RESEARCH AND DEVELOPMENT
Adiga Life Sciences Inc. is currently conducting research and development in a number of therapeutic areas, with the common theme of investigating the potential to deliver improved health outcomes to patients by modulating the activity of the immune system. Allergy can be simply described as an unreasonably inflammatory response by the immune system to a specific allergen. Allergens are usually proteins contained in an organic material to which an individual is allergic. It is being increasingly recognized that the pathology of many other diseases is also driven by abnormal and undesirable immune responses, often to protein components of oneself.
The immune system is a complex process involving numerous different cell types and chemical signals. There are certain types of immune cells that are specifically designed to roam the defensive perimeter of the body and scrutinize foreign materials for their potential to cause harm. If a material is regarded as harmful those immune cells will initiate a cascade of events designed to eradicate it from the system. Broadly speaking, this results in an inflammatory response.
Uncontrolled inflammation would be harmful to the body, and are regulated by anti-inflammatory processes. In health we are unaware of the ongoing equilibrium between pro- and anti-inflammatory processes ongoing inside us. In people with allergy, or auto-immune disease, however, the balance of these processes is for some reason lost, and inflammation leading to disease symptoms often predominates.
Traditional immunotherapy using allergen extracts against allergy is based on the observation that some sufferers of allergy gradually desensitize over long periods (often years) of exposure to low amounts of allergen administered by injection. The exact mechanisms of this action are not well understood, and compared to conventional medicines, allergen extracts are poorly characterized. Clinical effectiveness is therefore modest and often leads to side effects such as anaphylaxis which can be severe.
Adiga Life Sciences is therefore investigating ways of promoting the anti-inflammatory, or “tolerogenic” response to the specific allergens or proteins that cause allergy and other diseases. From an understanding of the molecular targets of unwanted immune responses, we search for small protein fragments (peptides) that may act as handles for recognition (“T cell epitopes”) by human immune cells. Large numbers of peptides are then tested in blood samples obtained from sufferers of the disease under study to evaluate which are most relevant. A prototype peptide vaccine is then designed on the basis of these results, and submitted for preclinical safety studies to enable progression into clinical studies of safety and efficacy.
It is estimated that nearly 40 million North Americans suffer from seasonal allergies and that ragweed is the primary cause of allergies in the late summer and fall. In fact, the third National Health and Nutrition Examination Surveys (NHANES III) showed that over a quarter of the population had positive test responses to ragweed allergens. Symptoms of ragweed allergy include rhinoconjunctivitis, asthma, and more rarely contact dermatitis/urticaria. In many people these symptoms cause sleep problems leading to fatigue, loss of concentration and poor performance at work and school. Current management of ragweed allergy symptoms includes allergen avoidance and medication. However, it can be difficult to avoid outdoor allergens and most of the medication available is palliative.
Adiga Life Sciences is currently evaluating the safety and clinical effects of a novel peptide immunotherapy against ragweed allergy in clinical studies being conducted in Ontario.
Allergy to cat dander is one of the most common forms of allergic disease in the continental US and Europe. The symptoms of allergic rhinitis and/or asthma significantly reduce quality of life and for many people total avoidance of exposure to cats is very difficult. Furthermore, it is now suspected that allergy to cats is strongly linked with the prevalence of asthma. Existing medications for allergic rhinoconjuctivitis arising from cat allergy are essentially palliative and are required to be taken continuously unless exposure to cats can be avoided completely.
Adiga Life Sciences is currently evaluating the safety and clinical effects of a novel peptide immunotherapy against cat allergy in studies being conducted in Ontario. Adiga will also be involved in the upcoming Phase III program that will evaluate the safety and efficacy of the immunotherapy in sites across Canada and the US.
Allergy to grasses is a well recognized disease worldwide. At least 40% of allergic patients worldwide are sensitized to grass pollen allergens, and the majority of sufferers of hay fever or seasonal allergies are allergic to grass pollens. In the third National Health and Nutrition Examination Surveys (NHANES III), approximately one quarter of the population tested positive to perennial Rye grass, and nearly one fifth of the population tested positive to Bermuda grass. The prevalence of allergy to many other grass species is also high. Allergens derived from various grass pollens are a major cause of asthma, rhinitis and eczema in allergic individuals throughout the world.
Adiga Life Sciences is currently evaluating the safety and clinical effects of a novel peptide immunotherapy against grass allergy in a clinical study being conducted in Ontario.
House Dust Mite Allergy
House Dust Mites (HDM) are arachnids that infest bedding, carpet, upholstered furniture and fabric. Their main food source is human skin scales, and they grow best in warm, humid environments. In the third National Health and Nutrition Examination Surveys (NHANES III), over a quarter of the population tested positive to HDM allergen. Exposure to house dust mite (HDM) allergen in sensitized patients is associated with poorer lung function, greater medication requirements, exacerbation of asthma symptoms and chronic rhinosinusitis. In contrast to most other allergens, sufferers of HDM allergy cannot see the source of their allergies and may suffer symptoms for many years until diagnosis is finally achieved via skin prick test. Avoidance of allergen is very difficult, particularly in humid environments and existing treatments are mostly palliative.
