type 1 Diabetes
  • Targeting Islet Cell Plasticity for Regeneration of Beta Cell Function in T1D
  • Optimizing Therapeutic Strategies for Human Pancreatic Beta Cell Regeneration
  • International TrialNet Clinical Centers
  • Small Molecule Screens for Beta Cell Regeneration and Survival (JDRF-Calibr Partnership)
  • Novel Approaches to Antigen Specific Immunotherapy (ASI) and Small Mechanistic Trials of ASI
  • Autoimmune Memory
  • T1D Biomarkers
  • Pathogenesis and Heterogeneity of Human T1D

For more information on specific RFAs please visit the JDRF website.
There are multiple funding mechanisms available for Academia and Industry that will be applied to these opportunities as described in the specific RFAs. Please consult the JDRF website for the details of the RFA and the application process.

Funding decisions for research proposals submitted in FY2015 will be based on the priorities outlined in the RFA and in this document.

Important Notes:

  • Applicants seeking funding support for research are reminded that the JDRF research program is intended to complement, and not to replace, funding available from national or international research funding organizations, including the European Commission, or the US National Institutes of Health.
  • JDRF advocacy efforts were substantial in establishing research resources such as the International Type 1 Diabetes Genetics Consortium (www.t1dgc.org), the Type 1 Diabetes TrialNet (www.diabetestrialnet.org), the Immune Tolerance Network (ITN) (www.immunetolerance.org), and the Autoimmune Disease Prevention Centers. JDRF welcomes the participation of all investigators in accessing their available expertise and resources.
  • Investigators with research proposals in priority areas are encouraged to contact the identified JDRF lead scientists to discuss the best options for funding and alignment with JDRF priorities. All applications proposing clinical research must receive direct permission from the JDRF program scientific lead before submitting a proposal. Each clinical application is expected to follow the JDRF Guidelines for Clinical Investigations on the JDRF website.
  • Applicants are encouraged to review JDRF’s Intellectual Property (IP) policy prior to applying for funding (http://jdrf.org/grant-center/information-for-awardees/grants-policies-and-procedures/). JDRF’s IP policy contained within an award’s terms and conditions is non-negotiable. Acceptance of the IP policy by the Grantee Institution’s authorized signing official is a requirement to activate an award. For domestic grantees, to the extent that a Grantee Institution is required under a US state law other than that of New York to be subject to the laws of that state, and such state laws are in conflict with any provisions within JDRF’s IP policy, modifications or waivers to the policy will be limited to the extent that the laws applicable to the Grantee Institution are inconsistent with the provisions. For international grantees, to the extent that a Grantee Institution is required under a foreign State law to be subject to the laws of that governing body, and such State laws are in conflict with any provisions within JDRF’s IP policy, modifications or waivers to the policy will be limited to the extent that the foreign State laws applicable to the Grantee Institution are inconsistent with the provisions.

An amendment or waiver of any provision of the Terms and Conditions by JDRF must be in writing to be effective. Notwithstanding the foregoing provisions, nothing in JDRF’s IP policy is intended to, or should be construed to, conflict with Federal or foreign State law governing the Grantee Institution, including any Bayh-Dole or NIH/European Commission obligations that may arise with respect to Inventions resulting from research funded by both JDRF and Federal or foreign State funds. Federal or foreign State law shall govern in the event of any inconsistency with the IP policy.

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JDRF FY 2015 RESEARCH PRIORITIES

Encapsulation

Therapeutic Goal: A replenishable encapsulated beta cell product capable of delivering insulin independence for at least 1 year with no chronic immunosuppression therapy

Based on recent successes with cadaveric pancreas and islet transplantation, JDRF has shifted its emphasis from cadaveric islet transplantation towards developing replenishable alternative beta cell sources and encapsulation technologies to support and protect such cell sources. These two areas address the shortage of human cadaveric donor pancreata and the requirement for lifelong Immunosuppression that restrict the availability of current human pancreas/islet transplantion to a small group of individuals with T1D.

