Neurological Disorders

Coding Dimension ID: 
303
Coding Dimension path name: 
Neurological Disorders
Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-11579
Investigator: 
ICOC Funds Committed: 
$6 235 897
Disease Focus: 
Neurological Disorders
Spinal Cord Injury
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Translational Candidate

H9 (WA09) embryonic stem cell-derived neural stem cells with a spinal cord identity (H9-NSCsc)

Area of Impact

Severe spinal cord injury

Mechanism of Action

Our candidate therapy for SCI uses human neural stem cells in a gel-like matrix containing growth factors. We aim to fill the injury site with replacement neural stem cells that can form new neural "relays" across the injury to restore function. This approach may potentially treat severe SCI by repairing injured connections, in contrast to other stem cell clinical trials for SCI that only aim to improve the function of axons that are spared by the injury.

Unmet Medical Need

20,000 Americans sustain SCI each year, and more than 300,000 live with chronic injury, extracting a huge physical, emotional and financial toll. There are no therapies to repair the spinal cord. We aim to regenerate the injured spinal cord by "splicing" neural circuits, thereby restoring function.

Project Objective

Pre-IND meeting

Major Proposed Activities

  • Generate GMP-compliant H9 ESC Master and Working cell banks (MCB, WCB), as well as GMP-compatible H9-NSCsc MCB and WCBs.
  • Rodent studies to establish proof of concept and pilot safety.
  • Develop Chemistry, Manufacturing, and Control (CMC) characterization and release assays for the candidate H9-NSCsc.
Statement of Benefit to California: 

SCI affects approximately 300,000 people in the U.S., with more than 20,000 new injuries per year. People with SCI often endure decades of severe disability, with staggering physical, emotional, and financial costs. The first year of treatment alone is $1 million for a quadriplegic patient. Better treatments are needed, and even a modest increase in functional capacity (1-2 spinal levels) can produce meaningful improvement in quality of life and cost savings for California.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-11548
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$4 833 271
Disease Focus: 
Neurological Disorders
Traumatic Brain Injury
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Translational Candidate

Shef6.1 embryonic cells will be enriched for a neural stem cell marker, CD133. These human neural stem cells (hNSCs) are designated as S6.133.hNSCs.

Area of Impact

Shef6.1 human neural stem cells will be tested as a treatment for memory & behavioral deficits resulting from traumatic brain injury (TBI).

Mechanism of Action

Traumatic brain injury (TBI) results in loss of neural tissue and chronic inflammation. Additionally, patients may have chronic cognitive and emotional deficits. S6.133.hNSCs have been shown to improve learning and memory, and reduce anxiety in rodent, via replacing lost neurons and glial cells (via cell replacement or neurogenesis), protecting the injured brain from secondary cell loss (trophic effect), and reducing neuroinflammation (via cytokines), possibly by synergic mechanisms of action.

Unmet Medical Need

TBI is a silent epidemic, affecting 230,000 Californians yearly (comparable to Alzheimer’s), and projected to cost CA $9.6 billion per year. TBI can lead to significant chronic deficits, yet there are no approved therapies, whether pharmacological or cell based, and few products in the pipeline.

Project Objective

We are targeting a Pre-IND meeting by month 30.

Major Proposed Activities

  • Generate cGMP compatible human neural stem cells (hNSCs) from Shef6.1 embryonic stem cells. Finalize CMC methods and test sterility and stability.
  • Test efficacy, safety, dose & immunosuppression in male & female Athymic nude rats, and a non-human primate model (marmoset) of traumatic brain injury
  • Finalize target product profile (TPP) and Pre-IND documents with clinical team and consultants at iQVIA; schedule Pre-IND meeting with the FDA.
Statement of Benefit to California: 

Traumatic Brain Injuries (TBI) are the leading cause of disability. Yearly, 1.7 million American’s experience a TBI (~230,000 Californians), costing California ~$9.6 billion YEARLY. A cell therapy that could reduce inflammation, replace injured brain tissue, or protect host neurons to improve learning and memory could have significant implications for a patient’s quality of life and could significantly reduce the economic impact of TBI on the patient, their family, and the state of California.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-09394
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$5 944 681
Disease Focus: 
Alzheimer's Disease
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Translational Candidate

Human iPSC-derived GABAergic interneuron progenitors.

