STM Platform » GPM Pharmaceutical Development

Signum’s long-term goal is the development of anti-inflammatory pharmaceuticals based on our GPM technology. G-protein mediated inflammation is a major cause or consequence of most disease processes. Arazine^™ (Acetyl-farnesyl-cysteine) competes with isoprenylated G-proteins for sites of interaction with protein targets in the membrane. Arazine^™ and second generation compounds constitute a new class of non-steroidal anti-inflammatories that have the potential to treat an array of inflammatory diseases.

Skin Disease
Arazine^™ and other GPM compounds have several properties that make it a safe therapeutic to treat various skin diseases:

• Arazine^™ is as effective as corticosteroids in reducing acute skin irritation.
• Unlike corticosteroids, Arazine^™ has little effect on epidermal homeostasis, and we have seen no adverse consequences associated with long-term application.
• Unlike corticosteroids, Arazine^™ effects are restricted to the site of application.
• Once it penetrates the skin, Arazine^™ in essence is a naturally occurring amino acid, is bound up by serum protein and is quickly metabolized by the normal course of protein turnover within the body.

Given its safety and effectiveness as an anti-inflammatory, Arazine^™ and other second generation GPM compounds, could provide an effective nonsteroidal alternative for patients suffering from skin diseases such as: rosacea, atopic dermatitis and psoriasis.

Respiratory Disease
Asthma is a chronic condition involving the respiratory system in which the airway constricts and becomes inflamed, often in response to one or more triggers. Chronic obstructive pulmonary disease (COPD) is a group of respiratory pathologies (emphysema, chronic bronchitis, and small airways disease) characterized by airflow that is not fully reversible. Both asthma and COPD are characterized by abnormal inflammatory response to noxious particles as well as airway hyper reactivity. The undesirable side effects of corticosteroids, which are the only effective inhaled anti-inflammatory compounds, suggest a significant possible opportunity for inhaled second-generation Arazine^™ compounds. Currently, we are collaborating with the University of Pennsylvania to assess the effects of GPM compounds on airway inflammation.

Inflammatory Bowel Disease (IBD)
The term IBD covers a group of disorders in which the intestines become severely inflamed, likely as a result of an immune reaction of the body against its own intestinal tissue. The two major types of IBD are:

• Crohn’s disease – can involve any part of the gastrointestinal tract from the mouth to the anus, but most commonly affects the small intestine and/or colon.
• ulcerative colitis (UC) – limited to the colon.

Currently, Crohn’s disease and UC are treated using either anti-inflammatory drugs, corticosteroids and/or immunosuppressants. We believe development of GPM compounds will be an important addition to the current therapeutics on the market for IBD.

Parkinson’s Disease
The nervous system, like the immune system, is highly dependent on cell-to-cell communication and research suggests that neuronal activity can be substantially influenced by the systemic application of Arazine^™ and its derivatives. Results in experiments conducted by a group at Florida A & M University (FAMU) have indicated that these types of agents could be used to block Parkinson-like tremors in rats (link to abstract). Signum has established a collaborative effort with FAMU to develop specific second generation Arazine^™ compounds that are optimized for the treatment of Parkinson’s. Also, we are currently developing PPMs that may also be effective in treating this disease.