Progress in beta cell and stem cell biology has resulted in protocols for deriving human pancreatic endocrine cell progenitors from human embryonic stem cells (hESC). Several companies have applied this knowledge and are poised to develop hESC-derived pancreatic progenitors as potential commercial beta cell replacement products. Meanwhile, xenotransplantation using porcine islets has also advanced and is gaining acceptance as a potential readily available cell source. These advances have positioned hESC-derived cells and porcine islets as the most promising replenishable alternative sources of beta cells. As such, developing effective encapsulation approaches for immune protection of these cell sources is currently a major JDRF priority.

JDRF expects the ultimate immune protective encapsulated cell source products to evolve over a multi-stage development pathway. Each next generation product using either encapsulated hESC-derived cell products or porcine islet cells is anticipated to improve immune protection to increase durability of activity as they eliminate the burden of immunosuppression. In FY2013, JDRF established an encapsulation consortium involving academia and industry partners to accelerate the development timeline of encapsulated islets by encouraging collaborations among multi-disciplinary experts (bioengineers, chemists, immunologists, transplant researchers, etc.) and by fostering protocol standardization and independent replication of promising results. Research applications in the area of Encapsulation (except training grants) that are selected for funding will be required to participate in the JDRF Encapsulation Consortium.

JDRF Priority Areas in FY2015

  • Development of novel biomaterials and innovative encapsulation methods
  • Macro-encapsulation device development and testing with human pluripotent/embryonic stem cell-derived beta cell products that have demonstrated functional competence
  • Large animal and clinical testing of technologies that have robust pre-clinical proof-of-principle
  • Elucidation of mechanisms to improve durability and mature function of encapsulated beta cell sources
  • Modification of cells and/or associated materials to optimize local immune modulation for long-term beta cell/islet survival and function without systemic immune suppression
  • Fostering standardization, head-to-head comparison, and sharing of data and reagents

Inquiries:Albert Hwa, Ph.D. (ahwa@jdrf.org Tel: 212-479-7663)

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Beta Cell Regeneration and Survival

Therapeutic Goal: Drugs or biologics that promote the survival, health, and function of beta cells for all stages (at-risk, new onset, established) of T1D. Drugs or biologics that restore functional beta cells to achieve insulin independence in established T1D

It is now appreciated that beta cells are not passive victims in the development of T1D, but that beta cell stress with activation of the unfolded protein response (UPR) initiates loss of beta cell function and mass in T1D and conceivably triggering of or potentiating the beta cell specific autoimmune response. Beta cell survival therapies are envisioned to prevent loss of beta cell function and/or restore function of beta cells or dedifferentiated beta cells in the at-risk and new onset stages of T1D, and to preserve residual beta cell function in those individuals with established T1D with significant residual beta cell mass. It may prove possible to promote recovery of clinically significant functional beta cell mass by targeting beta cell survival and/or underlying immune-mediated beta cell destruction in individuals with residual beta cells or beta cell precursors. Preserving residual beta cell function in the recent onset T1D setting has the potential to result in clinically meaningful improved glucose control and decreased risk of hypoglycemia and long-term diabetic complications. JDRF has also prioritized the development of biomarkers of beta cell stress to aid in the development and clinical assessment of beta cell survival therapies for T1D.

Discovery and development of beta cell regenerating therapies is also a high priority to restore beta cell function and achieve insulin independence in people with established disease. To protect newly regenerated beta cells, beta cell survival therapies may also be required. Regenerating therapies include: a) therapies to promote the expansion (replication, division and growth) of residual mature beta cells; b) therapies targeting beta cell neogenesis by promoting the differentiation of an endogenous adult stem cell or precursor cell or the conversion of an alternative mature cell type, such as an islet alpha cell, into a beta cell, and c) therapies to promote expansion and then subsequent re-differentiation of dedifferentiated beta cells.

