Chronic degenerative and inflammatory diseases are associated with the malfunction of a number of key signaling proteins within each cell - proteins such as MAPK, JNK, ERK, ΔFosB, PI3K, mTOR etc. In most cases the disease is the result of excessive activity of one or more of these signaling proteins, other times it is under-activity, and other times simply wrong activity.
However, despite suspecting which signaling proteins are the main culprits in different diseases, our critical reliance on these proteins for whole-of-body function has put them off-limits as drug targets.
The Filamon 'breakthrough' is the discovery of a way to overcome the problem through an indirect approach - instead of a frontal attack on individual signaling proteins with no consideration of how or even whether they are misbehaving, Filamon drugs are designed to target a small number of upstream master controls that oversee the way that the various signaling proteins talk to each other. The result is being able to rebalance these proteins when behaving abnormally, whatever the nature of that abnormal behaviour, without affecting their normal behaviour in the rest of the body.
The Filamon pipeline is built around three such master controls known to be major players in the areas of cancer, cardiovascular disease, vision loss, neurodegenerative diseases and psychiatric illnesses.
The complex of the enzyme, Group IIA secretory phospholipase A2 (hGIIA-sPLA2 or simply, hGIIA) in combination with the cytoskeleton protein, vimentin, has broad effects on a wide range of signal transduction pathways.
Malfunction of the hGIIA-vimentin interaction process has been implicated in autoimmune diseases, cardiovascular disease (atherosclerosis), neurodegenerative diseases and cancer (chronic inflammation).
In cancer, the inflammation stemming from abnormal hGIIA-vimentin function results in the promotion of tumour growth, angiogenesis (new blood vessel growth), invasiveness and immune evasion.
Tribbles 2 (Trib2) is a protein (pseudokinase) that acts as a scaffold for a wide range of enzyme functions essential to a cell's function and survival, including proteins involved in signaling pathways.
Trib2 doesn't lead to a single function itself like other proteins, but rather, like the hGIIA-vimentin complex, acts as an enabler for hundreds of other protein-protein interactions to occur, such as in the signal transduction relay phenomenon.
The problem arises when Trib2 levels become excessive, a situation known to:
- Promote tumour aggression (Trib2 is linked to aggressive forms of melanoma, lung, liver, brain and colorectal cancers, neuroendocrine tumours (NETS) and acute myelogenous leukemia)
- Block protective immune responses, allowing cancer cells to flourish
- Promote resistance to chemotherapy, resulting in treatment failure
- Promote inflammation, helping to create a tumour environment that encourages cancer growth
- Promote inflammation in artery walls helping to contribute to the formation of atherosclerosis.
(Undisclosed) regulator of gene transcription
Known as the LK-BT2 platform, the target of this platform is an undisclosed (for commercial-in-confidence reasons) target that regulates the genetic control over a range of signal transduction pathways involving MAPK, ERK, JNK, AP-1, ΔFosB and VEGF signaling.
Pre-clinical studies carried out on this target show its malfunction to be involved in cancer growth (including angiogenesis and T-cell exhaustion), cardiovascular disease and chronic inflammation.