Neurological Disorders

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

A Phase 3, Randomized, Placebo-controlled Multicenter Study to Evaluate Efficacy & Safety of Repeated Administrations of NurOwn® in Patients with ALS

Grant Type: 
Clinical Trial Stage Projects
Grant Number: 
CLIN2-09894
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$15 912 390
Disease Focus: 
Amyotrophic Lateral Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Therapeutic Candidate or Device

A cell therapy that delivers high levels of neurotrophic factors to the CNS

Indication

Amyotrophic lateral sclerosis (ALS) or Lou Gehrig Disease

Therapeutic Mechanism

The Cell therapy is aimed at providing high levels of neurotrophic factors directly to the CNS, to support the dying neurons

Unmet Medical Need

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease in which the degeneration and death of motor neurons (MNs) leads to weakness, paralysis and eventually respiratory failure . There remains a great unmet medical need for safe and effective treatments for people with ALS.

Project Objective

Phase 3 completed

Major Proposed Activities

  • Manufacturing of cell therapy product
  • Enrolling 200 patients for the study
  • Run clinical trial
Statement of Benefit to California: 

Manufacturing of the cell therapy product for all US medical centers participating in the study will be exclusively in California
The study will include 2 clinical sites in California that will enroll 80 Californian patients of the the total 200 patients in the study.

RNA-directed therapy for Huntington's disease

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13102
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 408 923
Disease Focus: 
Huntington's Disease
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

We develop a novel adeno-associated viral (AAV) vector-delivered RNA-targeting therapeutic for elimination of toxic RNA causative of Huntington’s disease.

Impact

There are no disease-modifying therapies for Huntington’s disease. Our therapeutic, if successful, will be a first-in-class treatment for this invariably fatal neurodegenerative disorder.

Major Proposed Activities

  • In vitro studies of the RNA-targeting system in human Huntington's disease patient stem cell derived striatal organoids to assess the ability to eliminate toxic RNA foci
  • AAV vector packaging of the CAG-targeting RNA-targeting system to obtain high-titer viral preparations, and in vivo (mouse) safety studies to assess immunogenicity, cytotoxicity and off-target effects
  • In vivo efficacy studies of the RNA-targeting system in a mouse model of Huntington's disease to assess effects on disease-relevant molecular, cellular, behavioral and motor function deficits
Statement of Benefit to California: 

Currently, there is no cure for Huntington’s disease, which currently affects thousands of Californians. The California population will equitably benefit from the development of a therapeutic for Huntington’s disease, which affects the state's residents roughly equally across gender, race/ethnicity and socioeconomic status. Our therapeutic strategy is readily transferrable to a large set of other devastating diseases, multiplying the benefits of development of this new therapeutic modality.

Transplantation of genetically corrected iPSC-microglia for the treatment of Sanfilippo Syndrome (MPSIIIA)

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13077
Investigator: 
ICOC Funds Committed: 
$1 199 922
Disease Focus: 
Metabolic Disorders
Neurological Disorders
Sanfilippo Syndrome/MPS III
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

This research will discover whether transplantation of stem cell-derived microglia can be used to treat Sanfilippo syndrome, a devastating and currently untreatable childhood neurological disease.

Impact

If successful, this research will identify a promising new therapeutic approach for Sanfilippo Syndrome and provide the first evidence that stem cell derived microglia could be used therapeutically.

Major Proposed Activities

  • We will use CRISPR technology to correct disease-associated mutations in the SGSG gene in human stem cell lines that we have generated from patients with Sanfilippo Syndrome (MPSIIIA).
  • Patient-derived and CRISPR corrected stem cells will be differentiated into microglia, an immune cell type that is dysfunctional in MPSIIIA, and then transplanted into a mouse model of this disease.
  • Three months after transplantation we will examine MPSIIIA-associated neuropathologies to determine whether transplantation of genetically-corrected microglia has reduced disease pathology.
  • Microglia that are engineered to produce and secrete higher levels of the missing SGSH enzyme may provide additional long term benefits. We will therefore test the efficacy of this additional approach
  • 6-months after transplantation we will examine neuropathologies to determine whether SGSH secreting microglia improve cognitive function and provide additional long-term benefits in MPSIIIA mice.
  • Analysis of biomarkers, neuropathology, cognitive function, and RNA sequencing of brain cells will be used to determine the optimal approach to reduce MPSIIIA cognitive deficits and neuropathology
Statement of Benefit to California: 

Sanfilippo syndrome (MPSIIIA) is a devastating pediatric neurological disease that effects families of all ethnicities and race including many Californians. Sadly, currently approved therapies provide little benefit. Our research aims to develop a new stem cell-based therapy for MPSIIIA that uses microglia, the immune cell of the brain. If successful, this new approach could also potentially be developed to treat many other neurological diseases that are highly prevalent in California.

