Kidney Disease

Coding Dimension ID: 
300
Coding Dimension path name: 
Kidney Disease
Disease Fact Sheet Page: 
/our-progress/disease-information/kidney-disease-fact-sheet
Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-11478
Investigator: 
ICOC Funds Committed: 
$11 999 944
Disease Focus: 
Cystinosis
Kidney Disease
Kidney Failure
Metabolic Disorders
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

Autologous Human CD34+ HSC from Mobilized PBSC of Patients with Cystinosis Modified by Ex Vivo Transduction using the pCCL-CTNS Lentiviral Vector

Indication

Cystinosis - An autosomal metabolic disease that belongs to the family of the lysosomal storage disorders. Gene involved is CTNS (encodes cystinosin).

Therapeutic Mechanism

The proposed therapy intervention is intended to impact the target indication of Cystinosis via autologous tranplantation of CD34+ HSC-mediated transfer of a functional cDNA using pCCL-CTNS lentivirus vector. The gene-corrected HSC progeny will differentiate into macrophages in injured tissues and transfer cystinosin-bearing lysosomes via Tunneling Nanotubes (TNTs) to disease cells. This transfer of functional cystinosin to endogenous tissue cells leads to long-term tissue preservation.

Unmet Medical Need

The only treatment available for cystinosis is a lifetime oral cysteamine, with severe side effects and compliance challenges, that only delays the disease complications. This approach may represent a one-time life-long therapy that may prevent kidney transplantation and quality of life of patients.

Project Objective

Phase 1/2 trial completed

Major Proposed Activities

  • Clinical:
    - Screening and Enrollment
    - Product Administration
    - Clinical Monitoring/Safety Assessments by DSMB (IQVIA)
    - 24-month Patient Follow-Up
  • Manufacture clinical product for the proposed trial:
    - Mobilization and Leukapheresis
    - CD34+ Isolation & Transduction
    - Release Testing & Infusion
Statement of Benefit to California: 

California has approximately 20 cystinosis patients, and their families, who could directly benefit from this treatment. Financial burden on MediCal is expected to by reducing or eliminating the costs of Cysteamine and the treatment cost of secondary conditions such as hypothryodism, polyurea, etc (cost range per patient ~$300,000-600,0000/year). Moreover, at least 80% of the funds spent will be within the state of California.

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-11400
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$11 969 435
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

Combined hematopoietic stem cell graft and recipient T regulatory cells

Indication

Kidney disease requiring kidney transplantation

Therapeutic Mechanism

The study will determine whether patients treated with TLI and rATG, and given a haploidentical living donor hematopoietic progenitor cell transplant (HSCT) , along with in vitro expanded recipient Treg cells (what we term as combinatorial therapeutic cell therapy) can achieve sustained donor mixed chimerism and be withdrawn from immunosuppressive drugs while maintaining normal renal function after renal transplantation.

Unmet Medical Need

The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off IS drugs will improve due to reduction in side effects associated with IS drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.

Project Objective

Phase 1 trial completed

Major Proposed Activities

  • Assessment and adjustment of the Treg dose required to sustain chimerism in the recipients without causing adverse reactions such as GVHD
  • Assessing the impact of immunosuppressive drug dose reductions toward withdrawal without graft rejection or adversely affecting kidney function
  • Assess kidney duration post-transplant compared to patients undergoing SOC kidney transplants w/out cell therapy to induce immune tolerance
Statement of Benefit to California: 

A reduction or elimination of chronic rejection could have significant effects in improving transplant outcomes and significantly reducing the pool needing re-transplantation. In addition to the improved health outcomes, it is expected that the long term financial burden on patients will be reduced since the cost of IS drugs is about $15,000 to $20,000 per year. The latter costs also lead to non-compliance with medications that increases the incidence of rejection and graft loss

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-10411
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$18 763 585
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Cell Line Generation: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

MDR-101 is cellular therapy consisting of kidney donor-derived CD34+ HSCs and CD3+ T-cells.

Indication

Maintenance of kidney allograft function after withdrawal of post-transplant immunosuppressant (IS) drugs in HLA matched kidney transplants recipients

Therapeutic Mechanism

Following infusion and engraftment of MDR-101, the progeny cells establish a state of mixed lympo-hematopoetic chimerism. This leads to a condition known as immune tolerance in which the transplanted kidney is no longer viewed as foreign by the recipient. This allows the gradual withdrawal of all immunosuppressive (IS) drugs that were previously required to prevent rejection of the transplanted kidney

Unmet Medical Need

It is well established the current IS drugs are directly nephrotoxic and have increased risks of diabetes, heart disease, and cancers and contribute to increased transplant recipient morbidity and mortality and coincident transplant organ loss. Elimination of IS drugs should minimize these risks.

