Neurological Disorders

Coding Dimension ID: 
303
Coding Dimension path name: 
Neurological Disorders
Grant Type: 
Progression Award - Discovery Stage Research Projects
Grant Number: 
DISC2P-12212
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$180 000
Disease Focus: 
Neurological Disorders
Spinal Cord Injury
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
Statement of Benefit to California: 
Grant Type: 
Progression Award - Discovery Stage Research Projects
Grant Number: 
DISC2P-12150
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$202 667
Disease Focus: 
Neurological Disorders
Traumatic Brain Injury
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
Statement of Benefit to California: 
Grant Type: 
Progression Award - Discovery Stage Research Projects
Grant Number: 
DISC2P-11700
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$202 500
Disease Focus: 
Epilepsy
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
Statement of Benefit to California: 
Grant Type: 
Progression Award - Discovery Stage Research Projects
Grant Number: 
DISC2P-11595
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$201 150
Disease Focus: 
Neurological Disorders
Parkinson's Disease
Human Stem Cell Use: 
iPS Cell
Public Abstract: 
Statement of Benefit to California: 
Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-11628
Investigator: 
ICOC Funds Committed: 
$4 963 684
Disease Focus: 
Brain Injury, hypoxic, ischemic
Neurological Disorders
Pediatrics
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Translational Candidate

An established stable human neural stem cell line unmanipulated genetically & propagated under defined conditions

Area of Impact

Perinatal asphyxia (also called hypoxic-ischemic injury), a major untreatable cause of cerebral palsy & cognitive disability

Mechanism of Action

hNSCs rescue the penumbra, the part of the brain lesion following perinatal asphyxia that still has viable though endangered cells. Such rescue includes preserving tissue; host neuron growth; revascularization; inhibiting inflammation & scarring. Anatomic & behavioral improvement results. If strategically administered, hNSCs can supply their neuroprotective molecules in a manner that synergizes with standard-of-care, hypothermia, which is only marginally effective but must be offered to babies.

Unmet Medical Need

Perinatal hypoxic-ischemic brain injury is an untreatable common cause of CP & disability. Hypothermia (HT) is standard-of-care for this condition although it is only marginally-effective. Any new trial must include HT. We will coordinate hNSC administration to synergize with HT & improve outcome.

Project Objective

Pre-IND meeting, ultimately a Phase 1b/2a trial

Major Proposed Activities

  • Ascertain the proper timing of hNSC administration in relation to hypothermia to achieve synergy
  • Determine the manufacturing specifications & biodistribution of the hNSCs in anticipation of IND-enabling studies
  • Preparation of a pre-IND package
Statement of Benefit to California: 

Perinatal asphyxia occurs in 2-4/1000 births. Despite hyperthermia (which is only marginally effective), 80% of asphyxiated infants develop neurologic signs with 10-20% remaining significantly impaired (e.g., CP; disability; epilepsy). The cost to California economy is $1M/child in terms of lifelong medical & rehabilitative care; the impact on family dynamics is 2-5-fold greater than that. We believe stem cell-based interventions can improve these outcomes.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-11611
Investigator: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$4 848 750
Disease Focus: 
Epilepsy
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Translational Candidate

A cellular therapeutic comprised of inhibitory nerve cells produced from human stem cells

Area of Impact

Drug-resistant chronic temporal lobe epilepsy

Mechanism of Action

The product candidate is intended to be delivered into the seizure focus, integrate, and secrete the inhibitory neurotransmitter GABA to rebalance neural electrical activity in the brain and eliminate/reduce seizures.

Unmet Medical Need

The seizures in approximately one-third of epilepsy patients do not adequately respond to current anti-epileptic drugs. Alternative surgical interventions are highly invasive and damage brain tissues. The proposed product candidate is intended to be restorative and long-acting.

Project Objective

Pre-IND meeting; Pilot material manufactured

Major Proposed Activities

  • Finalize manufacturing process to be appropriate for future clinical use
  • Produce Pilot product using the intended process, confirm efficacy in two rodent models of chronic epilepsy and demonstrate safety at maximum dose
  • Select intended clinical cell delivery device and conduct preIND meeting to confirm IND-enabling preclinical requirements
Statement of Benefit to California: 

Epilepsy is the fourth most common neurological disorder affecting more than 400,000 people in the State of California. One-third of epilepsy patients are considered to be drug-resistant and have persistent, uncontrolled seizures that can be disabling and affect quality of life. Alternative surgical interventions are highly invasive and may cause lasting impairment. This proposal aims to further develop a cellular therapeutic for treating drug-resistant epilepsy.

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.

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