Peptide T

Peptide T is an HIV entry inhibitor discovered in 1986 by Candace Pert, a US neuroimmunologist.[1] Peptide T, and its modified analog Dala1-peptide T-amide (DAPTA), a drug in clinical trials, is a short peptide derived from the HIV envelope protein gp120 which blocks binding[2] and infection[3] of viral strains which use the CCR5 receptor to infect cells.

Peptide T
Names
IUPAC name
L-Alanyl-L-seryl-L-threonyl-L-threonyl-L-threonyl-L-asparaginyl-L-tyrosyl-L-threonine
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C35H55N9O16
Molar mass 857.872 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Peptide T has several positive effects related to HIV disease and Neuro-AIDS.[4] A FDG-PET neuro-imaging study in an individual with AIDS dementia who completed a 12-wk treatment with intranasal DAPTA, showed remission in 34 out of 35 brain regions after treatment.[5] A placebo-controlled, three site, 200+ patient NIH-funded clinical trial, which focused on neurocognitive improvements, was conducted between 1990 and 1995. The results showed that DAPTA was not significantly different from placebo on the study primary end points. However, 2 of 7 domains, abstract thinking and speed of information processing, did show improvement in the DAPTA group (p<.05). Furthermore, twice as many DAPTA-treated patients improved, whereas twice as many placebo patients deteriorated (P=.02). A sub-group analysis showed that DAPTA had a treatment effect and improved global cognitive performance (P=.02) in the patients who had more severe cognitive impairment.[6]

An analysis of antiviral effects from the 1996 NIH study showed peripheral viral load (combined plasma and serum) was significantly reduced in the DAPTA-treated group.[7] An eleven-person study for peptide T effects on cellular viral load showed reductions in the persistently infected monocyte reservoir to undetectable levels in most of the patients.[8] Elimination of viral reservoirs, such as the monocytes, is an important treatment goal.[9]

As of 2015, peptide T is not currently available as a treatment in any country.

In the 2013 biographical film Dallas Buyers Club,[10] protagonist Ron Woodroof (Matthew McConaughey) promotes the use of injected peptide T as a treatment for HIV/AIDS and Alzheimer's Disease and sues the FDA over their efforts to limit his ability to use peptide T, as it was an unapproved medicine. Additional information on Woodroof's court challenge to the FDA related to his obtaining access to peptide T can be found in the article by Marsha Cohen in Hastings Constitutional Law Quarterly (vol.18:471) Cohen, 1991. Woodroof's challenge was in part responsible for the 1987 revisions to the FDA investigational drug regulations that expanded access to experimental drugs for patients with serious diseases with no alternative therapies.

References
  1. Pert CB, Hill JM, Ruff MR, et al. (Dec 1986). "Octapeptides deduced from the neuropeptide receptor-like pattern of antigen T4 in brain potently inhibit human immunodeficiency virus receptor binding and T-cell infectivity". Proc Natl Acad Sci USA. 83 (23): 9254–8. Bibcode:1986PNAS...83.9254P. doi:10.1073/pnas.83.23.9254. PMC 387114. PMID 3097649.
  2. Polianova MT, Ruscetti FW, Pert CB, Ruff MR (Aug 2005). "Chemokine receptor-5 (CCR5) is a receptor for the HIV entry inhibitor peptide T (DAPTA)". Antiviral Res. 67 (2): 83–92. doi:10.1016/j.antiviral.2005.03.007. PMID 16002156.
  3. Ruff MR, Melendez-Guerrero LM, Yang QE, et al. (Oct 2001). "Peptide T inhibits HIV-1 infection mediated by the chemokine receptor-5 (CCR5)". Antiviral Res. 52 (1): 63–75. doi:10.1016/S0166-3542(01)00163-2. PMID 11530189.
  4. Ruff MR, Polianova M, Yang QE, Leoung GS, Ruscetti FW, Pert CB (Jan 2003). "Update on D-ala-peptide T-amide (DAPTA): a viral entry inhibitor that blocks CCR5 chemokine receptors". Curr. HIV Res. 1 (1): 51–67. doi:10.2174/1570162033352066. PMID 15043212.
  5. Villemagne VL, Phillips RL, Liu X, Gilson SF, Dannals RF, Wong DF, Harris PJ, Ruff M, Pert C, Bridge P, London ED (July 1996). "Peptide T and glucose metabolism in AIDS dementia complex". J. Nucl. Med. 37 (7): 1177–80. PMID 8965193.
  6. Heseltine PN, Goodkin K, Atkinson JH, Vitiello B, Rochon J, Heaton RK, Eaton EM, Wilkie FL, Sobel E, Brown SJ, Feaster D, Schneider L, Goldschmidts WL, Stover ES (January 1998). "Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment". Arch. Neurol. 55 (1): 41–51. doi:10.1001/archneur.55.1.41. PMID 9443710.
  7. Goodkin K, Vitiello B, Lyman WD, et al. (Jun 2006). "Cerebrospinal and peripheral human immunodeficiency virus type 1 load in a multisite, randomized, double-blind, placebo-controlled trial of D-Ala1-peptide T-amide for HIV-1-associated cognitive-motor impairment". J. Neurovirol. 12 (3): 178–89. doi:10.1080/13550280600827344. PMID 16877299. S2CID 12925475.
  8. Polianova MT, Ruscetti FW, Pert CB, et al. (Jul 2003). "Antiviral and immunological benefits in HIV patients receiving intranasal peptide T (DAPTA)". Peptides. 24 (7): 1093–8. doi:10.1016/S0196-9781(03)00176-1. PMID 14499289. S2CID 40797488.
  9. Crowe SM, Sonza S (Sep 2000). "HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: a further obstacle to eradication". J. Leukoc. Biol. 68 (3): 345–50. PMID 10985250.
  10. Dallas Buyers Club. Dir. Jean-Marc Vallée. Perf. Matthew McConaughey. Truth Entertainment, Voltage Pictures; Focus Features (US), 2013.
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