Technology Opportunities

Inflammation often named “the secret killer” is a key factor in a large group of diseases affecting and killing millions of people every year. Examples of inflammatory diseases or diseases with key inflammatory components include Arthritis, Alzheimer, Parkinson, ALS, Peritonitis, Colitis, Obesity & Insulin resistance and several types of cancer. Currently, anti-inflammatory drugs, both NSAIDs and steroidal, fail to deliver a solution because they tackle only parts of the inflammatory cascade and induce unacceptable side effects. There is a strong need for specific and efficient anti-inflammatory drugs with minimal side effects. This need is recognized by the pharmaceutical industry which struggles to develop such drugs.

Our Solution
cPLA2 is a major participant in the inflammatory cascade and cPLA2 over production is a major cause of inflammation. We have developed an antisense oligonucleotide based therapy that reduces the overproduction of cPLA2 and successfully combats inflammation as shown in several inflammatory diseases.

Applications
Colon cancer -The administration of the antisense oligonucleotides (AS) but not the corresponding sense oligonucleotides (SE) significantly inhibit cPLA2 protein expression and reduce HT-29 cell proliferation by inducing cell arrest.

Alzheimer’s Disease - Our studies demonstrate that cPLA2 is regulating the production of A and that both neuronal cPLA2 directly, and microglia cPLA2 indirectly, contribute to apoptotic neuronal death. The presence of our antisense oligonucleotides (AS) not only inhibit the excessive production of A but also prevents the indirect and direct neuronal death in culture, indicating towards an efficient treatment for Alzheimer’s disease.

Rheumatoid Arthritis - In-vivo intravenous administration of the antisense oligonucleotides (AS), after development of severe arthritis in a mouse model of CIA, induced remarkable recovery after only a short treatment, as determined by clinical score and by the histological examination of the inflamed joints.

Obesity Induced Insulin Resistance - Initiating obesity and impairment of liver insulin signaling in a mouse model of High Fat Diet was accompanied by neutrophil recruitment to the intra-abdominal fat. Intravenous administration of antisense against cPLA2 prevented the severe liver insulin signaling impairment.

ALS - The elevated expression and activity of cPLA2 in brain and spinal cord of both sporadic and familial ALS patients and in spinal cord of the mouse model of ALS, with SOD1 mutation suggests that cPLA2 may have an important role in the pathogenesis of the disease in all ALS patients. The role of cPLA2 up regulation has been demonstrated also in caspase mediate apoptotic neuronal death induced by oxidative stress. We have shown that inhibition of cPLA2 up regulation that inhibited caspase activation prevented neuronal death, and extended survival of ALS mice.

Patent Status
Patent Pending