Area of Impact

Alzheimer's disease and related conditions.

Mechanism of Action

Transplantation of human iPSC-derived GABAergic progenitors, which will develop into mature GABAergic interneurons, to replace the lost GABAergic interneurons in the hippocampus of AD brains and related disorders.

Unmet Medical Need

As a complex disease that damages the hippocampus, a brain region essential for cognition, Alzheimer's disease presents unique challenges for developing traditional therapies. iPSCs provide a way to generate brain cells for cell-replacement therapy.

Project Objective

Pre-IND

Major Proposed Activities

  • Establish a robust differentiation protocol for deriving GABAergic progenitors from human iPSCs.
  • Short-term efficacy and safety tests of human iPSC-derived GABAergic interneuron progenitors.
  • Long-term efficacy and safety tests of human iPSC-derived GABAergic interneuron progenitors.
Statement of Benefit to California: 

Alzheimer's disease (AD) is the leading cause of dementia in California. Currently, there are over 480,000 AD patients in California—more than in any other US state—costing over $20 billion USD in healthcare each year. This research project focuses on developing cell-replacement therapies for AD. Successful completion of this research could help to improve the health of Californians and reduce the adverse impact of AD, thereby increasing productivity and enhancing quality of life.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-08552
Investigator: 
ICOC Funds Committed: 
$6 349 278
Disease Focus: 
Amyotrophic Lateral Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Translational Candidate

Spinal cord injections of human embryonic stem cell (hESC)-derived allogeneic neural stem cells (heNSCs) for treatment of ALS

Area of Impact

Treatment of Amyotrophic Lateral Sclerosis (ALS)

Mechanism of Action

Although the exact molecular mechanism of action is unknown, extensive research supports the concept that the behavior of defective astrocytes is key to the death of motor neurons and the development and progression of ALS. Allogeneic neural stem cells (heNSCs) injected into the spinal cord migrate and differentiate into functional astrocytes which can protect and support endogenous neurons, preventing further motor neuron loss and disease progression.

Unmet Medical Need

ALS is a disease for which there is literally no currently effective therapy. While there are some mild palliative approaches to treatment, in virtually all cases the diagnosis of ALS is effectively equivalent to a death sentence.

Project Objective

Pre-IND meeting with the FDA

Major Proposed Activities

  • Scale up manufacturing of product for proposed studies and perform product characterization, function and efficacy testing.
  • Develop in vitro methods for testing product function, efficacy and safety.
  • Perform pilot in vivo tests for determination of cell survival, fate, safety. Develop and standardize in vivo and in vitro tumorigenicity methods.
Statement of Benefit to California: 

ALS is a disease for which there is literally no currently effective therapy. While there are some mild palliative approaches to treatment, in virtually all cases the diagnosis of ALS is effectively equivalent to a death sentence. Clearly, in view of the dire prospects facing these patients, aggressive action on multiple, parallel therapeutic fronts is critical. It is important in our view to develop an aggressive set of cell therapy programs and have multiple “shots on goal” in parallel.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-08525
Investigator: 
ICOC Funds Committed: 
$7 377 384
Disease Focus: 
Canavan Disease
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Translational Candidate

Genetically-corrected patient iPSC-derived neural progenitor cells, which have demonstrated efficacy to correct disease phenotype in a CD mouse model.

Area of Impact

This candidate has the potential to develop into a therapy for Canavan disease, a fatal neurological disease that has no cure or standard treatment.

Mechanism of Action

The proposed candidate is intended to correct disease phenotype through a cell replacement approach. Moreover, the derivative of the genetically-corrected iPSCs will provide ASPA enzymatic activity, which is deficient in Canavan disease patients. The ASPA enzyme will be able to reduce NAA level, which accumulates to a toxic level in patient brains to cause sponge degeneration.

Unmet Medical Need

There is neither cure nor a standard course of treatment for Canavan disease. The therapeutic candidate we propose to develop in this study has the potential to lead toward the development of a cell replacement therapy for this disease.

Project Objective

Pre-IND meeting and readiness for manufacturing.

