Therapeutic Focus - Influenza
Influenza
Intrucept Biomedicine has selected influenza as one of its therapeutic targets because of the worldwide need for safe and effective antivirals that could address both seasonal flu requirements as well as the threat of pandemic flu.
Seasonal flu. Influenza is a contagious respiratory illness caused by influenza viruses. It can cause mild to severe illness, and at times can lead to death. The best way to prevent this illness is by getting a flu vaccination each fall. According to the Centers for Disease Control and Prevention (CDC), every year in the United States, on average:
- Between 5% and 20% of the population gets the flu;
- More than 200,000 people are hospitalized from flu complications, and;
- About 36,000 people die from flu.
Older people, young children, and people with certain health conditions, are at high risk for serious flu complications, which can include bacterial pneumonia, dehydration, and worsening of chronic medical conditions, such as congestive heart failure, asthma, or diabetes. Children may get sinus problems and ear infections.
While the most effective way of protecting against influenza is through prophylaxis, and "flu" vaccines are generally effective in preventing wide outspreads of the disease, vaccines with the right antigenic determinants may not always be widely available and do not help those already exposed. Antiviral drugs can be used for both the prevention of flu and the treatment of those already exposed.
In the United States, 4 antiviral medications (amantadine, rimantadine, oseltamivir, and zanamivir) are approved for treatment of influenza A viruses, although supplies of zanamivir are currently limited. During the 2005-2006 influenza season, CDC recommends against the use of amantadine or rimandatine for the treatment or prophylaxis of influenza in the United States because of rapidly growing resistance (>80% of strains) to this class of drugs. So far, the neuraminidase inhibitors zanamivir and oseltamivir continue to be effective against influenza strains but resistance could also become problematic for these drugs.
Pandemic flu. Of serious concern to health agencies worldwide is the potential for emergence of highly virulent and difficult to control strains of influenza. With rapid transmission among populations, such strains could trigger a pandemic – a worldwide spread of the virus leading to high morbidity and mortality. Pandemics arise when there is a sudden change in the antigenic determinants in either of the two major proteins on the surface of the influenza A virus (the hemagglutinin or "HA" protein or the neuraminidase or "NA" protein), so that the virus escapes control by antiviral drugs or vaccination.
During the 20th century, the emergence of several new influenza A virus subtypes caused three pandemics, all of which spread around the world within a year of being detected. These included the 1918-19 "Spanish flu," [A (H1N1)], caused the highest number of known influenza deaths, with more than 500,000 casualties in the United States and up to 50 million deaths world wide. Many people died within the first few days after infection, and others died of secondary complications. Nearly half of those who died were young, healthy adults. Influenza A (H1N1) viruses still circulate today after being introduced again into the human population in 1977
The 1957-58 "Asian flu," [A (H2N2)], caused about 70,000 deaths in the United States. First identified in China in late February 1957, the Asian flu spread to the United States by June 1957. And the 1968-69 "Hong Kong flu," [A (H3N2)], caused about 34,000 deaths in the United States. This virus was first detected in Hong Kong in early 1968 and spread to the United States later that year. Influenza A (H3N2) viruses still circulate today. Both the 1957-58 and 1968-69 pandemics were caused by viruses containing a combination of genes from a human influenza virus and an avian influenza virus. The 1918-19 pandemic virus appears to have an avian origin.
A new threat. Recently (2004-06), a great deal of concern has been expressed over the increasing number of deaths from a new type of avian flu, [A H5N1], which can be transmitted from infected birds to man. Should the virus mutate and become easily transmissible among humans, and should its control through vaccination or antiviral therapy prove difficult, H5N1 strains could be the genesis of a new and dangerous pandemic. No vaccine yet exists for H5N1 and the virus has already shown resistant to two of the four approved antiviral drugs (amantadine and rimantadine). Resistance to neuraminidase inhibitors zanamivir and oseltamivir has been noted in many isolates. This raises particular concerns about the effectiveness of available drugs to treat an avian flu outbreak.
Intrucept Biomedicine’s research focuses on a new class of proteins that could halt the spread of all strains or types of influenza viruses tested. The availability of a safe, potent, easily obtained and cost-effective new drug class could contribute significantly to the management of influenza and help minimize serious complications that can follow primary viral infection.
