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darunavir + ritonavir + dolutegravir + tenofovir alafenamide
- Development stage
- Phase 1
- Lead developer
- National Institute of Neurological Disorders and Stroke
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This four-drug antiretroviral regimen, consisting of darunavir, ritonavir, dolutegravir, and tenofovir alafenamide, is being investigated by the National Institute of Neurological Disorders and Stroke (NINDS) for the treatment of amyotrophic lateral sclerosis (ALS). The therapy aims to suppress the expression of Human Endogenous Retrovirus-K (HERV-K), a retroelement that has been found to be activated in the brains and spinal cords of a subset of ALS patients and is hypothesized to contribute to neurodegeneration. In this combination, darunavir serves as a protease inhibitor, dolutegravir as an integrase inhibitor, and tenofovir alafenamide as a nucleoside reverse transcriptase inhibitor, while ritonavir is utilized as a pharmacokinetic booster to increase the systemic exposure of darunavir by inhibiting the CYP3A4 enzyme.
- Other names
- Antiretroviral therapy for HERV-K suppression in ALSHERV-K suppression regimen
02
Targets
CYP3A4 (Cytochrome P450 3A4)Integrase allosteric pocket (HIV)PR (Progesterone receptor)Human immunodeficiency virus type 1 reverse transcriptaseHERV-K (Human endogenous retrovirus K)NS5B (Hepatitis C virus non-structural protein 5B (NS5B) RNA-dependent RNA polymerase)
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