Adiga Life Sciences is currently evaluating the safety and clinical effects of a novel peptide immunotherapy against HDM allergy in a clinical study being conducted in Ontario.
Birch Tree Allergy
Allergy to tree pollen is common in early spring and is most easily identified clinically by onset of symptoms that precedes pollination of the grasses. Extensive cross-reactivity between trees means that individuals allergic to one member of a tree family (for example the Betulaceae family which contains birch, hazelnut and alder among others) will develop allergic reactions upon exposure to others. In the third National Health and Nutrition Examination Surveys (NHANES III), approximately 12% of the population tested positive to birch. Birch pollen allergy is also extremely prevalent in northern Europe and represents the primary family of trees eliciting symptoms of allergy. Furthermore allergic cross-reactivity is well documented between certain foods and members of the birch family. For example the oral allergy syndrome (OAS) is characterised by allergic symptoms upon ingestion of food is such as Apple, carrots and hazelnut. That is a vaccine capable of ameliorating respiratory allergies caused by the birch family will also have a beneficial effect on associated food allergy.
Adiga Life Sciences is currently screening candidate peptides for immunotherapy development using blood samples from birch allergic individuals. This work is being performed at McMaster University.
Alternaria is a mould which releases spores containing allergens in both internal and external environments. Damp internal environments are frequently associated with the growth of a variety of mould which can give rise to chronic symptoms of allergy and asthma. Moreover, seasonal release of spores by mould in the external environment can give rise to acute increases in hospital admissions for asthma exacerbations. Intensive release of spores within a very short period (for example in early July for Alternaria) give rise to airborne levels of allergen that far exceed those achieved by pollen allergens such as those in grass and ragweed.
Adiga Life Sciences is currently screening candidate peptides for immunotherapy development using blood samples from Alternaria allergic individuals. This work is being performed at McMaster University.
Other Areas of Research
Adiga is currently engaged in research on a number of other allergens including birch tree, alternaria (mould) and Japanese Cedar.
Allergy to Birch tree pollen is common in early spring and is most easily identified clinically by onset of symptoms that precedes pollination of the grasses. In the third National Health and Nutrition Examination Surveys (NHANES III), approximately 12% of the population tested positive to birch. Birch pollen allergy is also extremely prevalent in northern Europe and represents the primary family of trees eliciting symptoms of allergy.
Alternaria is a mould which releases spores containing allergens in both internal and external environments. Damp internal environments are frequently associated with the growth of a variety of mould which can give rise to chronic symptoms of allergy and asthma. Intensive, seasonal release of spores give rise to airborne levels of allergen that can far exceed those achieved by pollen allergens such as grass and ragweed.
Japanese Cedar (known as Sugi) is the national tree of Japan. The average prevalence of Japanese cedar-pollen allergy in Japan is 26.5%. It causes classical symptoms of allergic rhinitis which can be very severe, from late February to early May.
These projects are in various stages of early research at McMaster University and in the case of Japanese Cedar also in Sagamihara, Japan.
Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease of unknown etiology affecting approximately 1% of the population. Anti-cyclic citrullinated peptide antibodies (ACPAs or anti-CCP) have been shown to be moderately sensitive and highly specific for the diagnosis of rheumatoid arthritis, and the appearance of ACPAs precedes development of RA by many years in some patients. Citrullination is a modification of protein involving the conversion of arginine residues to citrulline. In RA, citrullination of certain proteins present in joint tissues (eg. cartilage) may not only prompt the production of ACPAs, but also trigger a cellular immune response against the joint tissue itself. It is not known why citrullination occurs, nor the extent to which it is responsible for the symptoms experienced by RA sufferers. Adiga is therefore currently sponsoring research at McMaster University to understand the immune response and potentially relevant peptides derived from a number of proteins common to joint tissue, with the intention of designing a peptide vaccine against this debilitating condition.
The mechanisms of action of conventional immunotherapy are poorly understood. There are currently no reliable predictive biomarkers of clinical efficacy. There are however a wide range of relatively new technologies available that enable high throughput analysis of very complex samples, that can be combined with powerful computational analysis to reveal the changes that occur in physiological proteins and gene expression. These same tools can then be applied to the enhancing our understanding of the mechanism of action of therapeutic agents.
To this end Adiga, in collaboration with AllerGen, is currently conducting clinical studies aimed at identifying genetic and protein based biomarkers in cat allergic subjects treated with the cat allergy vaccine.