Project Objective

Completion of P3 study and BLA submission to FDA

Major Proposed Activities

  • cGMP manufacturing of MDR-101 product
  • Demonstrate predictive value of donor mixed chimerism testing in recipients of HLA matched HSCs
  • Demonstrate the ability to achieve durable immune tolerance
Statement of Benefit to California: 

The proposed Phase 3 clinical study, will include several clinical sites within California, the state with more kidney transplants in 2016 than any other state. If successful, this clinical study, will lead to commercial availability of this therapy, which would improve the health status of California residents who have received an HLA-matched, living donor kidney transplants. The MDR-101 product is intended to eliminate the life long need for immunosuppressive drugs and known side effects.

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-09439
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$6 653 266
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

blood stem cells and T cells from organ transplant donors will be studied under this proposal to prevent rejection of kidney transplants

Indication

to withdraw immunosuppressant drugs from kidney transplant recipients

Therapeutic Mechanism

Injection of the donor blood stem cells into recipients will prevent recipient immune cells from rejecting the donor kidney transplant.

Unmet Medical Need

The proposed treatment eliminates the life long need of immunosuppressive drugs to prevent kidney transplant rejection. Immunosuppresive drugs increase the risks of cancer, infection, and heart disease.

Project Objective

Phase 1 trial completed

Major Proposed Activities

  • Manufacture of the optimum donor cell product for injection into kidney transplant recipients
  • Assess the clinical safety of the donor cell injection
  • Assess the ability of the donor cell injection to eliminate the need for life long immunosuppressive drugs
Statement of Benefit to California: 

The proposed research is designed to improve the health status of California citizens who have received kidney transplants. Transplant recipients currently need life long immunosuppressive drugs to prevent transplant rejection. Elimination of these drugs using donor blood stem cell injections will eliminate the need for these drugs and their attendant side effects and financial costs.

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-08938
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$9 999 528
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

Human Acellular Vessel (HAV)

Indication

Conduit for Vascular Access for Hemodialysis

Therapeutic Mechanism

Mechanism of action: the HAV is comprised of intact extracellular matrix constructed by human smooth muscle cells (SMC) in a biomimetic bioreactor system. The manufacturing process is designed to create a biologic matrix similar in protein composition and 3 dimensional structure with biomechanical properties that are observed with native tissue. Once implanted, the HAV is remodeled by the host resulting in a vascular structure more similar in histological appearance to native vascular tissue.

Unmet Medical Need

Current vascular access technologies for hemodialysis are fraught with complications associated with thrombosis, infection and abandonment. Compared to conventional vascular access treatments for dialysis the HAV has the potential for less frequent clotting, abandonment and infection.

Project Objective

Completion of Phase III Clinical Program

Major Proposed Activities

  • Manufacturing & Distribution of the HAV for clinical testing in dialysis patients
  • Enrollment in Phase III Clinical Trial and Implantation of HAV into patients requiring vascular access for hemodialysis
  • Longitudinal test subject follow-up, data collection and analysis, regulatory approval of HAV for widespread clinical use
Statement of Benefit to California: 

The research proposed in this application will directly benefit California citizens by advancing medical/surgical therapies in the area of vascular access for hemodialysis. Further, through this clinical program widespread clinical experience will be developed with the HAV for a broader application of vascular reconstruction in all anatomic areas. Finally, this work will economically benefit citizens in California by pursuing clinical research activities and manufacturing processes within CA.

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-09688
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$14 082 865
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

Human Acellular Vessel (HAV)

Indication

Conduit for Vascular Access for Hemodialysis

Therapeutic Mechanism

Mechanism of action: the HAV is comprised of intact extracellular matrix constructed by human smooth muscle cells (SMC) in a biomimetic bioreactor system. The manufacturing process is designed to create a biologic matrix similar in protein composition and 3 dimensional structure with biomechanical properties that are observed with native tissue. Once implanted, the HAV is remodeled by the host resulting in a vascular structure more similar in histological appearance to native vascular tissue.

