Developing Directly Reprogrammed Human Neurons to Investigate the Molecular Basis of Neurodegeneration in HIV and Aging
Purpose
The prevalence of HIV-1 associated neurocognitive disorders (HANDs) is 30% . Advancing age is strongly associated with increased HAND prevalence and investigating the molecular basis of synaptodendritic injury and neurocognitive decline in this context is paramount. Recently the ability to generate directly induced neurons (iNs) from patient-derived fibroblasts has been demonstrated. Unlike the immature neuronal populations generated from induced pluripotent stem cells (iPSCs) iNs reportedly retain aging-associated characteristics of the donor. In this proposal we aim to develop directly induced neurons (iNs) from HIVnegative individuals that retain age-associated transcriptional signatures. We will then determine if directly induced neurons (iNs) derived from HIV-positive individuals reveal age- and additional HIV disease-associated transcriptional signatures.
Condition
- Human Immunodeficiency Virus
Eligibility
- Eligible Ages
- Between 18 and 74
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- HIV negative or HIV positive 18 - 40 years of age male or female OR HIV negative or HIV positive 50 - 74 years of age; male or female
- For both HIV negative and HIV positive participants: English language fluency
- For HIV negative and HIV positive participants: Ability and willingness of participant to give written informed consent
- For both HIV negative and HIV positive participants: If female negative Beta-HCG (human chorionic gonadotropin) pregnancy test
- For both HIV negative and HIV positive participants: Agrees to the collection storage and use of skin and blood samples for research purposes
- For HIV negative participants: Non-reactive HIV test at screening/enrollment
- For HIV positive participants: Positive HIV-1 serology treatment for at least one year with combination antiretroviral therapy plasma HIV-1 RNA levels below 50 copies/ml for at least 6 months prior to screen visit as evidenced by lab results from their primary care provider
Exclusion Criteria
- For all participants: Allergy to lidocaine
- For all participants: Current skin disorder (e.g. psoriasis atopic dematitis eczema)
- For all participants: Bleeding diathesis or current use of anticoagulants
- For all participants: History of head injury with loss of consciousness greater than thirty minutes
- For all participants: History of severe neurological (e.g. multiple sclerosis seizure disorder) or Diagnostic and Statistical Manual Five Edition (DSM-V) pschyiatric illness that affects cognitive functioning (e.g. schizophrenia biopolar affective disorder)
- For all participants: Current diagnosis of major depression disorder as assessed by the patient health questionnaire nine item depression scale (PHQ-9) and not on stable antidepressant medication > 30 days
- For all participants: DSM-V criteria for severe alcohol/substance use disorder within 1 year prior to screen (excluding marijuana)
- For all participants: History of clinically significant cardiac disease such as myocardial infarction congestive heart failure or cardiac arrhythmia requiring treatment
- For all participants: Significant renal disease poorly controlled diabetes chronic inflammatory disease
- For all participants: Use of immunomodulators (e.g. interleukins interferons cyclosporine) HIV vaccine systemic cytotoxic chemotherapy or investigational therapy within 1 year of study entry
- For all participants: Systemic steriod therapy within 30 days of screening visit
- For all participants: Any other clinical conditions or prior to enrollment treatment in the opinion of the investigator would make the subject unsuitable for the study or unable to comply with the requirements of the protocol
- For all participants: Laboratory values obtained within 30 days prior to study entry: PT/PTT > 1.5 x control Positive Hepatitis C antibody (HepC Ab+) Positive Hepatitis B surface antigen (Hbs Ag+) Absolute neutrophill count (ANC) < 500 cells/mm3 Platelet count < 80000/mm3 Hemoglobin < 9.0 g/dl Calculated creatinine clearance < 60 mL/minute AST (SGOT) ALT (SGPT) or alkaline phosphatase > 5.0 times the upper limit of normal (ULN) Total bilirubin > 2.5 x ULN (isolated Bilirubin > 2 x ULN is acceptable if direct Bilirubin is < 35%
- Serologic evidence of untreated syphilis
- For all participants: History of keloids formation
Study Design
- Phase
- Study Type
- Observational
More Details
- Status
- Recruiting
- Sponsor
- Rockefeller University