Improving the efficacy and tolerability of clinically validated remyelination-inducing molecules using developable combinations of approved drugs

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13063
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 554 126
Disease Focus: 
Multiple Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Research Objective

The candidate is a fixed dose binary small molecule drug combination, consisting of two agents that act synergistically on a multipotent stem cell population in the CNS to stimulate remyelination.

Impact

The proposed studies will address bottleneck issues related to the effect size and tolerability of clinically validated remyelination drug classes.

Major Proposed Activities

  • Establish the maximal and minimal effective concentrations (ECmin and ECmax) and associated levels of efficacy for defined combination-based drug therapies in three populations of rat OPCs.
  • Establish maximal and minimal effective concentrations and associated levels of efficacy for defined drug combinations in a population of human OPCs.
  • Demonstrate reproducible disease modifying activity (i.e., enhancement of remyelination efficiency) in vivo using the cuprizone model of demyelination/remyelination.
  • Complete mouse brain pharmacokinetic (PK), drug-drug interaction and preliminary rodent tolerability studies for 3 OPC differentiation-inducing drug combinations.
  • Complete mechanism of action studies
  • Complete penultimate in vivo efficacy study with kinetic measures and imaging outputs using the cuprizone model of demyelination/remyelination.
Statement of Benefit to California: 

It is estimated that >120,000 California residents suffer from multiple sclerosis (MS). This proposed research aims to provide a disease modifying therapy for MS. It will have a significant beneficial impact, by targeting the regenerative process known as remyelination, which becomes limiting during the progressive phases of MS disease.

Injectable, autologous iPSC-based therapy for spinal cord injury

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13020
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$789 000
Disease Focus: 
Neurological Disorders
Spinal Cord Injury
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

We propose to develop and validate a therapy for spinal cord injuries in which human stem cell-derived neural cells is injected into the injured spinal cord using an injectable gel.

Impact

Our study will address the critical need for an SCI treatment that significantly improves the neurological recovery and hence quality of life of SCI patients and their caretakers.

Major Proposed Activities

  • We will determine if delivering human iPSC-derived neural cells within our injectable gels will improve its ability to graft into and regenerate the injured spinal cord, as compared to saline.
  • We will evaluate if the differences observed in Activity 1 is correlated to differences observed in the functional improvement of the different treatment groups.
  • Using multiple stem cell clones from the same donor as well as from distinct donors, we will evaluate what fraction of clones can pass multiple quality control criteria.
  • We will evaluate if distinct stem cell clones from different individuals can yield similar functional benefits when used to treat spinal cord injuries in rodents.
  • We will evaluate if different stem cell clones from the same individual can yield similar functional benefits when used to treat spinal cord injuries in rodents.
Statement of Benefit to California: 

An estimated 17,900 cases of spinal cord injury are diagnosed in the United States annually, with an estimated lifetime cost of at least $1,217,266 per patient. As the state with the largest population number, California is most significantly affected by SCIs. The success of our proposed research will significantly improve neurological and functional recovery in these patients, enhancing their quality of life, and reducing the economic and public health burden of the disease.

Optimization of a gene therapy for inherited erythromelalgia in iPSC-derived neurons

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-13013
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 157 313
Disease Focus: 
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

The goal of this grant is to develop a gene therapy for a rare painful disorder, Inherited Erythromelalgia (IEM).

Impact

There are currently no FDA approved drugs for IEM, which is caused by a gain-of-function mutation in a sodium channel, Nav1.7. We propose epigenetic repression of Nav1.7 to provide a cure for IEM.

Major Proposed Activities

  • We will characterize the lead gene therapy candidate that will move into IND-enabling studies.
  • We will determine the efficacy of this lead candidate in a clinically relevant human cell population (patients with Inherited Erythromelalgia).
  • We will perform dose range studies to provide preliminary identification of the target organs of toxicity as well as to select doses for future definitive toxicology studies in non-human primates.
  • We will request a FDA meeting,.
Statement of Benefit to California: 

It is estimated that 50 million Americans suffer from chronic pain, with patients relying mostly on opioids. In California, an estimated 45% of drug overdose deaths involved opioids in 2018. We are in dire need of new treatments for chronic pain. Although our first indication will be a rare painful condition, our gene therapy could potentially benefit other individuals with intractable painful conditions, as the gene we are targeting is involved in pain transmission and in many pain conditions.

Development of a new therapeutic for directing target specific stem cell migration and treatment

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-12666
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 129 512
Disease Focus: 
Amyotrophic Lateral Sclerosis
Neurological Disorders
Human Stem Cell Use: 
Adult Stem Cell
Public Abstract: 

Research Objective

A drug-stem cell combination therapy wherein the drug will direct and promote the delivery and distribution of stem cells to the disease site for the optimal therapeutic effect of the stem cells

Impact

Amyotrophic lateral sclerosis (ALS) and the way to deliver and enhance stem cell-based treatment of ALS

Major Proposed Activities

  • Complete the additional in vitro studies and initiate the in vivo studies in SOD1 mouse model
  • Determine whether the combined effect of hNSCs intraparenchymally augmented/guided by SDV1a has a synergistic effect on improving disease onset/progression & symptom-free survival in the SOD1 mouse
  • Establish the preliminary toxicity and pharmacokinetics profiles of SDV1a in mouse model
  • Elucidation of structure and other characteristics; development and validation of analytical procedures
  • Process development and characterization in lab scale, stability study
Statement of Benefit to California: 

This new therapeutic will address a significant unmet medical need in the treatment of amyotrophic lateral sclerosis (ALS) and have important benefits to the patients with ALS and impact on the healthcare and bio industry in California.

