Neurological Disorders

Coding Dimension ID: 
303
Coding Dimension path name: 
Neurological Disorders
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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