I’m a contrarian with myself, and if I think I can’t do something, then I do it to prove I can.

I never believed I could get along where it’s mostly necessary to know a foreign language.  So I went to Montpellier, a French city with a study-abroad program endorsed by my university.  After a tough breaking-in, I moved in with a wonderful local family.  We spent the evenings and weekends together.  I played soccer with my host brother and on occasion saw my host sisters, each busy doing their own thing elsewhere in l’Hexagone.  I studied the language at Université Paul Valéry, the liberal arts college in Montpellier’s public university system.

Until I studied medicinal chemistry years later, I didn’t know Montpellier as a drug discovery and development hub.  Bausch + Lomb1 and Sanofi-Aventis2 have operations there, as do at least 15 other pharmaceutical companies.  Now Abivax has a potential first-in-class HIV drug that showed good pharmacokinetics and safety in two Phase I clinical trials.  Phase IIa studies, where the drug’s effectiveness will first be examined, are ongoing.3

Abivax’ investigational drug ABX464 (below) may become the first that works by blocking HIV RNA from exiting the infected human cell’s nucleus, so that new viruses cannot be made.  In an infected cell, viral DNA is implanted into the cell’s own, and it’s transcribed by human proteins to make viral RNA.  To complete its life-cycle, the unprocessed RNA must leave the nucleus for the cytoplasm, where it goes into a budding baby virus.  But ABX464 increases the processing, called splicing, so that the RNA gets stuck in the nucleus and destroyed.4,5 The process is shown at a high level in this video.

abx464

There are several reasons to be hopeful about ABX464.  First, because it binds directly to a human protein complex rather than a viral protein, ABX464 might cause less drug resistance than other HIV drugs.  Abivax already reported that no drug resistance was seen in a model, infected human blood cells, after 24 weeks of drug treatment.  Second, although ABX464 binds to a complex that processes both human and viral RNA, only the viral material is affected, which means that normal cell functions may be maintained.  Last, the drug was compared as a single agent versus a modern drug cocktail that includes 3TC, Tenofovir, and Raltegravir in HIV infected mice, and the response to ABX464 was stronger and longer lasting.  The drug’s specific effect on viral RNA and long lasting viral suppression would be useful for a drug that has to be taken for life.5

HIV is an incurable disease for nearly all patients, and the contrarians want to show otherwise.

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Please note that this is not medical advice.

Image of Montpellier’s Place de la Comédie http://www.timeout.com.br/viagem/montpellier/features/1718/montpellier-onde-comer

References:

1. http://www.bausch.com/our-company/worldwide-locations#France

2. http://www.sanofi.fr/l/fr/fr/layout.jsp?cnt=5A972739-6CAA-4BA2-A613-F78B0030B065

3. http://www.abivax.com/en/news-events/press-releases/292-abivax-announces-r-d-day-at-company-s-new-collaborative-laboratory-in-montpellier.html

4. Retrovirology. 2015, 12:30.

5. Retrovirology. 2015, 12:64.

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