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Developing Cures

In 2011 NYSTEM issued an RFA for Consortia to Accelerate the Therapeutic Applications of Stem Cells for prevention and/or treatment of disease. The RFA called for proposals for specific disease-focused, health outcome-based, multi-disciplinary collaborative research projects that demonstrated the feasibility of proceeding to clinical application during the period of funding. Three "Consortia" awards were issued in response to this RFA and commenced March 1, 2013. A second RFA was issued in November 2013 to fund up to two additional Consortia. Below are descriptions of the funded Consortia, along with participating scientists and institutions. Information on Consortia funded in the second round will be posted once awards are made.

Commercialization of Valproic Acid Expanded Cord Blood Stem Cells as Allogeneic Grafts for Adults with Refractory Hematological Malignancies

  • Ronald Hoffman
  • Icahn School of Medicine at Mount Sinai
  • $8,782,529

Stem cell transplantation represents the only potential cure for most patients with blood cancers that are refractory to chemotherapy, as well as patients with genetic disorders that involve blood cells (sickle cell anemia, thalassemia). Only 30% of patients who require a stem cell transplant will have a matched sibling donor. Although there are over 20 million adult volunteer unrelated donors in the National Marrow Donor Program and affiliated registries, many patients, especially individuals of diverse racial/ethnic backgrounds, will not have a donor identified. An alternate source of transplantable stem cells is umbilical cord blood (CB) that is present within the placenta of every child born. There are limited numbers of stem cells within CB collections, which leads to their being useful for children but unfortunately having limited use for adults. We developed a process to expand in the laboratory the number of stem cells within a single CB collection so as to allow safe transplant into adult patients. By treating CB-CD34+ cells in a serum free culture system containing a combination of cytokines and a histone deacetylase inhibitor, valproic acid (VPA), we have been able to increase 35-fold the number of stem cells. In this proposal we will move this approach from the research laboratory to the clinic, which will allow adults who are transplant candidates without an appropriate stem cell donor to receive such expanded grafts.  Hopefully, this will provide them with a chance for a cure of their blood disorder.

 

Consortium Members

Investigator

Role

Icahn School of Medicine at Mount Sinai

Ronald Hoffman
Camelia Iancu-Rubin
Nina Bhardwaj
Marcia Meseck
Ian McNiece
Jeffrey Jhang
Alla Keyzner
John Levine
Christoph Schaniel
Umut Ozbek
Bartek Jablonski

PI
Co-PI
Collaborator
Collaborator
Consultant
Consultant
Collaborator
Collaborator
Collaborator
Collaborator
Project Leader

AllCells, LLC

Jay Tong

Co-I

Developing a Human ES Cell Derived Dopamine Neuron Source for Cell Therapy in Parkinson's Disease

  • Lorenz Studer, M.D.
  • Sloan-Kettering Institute for Cancer Research
  • $14,904,226

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is estimated to affect 4.1-4.6 million patients world-wide, a number predicted to more than double by 2030. A fundamental characteristic of PD is progressive, severe and irreversible loss of specific dopamine-producing neurons in the midbrain, ultimately resulting in disabling motor dysfunction. Multiple therapies have been developed for PD but none can restore the function of the lost cells. Cell transplantation has been considered a promising therapy but it has been plagued by multiple challenges including the absence of an appropriate cell source. Our team has developed highly efficient strategies to obtain dopamine neurons from human embryonic stem cells. In recent publications, we demonstrated that these cells can survive in rodents and monkeys suffering from Parkinsonism and can reverse motor symptoms of the disease. In addition, they have an excellent safety profile with no evidence of tumor or excessive growth in any of the animals tested. Here we propose a multidisciplinary consortium with the overarching goal of developing an optimized, clinical-grade source of human DA neurons for cell therapy in PD. We anticipate that by the end of the project period, we will be ready to submit for FDA approval of a safety trial in Parkinson patients. We have assembled an outstanding group of scientists, neurologists, surgeons, industry leaders, ethicists, trial experts and patient advocates who will dedicate their efforts towards the achievement of this goal. Visit the Consortium's website here.

