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: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13072
Investigator: 
ICOC Funds Committed: 
$1 463 400
Disease Focus: 
Kidney Disease
Human Stem Cell Use: 
Somatic Cell
Public Abstract: 

Research Objective

AAV-SPL 2.0 is a gene therapy cure for SPLIS, a lethal childhood disorder of metabolism that causes kidney failure. Our gene therapy may also work in more common fibrotic (scarring) kidney diseases.

Impact

Our treatment may cure a rare but often fatal genetic disease (SPLIS) for which no specific treatment is available. It may additionally cure other forms of kidney disease caused by kidney scarring.

Major Proposed Activities

  • Test the ability of our gene therapy to prolong survival in a newborn mouse model of SPLIS.
  • Test the ability of our gene therapy to protect the kidney from damage in an adult mouse model of SPLIS.
  • Test the ability of our gene therapy to protect the kidney from damage in mouse models of more common forms of kidney fibrosis.
  • Use mouse models to demonstrate where in the body our gene therapy can reach and restore the activity of the enzyme encoded by the gene.
  • Test the ability of the gene therapy to restore sphingolipid metabolism in mouse models of SPLIS
Statement of Benefit to California: 

AAV-SPL 2.0 gene therapy may cure children with SPL insufficiency syndrome (SPLIS) and individuals with kidney disease arising from many common conditions and that can lead to chronic kidney disease and kidney failure. Patients with SPLIS have been diagnosed in California. Chronic kidney disease affects 3% of Californians, with higher rates in areas of agricultural work. It is more common in 65 and older adults and more common in Black and Hispanic adults compared with white and Asian adults.

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: 
Medical Device Translational Research Projects
Grant Number: 
TRAN3-13332
Investigator: 
Name: 
Type: 
PI
ICOC Funds Committed: 
$3 112 567
Disease Focus: 
Kidney Disease
Kidney Failure
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Translational Candidate

LXW7 coated ePTFE vascular graft achieves rapid endothelization and improved graft patency by capturing endogenous endothelial progenitor cells

Area of Impact

This technology will produce long-lasting vascular grafts with self-renewable “living” endothelium and improve dialysis patients’ quality of life

Mechanism of Action

The arteriovenous ePTFE dialysis graft approach is the most common form of vascular access for hemodialysis in the U.S., but has high failure rates. One of the major causes is the lack of a functional endothelium which is crucial to the prevention of thrombosis and stenosis. The LXW7 coated ePTFE graft will promote in situ endothelialization as the LXW7 works to increase the capture and binding of endogenous endothelial progenitor cells (EPCs) and endothelial cells (ECs)

Unmet Medical Need

Globally, in 2018 it was estimated that there were over 2 million people who suffered from kidney failure. Patients undergoing hemodialysis often require multiple interventions due to graft failure. There is an unmet clinical need for long-term vascular access for hemodialysis patients.

Project Objective

Pre-IDE meeting with the FDA

Major Proposed Activities

  • Manufacture, characterize, and optimize a viable prototype in making LXW7-ePTFE grafts and evaluate their properties in vitro
  • Evaluate the mechanism of action, function, and efficacy of LXW7-ePTFE grafts in small animal models
  • Investigate the short-term and long-term behavior and function of LXW7-ePTFE grafts in clinically relevant large animal models
Statement of Benefit to California: 

Californians are at risk for kidney disease. 106,888 Californians are living with end-stage renal disease (ESRD, or kidney failure). Without treatment, dialysis or a transplant, ESRD is fatal. Only 1 in 7 California patients on the waiting list got a kidney transplant in 2020. Patients undergoing hemodialysis often require multiple interventions due to graft failure. Providing a durable vascular graft with long-term patency will allow reliable access to life-saving hemodialysis for patients.

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.

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