Unmet Medical Need

Current vascular access technologies for hemodialysis are fraught with complications associated with thrombosis, infection and abandonment. Compared to conventional vascular access treatments for dialysis the HAV has the potential for less frequent clotting, abandonment and infection

Project Objective

Completion of Phase III Clinical Program

Major Proposed Activities

  • Manufacturing & Distribution of the HAV for clinical testing in dialysis patients
  • Enrollment in Phase III Clinical Trial and Implantation of HAV into patients requiring vascular access for hemodialysis
  • Longitudinal test subject follow-up, data collection and analysis, regulatory approval of HAV for widespread clinical use
Statement of Benefit to California: 

The research proposed in this application will directly benefit California citizens by advancing medical/surgical therapies in the area of vascular access for hemodialysis. Further, through this clinical program widespread clinical experience will be developed with the HAV for a broader application of vascular reconstruction in all anatomic areas. Finally, this work will economically benefit citizens in California by pursuing clinical research activities and manufacturing processes within CA.

Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-10598
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$235 800
Disease Focus: 
Kidney Disease
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

Approximately 20,000 babies are born annually with kidney disease; the long-term outcome is poor. These studies address new ways to develop mini-kidney structures for transplantation to induce repair.

Impact

~85% of people on the organ waitlist are in need of a kidney and there are insufficient donors. There is a pressing need to identify methods for repair that avoid the need for an organ transplant.

Major Proposed Activities

  • Address a way to create mini-organs in 3D using growth factors, a biodegradable scaffold, and cell differentiation techniques that recapitulate kidney development and the required cell interactions.
  • Investigate the interactions between cells that induce each other by layering components and determining if structures needed are enhanced, and in a rigorous and reproducible manner.
  • Compare in a quantitative and qualitative manner the characteristic features required such as branching in layered 3D structures and the capabilities of cells to self-organize, interact, and mature.
  • Evaluate the effects of oxygen in the culture environment in which the cells and future mini-kidneys are grown to determine if the structures are enhanced and necessary vessels form.
  • Identify a candidate kidney construct with the necessary elements for future transplantation in a translational animal model of congenital kidney disease.
  • Publish the results and share outcomes on the CIRM and related websites.
Statement of Benefit to California: 

Current data on the Organ Procurement and Transplantation Network show that across the U.S. 96,986 individuals are currently awaiting a kidney and there are only 17,155 donors in 2017, to date. For the State of California, 19,525 (~85%) are in need of a kidney. Of these ~250 represent children under 17 years of age. The studies in this proposal address the urgency in identifying solutions for repair and regeneration that will benefit the State of California and the youngest citizens in need.

Grant Type: 
Research Leadership
Grant Number: 
LA1-06536
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$5 672 206
Disease Focus: 
Kidney Disease
Human Stem Cell Use: 
Embryonic Stem Cell
oldStatus: 
Active
Public Abstract: 

Kidney function is essential for removing the wastes that result from normal cell function and maintaining water and salt balance in our internal tissues. These actions are carried out by roughly a million nephrons within the kidney that filter all the body’s blood roughly once every 1-2hours. The kidney also regulates other tissues controlling blood pressure and blood cell composition, and regulating the strength of bone by activating vitamin D. Chronic kidney injury over time results in a loss of normal kidney function leading to end stage renal disease (ESRD). ESRD affects 500,000 Americans and its prevalence is increasing with a rise in diabetes and hypertension. ESRD is associated with significant morbidity and mortality: ultimately kidney transplant is the only cure but for every four patients requiring a transplant there are only enough available kidneys to help one. Life-threatening kidney injury also occurs through acute damage particularly in hospital settings were infection, toxic drugs or ischemia during surgery kills cells in the nephron shutting down the kidneys. Animal studies indicate that the kidney is unable to make new nephrons: the full complement of nephrons for live are established prior to birth. However, the damaged nephron has a limited capacity to restore activity through the regeneration of missing cells by their surviving neighbors.

Kidney stem cells give rise to all specialist parts of the complex nephron structure during kidney development. New genetic approaches in the mouse have enabled the isolation of these stems cell providing an opportunity to develop strategies to propagate and differentiate kidney stem cells into nephrons in the tissue culture dish. We expect that the insights gained from these studies will facilitate the translation of de novo nephrogenesis to human nephron cultures, and as a result, the development of new approaches to study and treat kidney disease. An alternative approach comes from the observation of limited self-repair by cells within damaged nephrons. The molecular and cellular processes at play in the damage-repair responses are largely unknown but elucidating these mechanisms will facilitate development of novel strategies to either augment the repair process following damage or prevent tubule damage in the first instance within at risk patients. Mouse models again provide a way forward to this long-term goal. By isolating repairing cells, and comparing gene expression signatures amongst damaged, repairing and healthy cells, we will identify repair specific responses and test the ability of candidate repair regulators to enhance the restoration of kidney function.