 

Consortium Members

Investigator

Role

Sloan-Kettering Institute

Lorenz Studer
Viviane Tabar 
Isabelle Riviere 
Urs Rutishauser
Mark Tomishima

PI
Co-PI
Co-I
Co-I
Co-I
Co-I

Weill Cornell Medical College

Claire Henchcliffe

Co-I

Northwestern University

D. James Surmeir

Co-I

Rush University Medical Center

Jeffrey Kordower
Dustin Wakeman

Co-I
Co-I

 

 

Oligodendrocyte Progenitor Cell Delivery for Restoration of Function in Multiple Sclerosis: Development of a New York Consortium for the Treatment of Myelin Disease

  • Burk Jubelt, M.D.
  • Upstate Medical University - SUNY
  • $12,126,645

Myelin is the insulation around nerves that is damaged in the nervous system of Multiple Sclerosis (MS) patients. Early in the disease there are recurrent attacks of neurological dysfunction followed by recovery, referred to as relapsing-remitting MS (RRMS). There are medicines to treat RRMS. However, they only decrease disease activity by 30 to 67%. Thus, a large number of patients continue to worsen. In mid to late stages of the disease slow progression occurs, referred to as secondary progressive MS (SPMS). SPMS is thought to occur because the nerve (axon) has lost its myelin and begins to die. There is no specific therapy for SPMS. It is also known that the cells that make myelin, the oligodendroglia, are destroyed by inflammation during acute attacks. We now propose to test the clinical hypothesis that immature oligodendroglia, called human oligodendroglial progenitor cells (hOPC) , will improve neurologic functions after brain transplantation.

To this end, we will address the following specific aims:

  • Validation of protocols for the molecular qualification of cells in order to get FDA approval to transplant the cells into the brains of SPMS patients.
  • To assess the dose dependent safety and tolerability of the hOPC.
  • To assess the potential efficacy of the hOPC to regrow myelin.

This proposal focuses on achieving all steps needed to initiate clinical trials of human oligodendrocyte progenitor cell grafts for the treatment of SPMS.  Thus, the development of therapy for this type of MS will have a major impact on the daily lives of these patients.

Consortium Members

Investigator

Role

Upstate Medical University - SUNY

Burk Jubelt
David Carter
Lawrence Chin
Luis Mejico

PI
Co-I
Co-I
Co-I

University of Rochester

Steven Goldman
Andrew Goodman
Stephen Dewhurst
Sven Ekholm
Karl Kieburtz
Mark Mapstone
Michael McDermott
Webster Pilcher
Martha Windrem
Jianhui Zhong

Co-PI
Co-PI
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I

University at Buffalo - SUNY

Bianca Weinstock-Guttman
Fraser Sim
Robert Zivadinov
Ralph Benedict
Murali Ramanathan
Robert Plunkett

Co-PI
Co-I
Co-I
Co-I
Co-I
Co-I

 

Programing Hematopoetic Stem Cells for Long-Term Targeted T Cell Therapy of Patients with Relapsed Ovarian Cancer

  • Kunle Odunsi
  • Roswell Park Cancer Institute
  • $11,922,885

The goal of our studies is to harness the immune system for improving the outcome of patients with ovarian cancer. While the majority of women with advanced stage ovarian cancer respond to surgery and first-line chemotherapy, most of these responses are not durable and more than 70% of patients die of chemo-resistant disease within 5 years of diagnosis. There is an unmet need for these patients because there is no effective treatment modality for them. Our previous efforts to generate immune responses against ovarian cancer by vaccination have been hampered by the relatively low magnitude and short lifespan of the anti-tumor immune cells. In preliminary studies, we have found that we can “re-engineer” billions of mature immune cells to become anti-tumor immune cells, and infuse them into patients. Unfortunately, these cells also do not persist for long, and clinical responses are transient.

In this proposal, our objective is to re-engineer adult stem cells derived from blood, and infuse them into ovarian cancer patients. Blood derived stem cells reside predominantly in the bone marrow, and when they develop in the body, they become mature blood cells that include immune cells. Recently, we have successfully re-engineered blood derived stem cells such that when they mature in the body of mice, they become anti-tumor immune cells, with ability to recognize and kill cancer cells. Our hypothesis is that this new approach is likely to provide a continuous (possibly lifelong) source of anti-cancer immune cells that will provide sustained attack against ovarian cancer. To accomplish our objective, we will start by conducting animal studies that will enable us to obtain approval from the FDA to test this new approach in patients. This will culminate in a clinical trial that combines the re-engineered adult stem cells with re-engineered mature immune cells for the treament of ovarian cancer patients.

