Neurological Disorders

Coding Dimension ID: 
303
Coding Dimension path name: 
Neurological Disorders
Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-10079
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$179 911
Disease Focus: 
Alzheimer's Disease
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Research Objective

These studies will determine whether stem cell derived exosomes (nano-scale vesicles) can be used to treat the symptoms of Alzheimer’s disease (AD).

Impact

Our stem cell-derived exosome therapy will provide a viable approach to ameliorate the relentless progression of AD that severely impacts quality of life for millions of patients and their families.

Major Proposed Activities

  • Evaluate whether exosome therapy can reduce the symptoms of early stage AD including anxiety, depression, and learning and memory.
  • Evaluate whether exosome therapy can reduce the symptoms of advanced stage AD including anxiety, depression, and learning and memory.
  • Determine whether exosome therapy can slow the appearance of AD related changes typically observed in the early stage AD brain.
  • Determine whether exosome therapy can reduce the appearance of AD related changes typically observed in the advanced stage AD brain.
Statement of Benefit to California: 

In the US, California has the most cases of AD, a burden on patients, their families, and the health care system. As such, AD is an unmet medical need that requires new therapies to improve disease management. This project tests a transformational idea—human stem cell derived exosome therapy. These studies will identify a novel stem cell-based strategy and a viable approach to impede the progression of AD and it’s symptoms that severely impact quality of life for patients and their families.

Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-08825
Investigator: 
ICOC Funds Committed: 
$232 200
Disease Focus: 
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Research Objective

We found that approved anti-retroviral drugs could stop inflammation and block neurodegeneration. We propose to validate the re-purpose efficacy of these clinically-approved retroviral drugs.

Impact

We have identified an unexpected cause to a brain inflammation and a potential simple treatment. Our research could help millions of patients affected by a broad range neuro-immunological disorders.

Major Proposed Activities

  • Determine the specificity of the anti-retroviral drugs to inhibit cellular reverse transcriptase and reduce human neurodegeneration.
  • Determine the molecular mechanism responsible for the observed neuronal toxicity.
  • Determine the non-cell autonomous component of neuro-inflammation using co-culture cellular assays.
Statement of Benefit to California: 

Neuroinflammation is an important component of several neurological disorders, including autism, ALS, Parkinson, Alzheimer, lupus, multiple sclerosis and aging. These conditions affects millions of people in California and worldwide. However, little is known about what initiates such an inflammatory process. Our innovative approach is of high clinical relevance, because it suggests that patients suffering with neuroinflammation could immediately benefit from available anti-retroviral drugs.

Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-08819
Investigator: 
ICOC Funds Committed: 
$230 400
Disease Focus: 
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Research Objective

The proposed studies will develop three-dimensional cell culture methods for creating human brain neural circuits for disease research and drug discovery.

Impact

The proposed research will develop a new research platform for studying how neurons in the human brain function, how neurological disease subverts this activity, and how we might find new therapies.

Major Proposed Activities

  • Develop robust and reliable methods for creating three-dimensional organoid ("mini-brain" ) structures from human pluripotent stem cells.
  • Measure the ability of neurons within mini-brain structures to form functional connections with one another that resemble those seen in the human brain.
  • Determine how mini-brain neurons are organized at a larger network level to better model the normal and pathological activities of the human brain.
Statement of Benefit to California: 

Neurological diseases are among the most debilitating medical conditions that affect millions of Californians each year, and many more worldwide. Few effective treatments for these diseases currently exist, in part because we know very little about the mechanisms underlying these conditions. Our proposed studies will develop an innovative cell culture platform to create a facsimile of human brain circuits that will enable us to better understand disease pathologies and discover new therapies.

Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-08800
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$241 992
Disease Focus: 
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Research Objective

to develop and systematically characterize a novel model of the human BBB using a microfluidic device (chip) and cells derived from induced pluripotent stem cells (iPSCs).

Impact

The success of the proposed research will provide a novel, highly attractive model for screening of molecules to treat neurological disorders and for personalized medicine in the future

Major Proposed Activities

  • To develop a personalized model of the BBB-on-Chip using iPSC-derived brain microvascular endothelial cells (BMECs) and iPSC-derived neurons and astrocytes
  • To perform a detailed profiling of small molecules crossing (or not) the human BBB from circulating blood using Mass Spectrometry
  • To conduct a secretome profiling of peptides and proteins that are transported across the BBB with/without iPSC-derived neurons and astrocytes
Statement of Benefit to California: 

The state of California and its citizens will benefit from this project in a financial level as conducting this project at Cedars-Sinai will provide more job opportunities. Moreover, Emulate Inc. is planning to open a branch in the wet cost. Our successful collaboration will strongly promote California as their destination. Moreover, the Californian citizens will benefit from the potential development of new therapies for neurological disorders made available by this novel model

Grant Type: 
Inception - Discovery Stage Research Projects
Grant Number: 
DISC1-08723
Investigator: 
ICOC Funds Committed: 
$229 396
Disease Focus: 
Neurological Disorders
Stroke
Human Stem Cell Use: 
iPS Cell
Cell Line Generation: 
iPS Cell
Public Abstract: 

Research Objective

To determine if transplantation of iPS-interneurons cells (iPS-3i cells) enhances functional recovery in stroke.

