Neurological Disorders

Coding Dimension ID: 
303
Coding Dimension path name: 
Neurological Disorders
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: 
Conference II
Grant Number: 
EDUC1-10860
Investigator: 
ICOC Funds Committed: 
$10 000
Disease Focus: 
Neurological Disorders
Public Abstract: 
Statement of Benefit to California: 
Grant Type: 
Late Stage Preclinical Projects
Grant Number: 
CLIN1-11404
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$5 666 077
Disease Focus: 
Neurological Disorders
Spina Bifida
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

Allogeneic Placenta-derived Mesenchymal Stem Cells Seeded on Cook Biodesign® Dural Graft Extracellular Matrix (PMSC-ECM)

Indication

Myelomeningocele (MMC) -or Spina Bifida -diagnosed prenataly

Therapeutic Mechanism

Placenta-derived mesenchymal stem cells (PMSCs) act by a paracrine mechanism, secreting a variety of growth factors, cytokines, and extracellular vesicles. This secretory profile is unique to PMSCs and is responsible for protecting motor neurons from apoptosis, which occurs due to chemical and mechanical trauma when motor neurons are exposed to the intrauterine environment. PMSC treatment increases the density of motor neurons in the spinal cord, leading to improved motor function.

Unmet Medical Need

The current standard of care in utero surgery, while promising, still leaves 58% of patients unable to walk independently. There is an extraordinary need for a therapy that prevents or lessens the severity of the devastating and costly lifelong disabilities associated with the disease.

Project Objective

IND filing, Phase 1/2 trial start-up activities

Major Proposed Activities

  • Manufacture product to supply the proposed studies and clinical trial
  • Assess safety of the therapeutic PMSC product
  • Assess efficacy using clinical-grade product
Statement of Benefit to California: 

There is a high incidence of MMC in CA with 39.1% of the population being of Hispanic or Latino descent, a demographic that is affected by MMC at a disproportionately high rate. The cost to CA is approximately $532,000 per child, but for many, the cost may be several million dollars due to ongoing treatment. Indirect costs include pain and suffering, specialized childcare, and lost time of unpaid caregivers. A therapy for MMC would relieve the tremendous emotional and economic cost burden to CA.

Grant Type: 
Late Stage Preclinical Projects
Grant Number: 
CLIN1-11059
Investigator: 
ICOC Funds Committed: 
$5 811 340
Disease Focus: 
Neurological Disorders
Parkinson's Disease
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

CNS10-NPC-GDNF is a neural progenitor cell line transfected with glial cell line derived neurotrophic factor (GDNF)

Indication

Mid-stage Parkinson's disease (UPDRS stage III or lower)

Therapeutic Mechanism

Degeneration of dopaminergic neurons that project from the substantia nigra to the striatum causes the primary motor symptoms of Parkinson's disease. CNS10-NPC-GDNF cells will be transplanted into the putamen, and are expected undergo limited migration to areas of degeneration, induce sprouting of dopaminergic terminals and protect dopamine cell bodies. The cells can mature into astrocytes that may provide additional protection of degenerating regions through secretion of supportive factors.

Unmet Medical Need

Current treatments provide symptomatic relief of Parkinson's disease (PD), but become less effective over time as they have no effect on the disease process. CNS10-NPC-GDNF is expected to slow the disease progression by inducing sprouting of dopaminergic terminals and protecting dopaminergic cells.

Project Objective

Complete pre-clinical studies, and file an IND.

Major Proposed Activities

  • Manufacture of CNS10-NPC-GDNF to supply the proposed clinical trial
  • Demonstrate longterm lack of tumorigenicity and safety in rats
  • Demonstrate safety and tolerability of CNS10-NPC-GDNF in aged MPTP lesioned non-human primate model of Parkinson's disease
Statement of Benefit to California: 

Parkinson's disease is a debilitating disease, which puts a huge burden on state resources through the need for care givers and medical care. While primarily an effort to reduce patient and family suffering, this project will also ease the cost of caring for PD patients in California if successful. This in turn will attract scientists, clinicians, and biotech companies to the state of California thus increasing state revenue and state prestige in this rapidly growing field.

Grant Type: 
Late Stage Preclinical Projects
Grant Number: 
CLIN1-10953
Investigator: 
Type: 
PI
ICOC Funds Committed: 
$6 000 000
Disease Focus: 
Huntington's Disease
Neurological Disorders
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

The therapeutic candidate is a human Neural Stem Cell product to prevent or delay disease symptoms for treatment of Huntington's disease (HD).

Indication

Huntington’s disease, a progressive, degenerative brain disease, typically strikes in midlife with no disease modifying treatment
treatments exist.

Therapeutic Mechanism

Based on our pre-clinical studies, the human neural stem cells engraft and differentiate into neuronal populations, express the neurotrophic factor BDNF and reduce mutant Huntingtin protein accumulation. Further, host tissue forms synaptic contacts with transplanted cells and may provide new and functional connections to reduce the aberrant cortical excitability in HD. These molecular and histological improvements correlate with improvement in behavior and electrophysiological deficits.

Unmet Medical Need

No treatment currently exists that can slow or prevent the unrelenting progression of Huntington’s disease, a devastating brain disease,
therefore a completely unmet medical need exists.

Project Objective

File an Investigational New Drug request with FDA.

Major Proposed Activities

  • Good Manufacturing Practice (GMP) manufacturing and characterization of the cell product to supply the first in human study.
  • Good laboratory practice (GLP) long term safety, biodistribution and tumorigenicity studies in HD modeled and Wt mice.
  • Investigational New Drug (IND) preparation, publishing and submission .
Statement of Benefit to California: 

The disability, loss of personal freedom and earning potential, and costly institutional care of HD is devastating. Developing a therapeutic product will allow patients to live independently longer after diagnosis, and result in saving considerable costs for healthcare and caregiving, and extending the quality of life for HD patients and their family members. It will also benefit California through new technologies and intellectual property resulting in possible job creation and revenues.

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