Consortium Members

Investigator

Role

Roswell Park Cancer Institute

Kunle Odunsi
Joanne Becker
Thinle Chodon
Yeong Choi
Kevin Eng
Carmelo Gaudioso
Richard Koya
Shashikant Lele
Junko Matsuzaki
Philip McCarthy
Carl Morrison
Takemasa Tsuji
Paul Wallace
Sandra Sexton
Leslie Curtin

PI
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Co-I
Collaborator
Collaborator

The Jackson Laboratory

Leonard Schultz

Co-I

University at Buffalo

Richard Bankert
Alan Hutson

Co-I
Co-I

Retinal Stem Cell Consortium

  • Sally Temple, Ph.D.
  • Regenerative Research Foundation
  • $10,805,636

The retinal pigment epithelium (RPE) is a film of tissue in the back of the eye that is essential for vision. This RPE tissue degenerates in Age-related Macular Degeneration (AMD), which is the leading cause of blindness in the elderly. AMD effects 1 in 5  people over age 75 and there is no effective therapy for the vast majority of AMD patients. Our consortium has discovered an adult stem cell in the RPE, the retinal pigment epithelial stem cell (RPESC), that can be used to make new RPE cells in the culture dish. The RPESC can be obtained from Eye Bank donations and from a living patient’s own eye. Other research uses embryonic stem cells to replace RPE in AMD patients. The RPESC is the tissue-specific stem cell alternative, and has several advantages such as lowered tumor threat, production of highly pure and stable RPE, and the possibility of immune-matching for better graft outcome, an important consideration for the elderly.

A consortium of researchers, clinicians and experts in cell therapy has been assembled to perform the work necessary to apply to the FDA to allow a Phase 1 clinical trial using RPESC-derived RPE as a cell transplant therapy for AMD. This includes making clinical grade cells, demonstrating their functionality and performing the necessary animal testing.

Upon successful completion of the project goals, the consortium will have accelerated the RPESC towards the clinic. This work will enable a clinical trial to occur. If RPESC-based cell transplantation proves to be a valuable therapy, this will be of great benefit to AMD patients and families. Moreover, the treatment can be provided at NYS medical centers, allowing our large AMD population to access the new therapy close to home.

Consortium Members

Investigator

Role

Regenerative Research Foundation

Sally Temple
Jeffrey Stern

PI
Co-PI

WM Burke Medical Research Institute

Glen Prusky

Co-I

Fordham University

Silvia Finnemann

Co-I

Icahn School of Medicine at Mount Sinai

Timothy Blenkinsop

Co-I

University of Rochester

Stephen Dewhurst

Co-I

 

Vascular Niche Platform to Expand Hematopoietic Stem and Progenitor Cells Engineered to Cure Sickle Cell Disease

  • Shahin Rafii
  • Weill Cornell Medical College
  • $15,717,575

The only stem cells that have been successfully used to cure human diseases are those that make blood cells. Indeed, blood stem cells can be transferred, or transplanted, from healthy people to cure patients with blood cancers and inherited diseases like sickle cell anemia. But some patients, especially those from ethnic minorities, cannot find suitable stem cell donors. Umbilical cord blood from healthy newborns is normally discarded but it can be used to transplant such patients. The problem is that there are often too few cells in cord blood to transplant. Patients with sickle cell anemia do not get transplants very often because they get too sick when transplanted with blood stem cells from other people. We have made new laboratory discoveries that could fix these problems. We have found that cells from the inner lining of blood vessels (endothelial cells) allow blood stem cells to grow (or expand) outside the body. It has taken us more than 20 years to understand how the endothelial cells work to support blood stem cell growth. We are now ready to use these cells to treat and cure human blood diseases.  We propose to use an endothelial cell factory to expand blood stem cells and provide a chance to cure patients whose only hope for survival is healthy blood stem cells. We will use this system to expand cord blood stem cells in order to safely transplant patients with leukemia, and fix and grow the blood stem cells from patients with sickle cell anemia so that they can use their own cells for cures. If successful, these new therapies will greatly reduce the suffering of patients with blood cancers and sickle cell anemia. In the future, this approach could also be applied to other blood diseases and could revolutionize this field of medicine.

Consortium Members

Investigator

Role

Weill Cornell Medical College

Shahin Rafii
Joseph Scandura
Jason Butler
Todd Evans

PI
Co-PI
Co-I
Co-I

Memorial Sloan Kettering Cancer Center

Michel Sadelain
Isabelle Rivière
Juliet Barker
Farid Boulad
Sergio Giralt

Co-PI
Co-PI
Co-I
Co-I
Co-I

Fred Hutchinson Cancer Research Center

Hans-Peter Keim

Collaborator