eNSAID Technology - "Super Aspirin"
Non-Steroidal anti-Inflammatory Drugs
NSAIDs and Their Limitations
Non-steroidal anti-inflammatory drugs (NSAIDs) are a ubiquitous class of molecule. Derived from plant materials, these medicines have been used for centuries to treat high fever, pain and to reduce inflammation. The prototypical NSAID, Aspirin, became available as a synthetic product in 1897 when Felix Hoffman and Bayer commercialized their synthetic process. Other synthetic NSAIDs such as Naproxen and ibuprofen were developed in the 1950s and this class of drug now accounts for over 70 million annual prescriptions and 30 billion over the counter US sales.
Although NSAIDs are broadly applicable, there are serious concerns about their use in settings that require chronic dosing or where high doses are required. The incidence of serious side effects such as gastrointestinal ulcers and bleeding, kidney disease and cardiovascular events such as myocardial infarction and stroke. For example, the 2008 deaths from NSAID-related GI complications (16,550) is comparable to deaths associated with AIDs (16,685) and greater than the number of deaths from multiple myeloma, asthma, cervical cancer or Hodgkin’s disease. Consequently, their long-term use is not feasible and the search for improved NSAIDs justified.
The Search for a Better NSAID: Coxibs
NSAIDs inhibit cyclooxygenase (COX), a key catalyst in the formation of prostaglandins and thromboxane, that are central to inflammatory signaling. Two key subtypes, COX-1 and COX-2 have been identified with most NSAIDs nonselectively inhibit both isoforms. Simplistically, COX-1, a constitutively expressed house-keeping enzyme, was implicated in the side effects of NSAIDs, while inhibition of COX-2 produced the positive, anti-inflammatory effects. Selective COX-2 inhibitors, known as coxibs, have been shown to be as effective as traditional NSAIDs for the indications for which they have been approved and appear to have superior safety when used in the short-term. However, long-term use has been associated with increased risk of myocardial infarctions or strokes resulting in the withdrawal of Rofecoxib (Vioxx) and Valecoxib (Bextra). These increased risks are seen as a coxib class effect and this has essentially stalled any further research in this area.
eNSAIDs: Building Better and Safer NSAIDs:
NBS-1120 and the other NOSH-NSAIDs represent a new class of Enhanced Nonsteroidal Anti-Inflammatory Drugs that have shown in animal models to have superior activity and safety compared to the patent NSAIDs. In particular, the improved safety profile, that may translate to teh clinic, would result in the ability to dose the eNSAIDs chronically, potentially addressing indications where chronic dosing with NSAIDs is desirable, but currently not feasible.
Importantly, the ability to administer anti-inflammatory drugs chronically at relatively high doses could enable their use as alternatives to opioids and help combat the opioid epidemic.