Statement of Benefit to California: 

Approximately 1% of Medicare enrollees in the State of California have End State Renal Disease and this number will rise. There is no effective cure aside from kidney transplantation, too few donors, and a high morbidity and mortality associated with long-term dialysis. Approximately 5-7% of hospitalized patients experience acute kidney injury, a leading cause of mortality in institutionalized settings. The target of kidney injury and disease is the nephron, all nephrons form during fetal life and self-repair within nephrons is thought to restore normal function. Through identifying conditions that support stem cells capable of new nephrogenesis and generating new nephrons from these cells, we will be able to explore approaches to restoring kidney function that are not currently possible. Further, the identification of factors associated with normal nephron repair will enable functional investigation of their potential clinical significance in kidney injury models. Given the fiscal cost of kidney disease within the State, the toll of kidney disease on patients and their families, and the lack of alternatives – developing approaches that treat disease would have a significant impact.

Grant Type: 
Comprehensive Grant
Grant Number: 
RC1-00144
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$2 257 040
Disease Focus: 
Kidney Disease
Human Stem Cell Use: 
Embryonic Stem Cell
oldStatus: 
Closed
Public Abstract: 

The derivation and culture of human embryonic stem cells has provided new possibilities for treatment of a wide variety of human diseases because these cells have the potential to help regenerate and repair many types of damaged tissue. Diseases for which such cell-based treatments may be helpful include obstructive renal disease, a disorder for which there has been little progress made in terms of treatment. Infants with this and other inherited kidney disease may be severely compromised before birth and treatments necessary to prolong their life may be accompanied by severe side effects. This raises many difficulties not only for these young patients but also for their families. If new ways to treat these infants prior to birth can be developed, this could lead to the delivery of healthy babies at full term. The use of cells obtained from human embryonic stem cells to repair and treat damaged kidneys prior to birth offers promise to improve survival and quality of life for these babies. Since it is clear that embryonic stem cells have vast potential to form a variety of cell types, it is possible that the kinds of cells needed to provide repair could be obtained and treatments initiated prior to birth. The studies proposed will assess ways to obtain such cells and the effectiveness of such treatments. Ultimately, even small improvements in function of damaged kidneys following embryonic stem cell-based therapies may increase survival and eliminate the need for dialysis or kidney transplants. Although methods to grow embryonic stem cells and even obtain cells that could be useful for treating some human diseases have been described, the use of these cells for human therapies remains highly controversial because their safety remains untested. While these cells have great potential and promise to form cell types useful for treatment of disease, they also have the potential for uncontrolled growth and to form tissues that would be harmful. Therefore, studies must be performed and techniques must be developed to carefully examine the use of these cells in relevant models of human disease, and before they are ever considered for human treatments. The overall intent of these studies is to develop techniques that can be used to test the safety of human embryonic stem cell-based therapies, and to determine ways to evaluate the cells after they have been injected into the body. As we develop new treatments for obstructive kidney disease, we will use this model system to explore these essential safety questions related to stem cell therapies. The studies proposed will fill a critical need for new treatments for kidney disease, ways to monitor cells in patients, and develop methods to assess safety issues associated with the transfer of this research to human patients.

Statement of Benefit to California: 

This proposal focuses on ways to fill the significant gap in the development of new human therapies using stem cells – transfer of ideas and techniques that are developed in laboratories to effective and safe treatments for human patients afflicted with disease. While the potential medical benefits of human embryonic stem cells may seem great, proof that these cells will not cause harm must be shown, and this must be accomplished before any patients receive treatments. Removing the barrier preventing the transfer of promising stem cell therapies to human patients will require connecting people with the expertise to develop and to evaluate such treatments. With this in mind, our studies will bring together collaborators from many areas: developmental biologists, clinicians, engineers, and those with vast experience in the study of stem cells and with preclinical models to address questions associated with a pediatric kidney disease, which is one of the leading causes of chronic renal failure in children. Kidney disease is a major cause of illness and death among infants and children with over 20,000 babies born each year with kidney problems. Approximately 5,000 have kidney failure and are on dialysis or are in need of a kidney transplant. In California alone, nearly 100 children under 10 years of age are currently awaiting available kidneys for organ transplant. The benefit to the California community is, thus, potential new therapies for the treatment of kidney disease in children, and a model system available to all researchers in which safety and efficacy of embryonic stem cell therapies can be predicted.