Major Proposed Activities

  • Establishing a cGMP-compatible process in order to transfer the therapeutic candidate to manufacturing.
  • Determining the in vivo efficacy and safety of the therapeutic candidate prepared using the cGMP-compatible process in CD mice.
  • Preparing and conducting a pre-IND meeting with the FDA.
Statement of Benefit to California: 

California is estimated to have ~12% of all cases of Canavan disease in the U.S. Besides the emotional and physical pain this disease inflicts on families, it produces a medical and fiscal burden in California that is larger than any other states. The proposed therapeutic candidate will represent great potential for both California patients and industry. It would also help to maintain California’s leading position in clinical developments by creating safe and effective cell replacement therapy.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-08519
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$883 174
Disease Focus: 
Metabolic Disorders
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Translational Candidate

Autologous hematopoietic stem cells transduced with a lentiviral vector expressing wild type human HexA and HexB.

Area of Impact

The therapeutic candidate would halt disease progression in Tay-Sachs and Sandhoff disease patients who have no curative or ameliorating treatment.

Mechanism of Action

Wild type HexA and HexB will be delivered to affected neurons through cross correction by immune cells derived from lentivector transduced hematopoietic stem cells. This will result in a renewed degradation of accumulated GM2-gangliosides thus rescuing affected neurons and halting disease progression. The combination of gene therapy and hematopoietic stem cells offers a promising approach for constitutive and life-long delivery of HexA and B to affected neurons.

Unmet Medical Need

Tay-Sachs and Sandhoff disease are characterized by an accumulation of GM2-gangliosides due to a defective β-N-acetlyhexosaminidase protein leading to progressive, fatal neurodegeneration. There is no cure or corrective therapy for TS or SD and supportive care only marginally prolongs patient lives.

Project Objective

Our objective is to have a pre-IND meeting.

Major Proposed Activities

  • Evaluate the in vitro safety and efficacy of HexA/HexB lentivector transduced human CD34+ HPC.
  • Evaluate the safety of HexA/HexB lentivector transduced hematopoietic stem cells for engraftment, multi-lineage hematopoiesis, and tumorigenicity.
  • Evaluate the efficacy of HexA/B lentivivector transduced hematopoietic stem cells to decrease GM2 levels, increase motor function, and prolong lives.
Statement of Benefit to California: 

Tay-Sachs (TS) and Sandhoff disease (SD) are classified as rare and orphan diseases that affect patients as infants, juveniles, and adults. Currently there is no cure or effective treatment for TS or SD and supportive care can only marginally prolong the lives of patients. Our therapy would halt the progression of these diseases and after demonstrating success, would open the door for the use of hematopoietic stem cell gene therapy for the treatment of other lysosomal storage diseases.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-08471
Investigator: 
ICOC Funds Committed: 
$7 139 913
Disease Focus: 
Intestinal Disease
Metabolic Disorders
Neurological Disorders
Pediatrics
Human Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Translational Candidate

ASCENT - Advanced Superdonor Cellular Enteric Neuropathy Therapy, is a donor progenitor cell population that replaces the enteric nervous system.

Area of Impact

ASCENT would treat enteric neuropathies including Hirschsprung disease and total intestinal aganglionosis which currently have no direct therapy

Mechanism of Action

Our goal is to develop an allogeneic “off the shelf” cellular therapy to treat enteric neuropathies before surgical interventions are needed or to rescue patients in whom effects of the ENS defect persist. We propose to generate a cellular therapy from the starting material of “superdonor” human iPS cell lines. ASCENT - Advanced Superdonor Cellular Enteric Neuropathy Therapy, is a donor progenitor cell population that, after transplantation in vivo, replaces absent functional ENS components.

Unmet Medical Need

There are no direct therapies for enteric neuropathies and ASCENT would be the first cellular therapy for a broad class of severe disease including Hirschsprung disease and other enteric neuropathies that are morbid and mortal.

Project Objective

Successful Pre-IND meeting with the FDA

Major Proposed Activities

  • Manufacture ASCENT to supply the proposed studies that will assess safety and efficacy
  • Determine the optimal dosing of ASCENT as well as assess clinical safety
  • Completion of nonclinical safety studies in order to schedule and complete a Pre-IND meeting
Statement of Benefit to California: 

Enteric neuropathies cost the state of California hundreds of millions of dollars and cost the people of California more because of the severe problems including death that result from this class of diseases. This proposal benefits California in two ways: by supporting science and the industries in California that grow from ongoing investigation, but also by reducing the medical costs and suffering of patients with enteric neuropathic conditions with development of a novel and needed therapy.

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