Publications by authors named "R L Mosley"
Article Synopsis
- Regulatory T cells (Tregs) can help manage immune responses but lack specific targeting in treating neurodegenerative diseases like Alzheimer's, which this study addresses by engineering Tregs to target amyloid-beta (Aβ) antigens.
- The researchers created Tregs with a transgenic T cell receptor (TCR) specific for Aβ using CRISPR-Cas9 technology and tested their effectiveness in a mouse model of Alzheimer's disease.
- Results showed that these engineered Tregs successfully reduced Aβ levels, improved cognitive functions, and had a positive impact on brain health, highlighting their potential as a targeted therapy for Alzheimer's disease.
Objectives: To evaluate the linkage between age and deficits in innate and adaptive immunity which heralds both Alzheimer's disease (AD) onset and progression. The pathobiological events which underlie and tie these outcomes remain not fully understood.
Methods: To investigate age-dependent immunity in AD, we evaluated innate and adaptive immunity in coordinate studies of regulatory T cell (Treg) function, T cell frequencies, and microglial integrity.
Synucleinopathies are a group of neurodegenerative disorders characterized by pathologic aggregates of neural and glial α-synuclein (α-syn) in the form of Lewy bodies (LBs), Lewy neurites, and cytoplasmic inclusions in both neurons and glia. Two major classes of synucleinopathies are LB disease and multiple system atrophy. LB diseases include Parkinson's disease (PD), PD with dementia, and dementia with LBs.
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- The study assessed the long-term safety and tolerability of sargramostim (Leukine) in five patients with Parkinson's disease (PD) over a 33-month period, examining its effects on immune response and motor functions.
- Adverse effects noted included injection-site reactions, elevated white blood cell counts, and bone pain, but no significant side effects were found during blood analyses related to long-term use.
- Results indicated stable motor function scores and increased regulatory T cell activity, suggesting that sargramostim may provide immune benefits and maintain clinical stability in PD, warranting further investigation in larger trials.
Treatment of HIV-1-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine was followed by dual CRISPR-Cas9 C-C chemokine receptor type five (CCR5) and HIV-1 proviral DNA gene editing. This led to sequential viral suppression, restoration of absolute human CD4 T cell numbers, then elimination of replication-competent virus in 58% of infected mice. Dual CRISPR therapies enabled the excision of integrated proviral DNA in infected human cells contained within live infected animals.
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