In parallel with these therapeutic objectives, JDRF has prioritized the discovery and validation of candidate biomarkers of early beta cell dysfunction to aid in the design and execution of more efficient and effective clinical studies. Biomarkers for beta cell stress, death, dysfunction, functional mass, and regeneration are potentially key tools for accelerating beta cell research. Imaging or alternative approaches for detecting/quantifying beta cell mass and function, islet inflammation, beta cell rejection, and newly generated beta cells could have a direct impact on the success of beta cell replacement and regeneration. Such tools could aid in the design and execution of more efficient and effective clinical studies and provide more specific endpoints. Likewise, the success of beta-cell specific clinical intervention strategies may be contingent upon the development of specific and safe targeting of the beta cell; innovative approaches to develop these tools and technologies are encouraged.

JDRF Priority Areas in FY2015

  • Repurposing existing drugs or biologics to promote beta cell survival and function
  • Discovery of optimal drug targets and lead compounds to safely promote human beta cell replication while maintaining beta cell health and function
  • Discovery and development of novel biologic factors to promote beta cell regeneration and survival as potential therapies
  • Discovery and validation of candidate biomarkers of beta cell stress
  • Discovery and validation of targets, mechanisms, and assays with potential to non-invasively measure beta cell mass, function, inflammation, rejection, death, and newly generated beta cells and their late-stage precursors
  • Site-targeted delivery of therapeutics to pancreatic islet endocrine cells
  • Islet-immune interactions

Inquiries: Patricia Kilian, Ph.D. (pklilan@jdrf.org) or Andrew Rakeman, Ph.D. (arakeman@jdrf.org Tel: 212-479-7664)

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Beta Cell Autoantigen-Specific Immune Therapies

Therapeutic goal: Vaccines, drugs, or biologics and combinations that induce/restore durable beta cell specific immunoregulation to preserve residual insulin-secreting cells in established, recent-onset, or at-risk stages of human type 1 diabetes and prevent immune-mediated destruction of regenerated beta cells

JDRF is actively supporting research on immunopathogenesis and immunotherapeutic intervention at each stage of type 1 diabetes- at-risk, recent onset, established. Developing autoantigen-specific therapies to promote immune tolerance/immunoregulation to beta cell antigens without generally weakening the immune system is a high priority for JDRF. Ultimately, combining antigen-specific and non-antigen specific immune approaches (e.g., anti-inflammatory and other immunomodulatory agents) may be required to durably control the autoimmune response. Developing immune prognostic and predictive biomarkers and an improved understanding of the immunopathogenesis of human type 1 diabetes, utilizing resources such as JDRF nPOD (www.jdrfnpod.org), is critical and is prioritized. Robust T1D immune biomarkers that can reliably predict risk, stage progression, stratify clinical trial subjects, and predict therapeutic responses are required for clinical development of therapies and for improved design and execution of clinical trials. Standardized assays or panels of assays that utilize small patient sample aliquots are also required.

JDRF Priority Areas in FY2015

      • Discovery and development of beta cell antigen-specific immunotherapies
      • Discovery and development of prognostic and predictive immune and inflammatory biomarkers for clinical trial subject stratification, monitoring disease progression, and predicting and evaluating responses to therapies
      • Demonstration of induction of immune tolerance with vaccines in humans
      • Immune-islet interactions
      • Evaluation of combinations of islet antigen-specific immunotherapy with immunomodulation in asymptomatic or symptomatic stages of T1D

Inquiries: Andrew Rakeman, Ph.D. (arakeman@jdrf.org Tel: 212-479-7664) or Simi Ahmed, Ph.D. (sahmed@jdrf.org or 212-479-7779)

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Prevention of Type 1 Diabetes

Therapeutic Goals: Prevention of onset of beta cell-specific autoimmunity or symptomatic disease in individuals at-risk of developing T1D

