Grant Award Details
To validate the L1 RT target in AGS and to explore astrocytes as the source of the inflammatory response in the disease.
Grant Application Details
- Reverse transcriptase inhibitors as a novel therapeutic approach for neurological autoimmune disorders
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.
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.
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.
- Cell Rep (2019) Metabolic and Organelle Morphology Defects in Mice and Human Patients Define Spinocerebellar Ataxia Type 7 as a Mitochondrial Disease. (PubMed: 30699348)
- Elife (2019) Species-specific maturation profiles of human, chimpanzee and bonobo neural cells. (PubMed: 30730291)
- Biol Psychiatry (2018) Modeling the Interplay Between Neurons and Astrocytes in Autism Using Human Induced Pluripotent Stem Cells. (PubMed: 29129319)
- Cell Stem Cell (2017) Modeling of TREX1-Dependent Autoimmune Disease using Human Stem Cells Highlights L1 Accumulation as a Source of Neuroinflammation. (PubMed: 28803918)
- J Cell Sci (2016) Bradykinin promotes neuron-generating division of neural progenitor cells through ERK activation. (PubMed: 27528403)