AAV9-Cas13 gene therapy for Angelman syndrome

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-12577
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 364 903
Disease Focus: 
Angelman Syndrome
Autism
Neurological Disorders
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

AAV9-Cas13 gene therapy for Angelman syndrome using a first-in-kind mechanism of action that will safely and permanently restore expression of endogenous UBE3A that is deficient in CNS neurons.

Impact

Angelman syndrome is a rare (1 in 15,000 births) neurogenetic disorder caused by loss of UBE3A in the brain, causing severe developmental delay, ataxia and epilepsy. There are no treatments or cures.

Major Proposed Activities

  • Determine the optimal Cas13 guide-RNA for a rodent model.
  • Determine the optimal Cas13 guide-RNA for a humans.
  • Show that the gene therapy improves gene expression in rodent models.
  • Show that the gene therapy improves gene expression in human cells.
  • Show that the gene therapy improves symptoms in rodent models.
  • Show that the gene therapy can be safe and permanent.
Statement of Benefit to California: 

In addition to directly benefiting the ~2,500 children and families living with Angelman syndrome in California, this gene therapy with a first-in-kind mechanism of action could bring new treatments and new opportunities to our state. California has long been a hub of innovation, and creates an environment in which new technologies can be born, fostered, and attract others who want to create a better future for our residents. This activity will help train some of them, and inspire many others.

Stem cell-derived extracellular vesicles to reverse radiation-induced brain injury

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-12400
Investigator: 
Name: 
Institution: 
Type: 
PI
ICOC Funds Committed: 
$1 064 724
Disease Focus: 
Brain Cancer
Cancer
Neurological Disorders
Solid Tumors
Human Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 

Research Objective

These preclinical studies will discover the efficacy of stem cell-derived, nanoscale, extracellular vesicles (candidate) to treat adverse effects of cancer therapy on brain function and cognition.

Impact

Stem cell-derived extracellular vesicles will address the confounders of stem cells (tumors, immunorejection, immunosuppression) & mitigate debilitating side-effects of cancer therapy on the brain.

Major Proposed Activities

  • Demonstrate the effectiveness of IV injections of stem cell-derived, nanoscale, extracellular-vesicles (EVs) to improve cognition in the mouse model of radiation- and chemo-therapy for brain cancers.
  • Determine the ability of EV treatment to protect against adverse effects of cancer therapy including neuro-inflammation, synaptic and micro-vascular damage in the brain.
  • Establish the neurocognitive benefits of injecting stem cell-derived-EV in brain cancer-bearing mice receiving combined radiation- and chemo-therapy (temozolomide, TMZ).
  • Elucidate the impact of stem cell-derived-EV injections on neuropathological hallmarks of radiation- and chemo-therapy (TMZ) in the cancer-bearing mice brains.
  • Determine the safety and rule out the toxicity of stem cell-derived EV treatment in brain and peripheral organs in the mice receiving radiation- and chemo-therapy (TMZ) for brain cancer.
  • Confirm miRNA-124-based mechanism (commonly found within the EV cargo) of stem cell-derived EV-mediated neuroprotection in the mice undergoing radiation- and chemo-therapy for brain cancers.
Statement of Benefit to California: 

In California, nearly 187,000 patients diagnosed with cancer will be alive in 5 years & more than 1.88 million have a history of cancer. Importantly, adult & childhood cancer survivors suffer from severe & persistent cognitive deficits that adversely affect their quality of life (QOL). A stem cell-based therapeutic could reduce inflammation & restore the cognitive function that may significantly improve patient’s QOL, reduce financial hardship on patients, caregivers & the state of California.

Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.

Grant Type: 
Quest - Discovery Stage Research Projects
Grant Number: 
DISC2-12169
Investigator: 
ICOC Funds Committed: 
$250 000
Disease Focus: 
Neurological Disorders
Stroke
Human Stem Cell Use: 
iPS Cell
Public Abstract: 

Research Objective

This grant proposes development of a stem cell based therapy that is derived from human induced pluripotent stem cells. These cells are in the form of a brain support cell, an astrocyte.

Impact

The cell candidate will treat vascular dementia, the second leading cause of dementia, and stroke by overcoming a bottleneck in the ability to make large quantities of the cells for clinical use.

Major Proposed Activities

  • In vivo tumorigenic studies.
  • Development and optimization of potency assays
  • Qualification and stability of cell delivery system.
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.

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