The incidence of T1D has been increasing about 3-4% annually for the last several decades and at even higher rates in the age range 1-5 years in many countries. JDRF is focused on both primary prevention (prevention of beta cell autoimmunity) and secondary prevention (prevention of symptomatic disease) of T1D. Developing childhood population-based primary and secondary prevention interventions is prioritized as are approaches to prevent T1D in relatives of affected individuals. Vaccine-based approaches (diabetes-related viral vaccines, beta cell autoantigen-specific immunoregulatory vaccines, or vaccines to augment or accelerate global immunoregulation in infancy) are prioritized for primary prevention. Secondary prevention will require cost-effective childhood population-based approaches to screen for risk and precise staging of disease progression to allow tailored, stage-specific interventions to prevent symptomatic T1D, which may include targeting: islet inflammation, beta cell-specific autoimmunity, beta cell survival, and/or dysglycemia, as detailed in the therapeutic area descriptions above. Further insights into the pathogenesis, staging, and heterogeneity of human type T1D will be required to effectively develop and deliver preventive interventions. Further insights into JDRF’s strategy for Prevention are described at: http://countdown.jdrf.org/Features.aspx?id=8589934700

JDRF Priority Areas in FY2015

  • Discovery and validation of biomarkers to monitor risk and stage progression of human type 1 diabetes in the at-risk setting
  • Demonstration whether human type 1 diabetes is a relapsing-remitting disease in the at-risk setting
  • Use of clinical biosamples from natural history studies to better characterize disease pathogenesis, heterogeneity, stages, risk scores of progression, and slow and fast progression in the at-risk setting
  • Secondary prevention clinical trials using repurposed or novel agents as well as establishment of cohorts in which to conduct such trials
  • Development of insights around microbiota-induced immunregulation or viral-induced autoimmunity relevant to prevention of human T1D

Inquiries: Jessica Dunne, Ph.D. (jdunne@jdrf.org; Tel: 212-479-7595)

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Pathogenesis and Pathophysiology of Type 1 Diabetes

Goals: Characterization of the etiopathogenesis and heterogeneity of type 1 diabetes and development of biomarkers to stage and predict progression of type 1 diabetes

Human type 1 diabetes (T1D) is heterogeneous with varying age of onset, rate of progression, preservation of residual beta cell function, metabolic imbalances, and development of diabetic complications. The etiopathogenesis of the disease(s) and its complications may also be variable. New insights into the pathophysiology and heterogeneity of T1D are required to better stage the disease, predict rate of progression, stratify subjects for clinical trials, and develop biomarkers for clinical trials. Resources such as JDRF nPOD (www.jdrfnpod.org) and biosamples from natural history and intervention T1D trials may be leveraged for these studies.

JDRF Priority Areas in FY2015

  • Biomarkers that predict rate of progression of loss of functional beta cells at all stages of T1D in children and adults
  • Mechanisms of preservation of functional beta cells in long-standing established T1D and the slow rate of loss of functional beta cell mass in some individuals with adult onset T1D
  • Presence and role of dedifferentiated beta cells in established T1D
  • Role of beta cell autoimmunity in ongoing loss of beta cell function
  • Role of pancreatic islet alpha cells in T1D

Inquiries: Andrew Rakeman, Ph.D. (arakeman@jdrf.org; Tel: 212-479-7664) or Sanjoy Dutta, Ph.D. (sdutta@jdrf.org; Tel 212-479-7668)

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Artificial Pancreas Device Systems

Therapeutic Goal: Artificial pancreas systems with increasing automation that improve/restore glucose regulation with significant reduction in HbA1c, significant reduction in hypoglycemia, and improved quality of life.

Research consistently shows that glycemic control directly impacts the risks associated with diabetes, including hypoglycemia, heart disease, kidney disease, eye disease, and peripheral nerve disease. It is well documented that elevated mean glucose is directly linked to the formation of these diabetic complications. Despite considerable progress in treatments and technology, glycemic control goals for people with T1D often remain out of reach. New technologies to measure glucose and dispense insulin have matured and the potential exists to apply new technology to enhance control, as well as to couple that technology to insulin delivery and controller algorithms to automatically regulate blood sugar levels. JDRF is committed to accelerating the development of sequential stages of automated artificial pancreas device systems.

