Disease Focus: Neurological Disorders
Global gene expression profiling of single inhibitory neurons derived from human stem cells
Autologous therapy for Parkinson’s disease: single cell RNAseq for in depth characterization of transplanted cells
Inhibitory interneurons derived from human induced pluripotent stem cells to treat stroke
Research Objective Allogeneic Human induced pluripotent stem cells-derived inhibitory interneuron therapy product encapsulated in a hyaluronan/VEGF nanoparticle hydrogel for the treatment of stroke Impact Previous stem cell-based technologies had poor survival, differentiation, and minimal migration within the peri-infarct brain region and were unable to restore neurological functions after stroke. Major Proposed Activities MILESTONE 1: Determine […]
Gene-corrected human microglia for the treatment of adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
Research Objective The research proposed here will support the development of NGL-101, a cell therapy for treating adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Impact Successful development of NGL-101 will result in a life-altering therapy for patients suffering from ALSP and provide proof of concept for treating other microglia diseases. Major Proposed Activities […]
Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS
Research Objective Patient specific stem cells (iPSCs) to model ALS and identify a broadly acting therapeutic intervention Impact Heterogenous patient population, dire need for broadly acting therapeutic interventions Major Proposed Activities Compare the in vitro efficacy of up to 10 lead candidate VAV2 ASOs to rescue the survival of iNs from 30 locally and nationally […]
C9orf72 repeat expansion-tuned allelic suppression by CRISPRi as an ALS therapy
Research Objective We aim to discover an adeno-associated viral (AAV) CRISPRi gene therapy for amyotrophic lateral sclerosis (ALS) patients with hexanucleotide repeat expansions in the C9orf72 gene. Impact This therapy can be administered intravenously once, have long lasting effects, and is indicated for all ALS patients who carry repeat expansions of varying lengths and toxicity […]
Treatment of Myasthenic Syndrome due to Choline Acetyltransferase Deficiency Using AAV9-mediated Gene Therapy
Research Objective Use of a viral vector to transport a normal gene to children with severe motor and respiratory disabilities caused by an inborn defect of the choline acetyltransferase (ChAT) gene. Impact Treatment of an incurable disease in infants and potential amelioration of symptoms of neuro degenerative diseases with deficient cholinergic system such as Alzheimer […]
A First-in-Class Treatment for Progressive Multifocal Leukoencephalopathy Via Multimodal Immune System Engineering
Research Objective We propose to discover genome- and epigenome-edited allogeneic T cells engineered to selectively target JCV as a potentially lifesaving treatment for progressive multifocal leukoencephalopathy (PML). Impact If successful, we would revolutionize treatment for PML patients in whom T cell immunity cannot be restored or boosted and unable to wait for adoptive transfer of […]
Excitatory spinal interneurons from human pluripotent stem cells to treat spinal cord injury
Research Objective The primary objective of this research is to test whether excitatory human V2a spinal interneurons engineered from PSCs can repair the damaged spinal cord and restore motor function. Impact Currently no existing therapies are capable of repairing the injured spinal cord. Our therapeutic cell candidate – human ‘V2a’ spinal interneurons – could address […]
Gene Therapy for SLC6A8 Creatine Transporter Disorder
Research Objective The objective is to define a final therapeutic candidate for an effective gene therapy for mutations of the creatine transporter SLC6A8, a major cause of X-linked intellectual disability (ID). Impact This disorder results in severe ID, autistic-like behavior, seizures, & lack or delay of speech with no treatment. Improving brain transduction is essential […]