Impact

Successful completion of the proposed studies will develop a brain repair therapy for stroke, an unmet clinical need with significant impact on society.

Major Proposed Activities

  • To determine the recovery effect of transplantation of iPS-3i cells in the mouse at subacute (7 days after stroke) and chronic (21 days) points, using measures that mimic human functional recovery.
  • To determine the integration and circuit properties of transplanted iPS-3i cells in stroke at subacute and chronic time points using anatomical and optogenetic circuit mapping.
Statement of Benefit to California: 

Stroke is the leading cause of adult disability. There is no medical therapy that promotes recovery in this disease. This research will test the effect of a new cellular transplant strategy to promote recovery in stroke, using induced pluripotent stem cells that have been differentiated into interneurons. These cells have markedly improved survival, migration and engraftment than previous stem cell approaches in stroke, and induce a form of plasticity that mimics the limited recovery in stroke.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-13059
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$5 552 611
Disease Focus: 
Neurological Disorders
Spinal Cord Injury
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Translational Candidate

The therapeutic candidate is a central nervous system tissue-derived GMP line developed under DISC2-10753 with an established GMP qualified seed bank.

Area of Impact

The target is chronic cervical spinal cord injury, which represents approximately 59% of clinical spinal cord injury cases.

Mechanism of Action

Integration of transplanted human neural stem cells is likely to direct improved locomotor function by a combination of mechanisms that include the production of new myelinating cells. Transplanted neural stem cell survival, migration, and formation of new oligodendrocytes have been linked to repair capacity.

Unmet Medical Need

There are no FDA approved treatments for spinal cord injury. There are roughly 285,000 individuals living with paralysis due to traumatic spinal cord injury in the USA, with as many as 20,425 in California at a projected collective lifetime cost of $104 billion in direct and indirect costs of care.

Project Objective

Submission of a Pre-IND and Pre-IND meeting.

Major Proposed Activities

  • Establish critical process parameters for therapeutic candidate expansion and establish GMP final product bank.
  • Complete pre-clinical testing of final product cells and conduct preliminary testing of assays for potency and comparability during cell production.
  • Test a clinical strategy to improve engraftment and reduce rejection after allogeneic cell transplantation into the central nervous system.
Statement of Benefit to California: 

We seek to develop a new human neural stem cell therapeutic for chronic cervical spinal cord injury, for which there are no approved treatments. Improvement of a single level of spine function could have a large effect, significantly impacting both quality of life and the economic burden of disease. We also seek to develop new clinical strategies for monitoring potency during cell production and allogeneic cell transplantation, broadly impacting cell based therapies for neurological conditions.

Grant Type: 
Therapeutic Translational Research Projects
Grant Number: 
TRAN1-12891
Investigator: 
ICOC Funds Committed: 
$5 925 602
Disease Focus: 
Neurological Disorders
Stroke
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Translational Candidate

Human induced pluripotent stem cell-derived glial enriched progenitors

Area of Impact

Vascular dementia and white matter stroke, addressing a current bottleneck of poor scale up for existing cell differentiation protocols.

Mechanism of Action

Preliminary in vivo efficacy studies indicate that the MOA is in the promotion of new connections in the brain after white matter stroke, termed axonal sprouting. Axonal sprouting is uniquely present in transplantation of hiPSC-GEPs, and not in transplantation of the precursor stage to hiPSC-GEPs, which is hiPSC-NPCs. Astrocytes promote the formation of new connections in the brain and axonal sprouting, by directly enhancing axonal growth and by promoting the synapses of these growing axons.

Unmet Medical Need

There is no therapy for vascular dementia. The brain responds to this disease, and initiates a reparative response, but is blocked from fully engaging this response. This therapy addresses this condition by delivering a stem cell-derived product that enables recovery in vascular dementia.

Project Objective

Pre-IND meeting with FDA

Major Proposed Activities

  • Pharmacology/Toxicology – Confirmatory in vivo pharmacology studies and pilot in vivo tumorigenicity study
  • CMC – Cell therapy product generation, formulation and qualification of manufacturing process
  • Clin/Reg- Development of clinical trial documents and preparation for pre-IND meeting
Statement of Benefit to California: 

This research will develop a therapy for a disease with no treatment, vascular dementia, that is common and devastating in its consequences. The intellectual property for this therapy is held by a State of California public university (UCLA) and commercialization will directly benefit the State of California.

Grant Type: 
Conference II
Grant Number: 
EDUC1-10860
Investigator: 
ICOC Funds Committed: 
$10 000
Disease Focus: 
Neurological Disorders
Public Abstract: 
Statement of Benefit to California: 

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