JDRF Priority Areas in FY2015

  • Outpatient trials of prototype artificial pancreas systems
  • Automated insulin delivery systems
  • Ultra-fast insulins
  • Dual chamber pumps
  • Advanced algorithms
  • Insulin sensing technology
  • Miniaturization and handheld devices

Inquiries: Aaron Kowalski, Ph.D. (akowalski@jdrf.org; Tel: 212-479-7512), Sanjoy Dutta, Ph.D.  (sdutta@jdrf.org; Tel: 212-479-7668), or Marlon Pragnell, Ph.D. (mpragnell@jdrf.org; Tel: 212-479-7690)

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Glucose Modulating Agents

Therapeutic Goal: Drug based approaches that improve/restore glucose regulation with significant reduction in HbA1c, significant reduction in hypoglycemia, and improved quality of life.

Drug-based approaches to improve glucose control are required in T1D. Novel insulins- both faster-acting and glucose-responsive insulins- and improved delivery of insulin to more closely approximate physiologic insulin release and duration of action are prioritized. In addition to insulin, other hormonal functions are compromised or missing. Several non-insulin hormonal drug based treatments that reset the missing balance in T1D are also a priority. Finally, the repurposing of drugs for T1D that are approved or in clinical development for other diseases, or other novel therapeutics are key priorities.

It should be noted that optimal glucose regulation is also important to preserve the viability of either regenerated or transplanted beta cells and to preserve functional beta cell mass in recent onset type 1 diabetes and in the pre-diabetes stages of the disease.

JDRF Priority Areas in FY2015

  • Discovery and development of glucose-responsive insulins
  • Discovery and development of other novel hormonal drugs such as liver-targeted insulin, soluble glucagon, etc.
  • Evaluation of clinical benefits of non-insulin drugs as an adjunct to insulin to improve glucose/metabolic control
  • Repurposed or novel drugs for improved overall metabolic control
  • Combinations of therapies with complementary mechanisms of action to leverage additional benefits
  • Better characterization of clinical and metabolic heterogeneity of established type 1 diabetes with the goal of identifying appropriate therapeutic interventions for specific sub-populations within T1D

Inquiries: Sanjoy Dutta, Ph.D.  (sdutta@jdrf.org Tel: 212-479-7668), or Marlon Pragnell, Ph.D. (mpragnell@jdrf.org Tel: 212-479-7690)

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Diabetic Kidney and Eye Complications Therapies

Therapeutic Goals: Agents that prevent, arrest and reverse diabetic kidney and diabetic eye disease.

Insulin replacement therapy for type 1 diabetes is not a cure, and is often insufficient to prevent the onset of debilitating and/or life-threatening diabetic complications, including loss of vision and kidney disease, among others. Despite significant advances in glucose monitoring and insulin therapy, people with diabetes still spend significant portions of the day with hyperglycemia and fail to achieve recommended glucose control, placing them at risk for the development of diabetic complications. Unfortunately, even in the face of improved glucose control, some people progress to develop diabetes complications, possibly through genetic predisposition and other yet unidentified factors. JDRF is focused on discovering and developing therapies to prevent, arrest, or reverse diabetic complications of the eye and kidney, with a priority for intervening at earlier stages of disease progression.

JDRF Priority Areas in FY2015

  • Biomarkers predicting progression of non-proliferative diabetic retinopathy (NPDR) and predicting response to therapy
  • Target validation and proof-of-concept clinical trials in pathways to prevent vision loss in moderate to severe NPDR
  • Target validation and proof-of-concept clinical trials in pathways to delay/prevent progression of diabetic kidney disease
  • Prognostic and predictive biomarkers in diabetic kidney disease, with a priority for validation of biomarkers to accelerate clinical trials

Important Note: Although JDRF recognizes the importance of research investigating other complications of diabetes, JDRF priorities for FY2015 do not include atherosclerosis and peripheral vascular diseases, myocardial infarction and stroke, wound healing, analgesia and pain research, neuropathy, embryopathy, cognitive impairment, depression, periodontal disease and osteoporosis.

Inquiries: Helen Nickerson, Ph.D. (hnickerson@jdrf.org; Tel: 212-479-7522) and Sanjoy Dutta, Ph.D. (sdutta@jdrf.org; Tel: 212-479-7668) 

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