Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

Anti-inflammatory approach suppresses cancer metastasis in animal models

An anti-inflammatory drug called ketorolac, given before surgery, can promote long-term survival in animal models of cancer metastasis, a team of scientists has found. The research suggests that flanking chemotherapy with ketorolac or similar drugs -- an approach that is distinct from previous anti-inflammatory cancer prevention efforts -- can unleash anti-tumor immunity. The findings, published in Journal of Clinical Investigation, also provide a mechanistic explanation for the anti-metastatic effects of ketorolac, previously observed in human Read more

I3 Venture awards info

Emory is full of fledgling biomedical proto-companies. Some of them are actual corporations with employees, while others are ideas that need a push to get them to that point. Along with the companies highlighted by the Emory Biotech Consulting Club, Dean Sukhatme’s recent announcement of five I3 Venture research awards gives more examples of early stage research projects with commercial potential. This is the third round of the I3 awards; the first two were Wow! Read more

Elena Martinelli

Clues to how anti-integrin antibody suppresses SIV

In October 2016, Emory and NIAID researchers published results in Science that surprised the HIV/AIDS field.

They showed that treatment with an antibody, on top of antiretroviral drugs, could lead to long-term viral suppression in SIV-infected monkeys. A similar antibody is already approved for Crohn’s disease, and a clinical trial has begun at NIAID testing the effects in people living with HIV.

The HIV/AIDS field is still puzzling over a study led by Emory pathologist Tab Ansari.

All that was achieved even though HIV/AIDS experts are still puzzled by how the antibody works. Last week, Christina Guzzo,with NIAID director Anthony Fauci’s lab, presented new data at the Conference on Retroviruses and Opportunistic Infections in Seattle that provide some clues. But the broader issue of “what is the antibody doing?” is still open.

Let’s back up a bit. The antibody used in the Science paper targets a molecule called integrin alpha 4 beta 7, usually described as a “gut homing receptor” for CD4+ T cells, which are ravaged by HIV and SIV infection.  Study leader Aftab Ansari (right) and Fauci have both said their idea was to stop T cells from circulating into the gut, a major site of damage during acute viral infection.

Integrin alpha 4 beta 7 was also known to interact with the HIV envelope protein. Accordingly, it is possible to imagine some possibilities for what an antibody against integrin alpha 4 beta 7 could be doing: it could be driving T cells to different places in the body or affecting the T cells somehow, or it could be interfering with interactions between SIV and the cells it infects.

The new data from NIAID say that integrin alpha 4 beta 7 is found on the virus itself. This finding makes sense, because SIV and HIV are enveloped viruses — they steal the clothes of the cells they infect and emerge from. [Integrin alpha 4 beta 7 also appears to help the virus be more infectious in the gut, Guzzo’s presentation says.]

So a third possibility appears: the anti-alpha 4 beta 7 antibody is mopping up virus. Perhaps it’s acting like a virus-neutralizing antibody or the anti-CD4 antibody ibalizumab — CD4 is the main viral receptor on T cells. It could explain why the anti-integrin antibody’s effect is so durable; HIV/SIV can mutate to escape neutralizing antibodies directed against the viral envelope protein, but it can’t mutate the clothes it steals! Read more

Posted on by Quinn Eastman in Immunology Leave a comment