Innate Immunotheraputics Limited

Autoimmunity

MIS416 re-regulation of autoimmunity

Autoimmune diseases arise following a breakdown in immunological tolerance mechanisms (self vs non-self discrimination) resulting in the development of a range of immunopathologies that may be associated with the presence of autoreactive antibodies, T cells, or general perpetual inflammation. Therapies which selectively manipulate cytokine and antibody production are therefore attractive clinical candidates, and several strategies for immunointervention are being developed around this conceptual framework.

MIS416 has key immunomodulatory properties that may have utility in the treatment of certain autoimmune diseases, in particular atopic disease, autoimmunity caused by viral infections, polyarteritis nodosa, and multiple sclerosis (MS):

  • Induction of soluble factors such as type I interferons, TGF-beta and IL-10 which may act at the level of immune deviation, regulatory T cell induction or inhibition of pro-inflammatory cytokines. The ability to induce these de novo may permit avoidance of systemic administration of cytokines and their severe side-effects.
  • Activation of NK and NKT cells which have long been suspected of playing an immunoregulatory role in the prevention of autoimmune diseases.
  • Demonstrable inhibition of serum Th2 cytokine levels following administration of a single i.v bolus in compassionate patient suffering from the Th2-type autoimmune disease polyarteritis nodosa (PAN). MIS also inhibits T cell proliferation in mixed lymphocyte reactions.
  • MIS does not induce a prolonged inflammatory cytokine storm and is not associated with direct activation of T or B cells. Mechanisms of MIS immunostimulation naturally involve an afferent phase associated with the transient production of a range of pro-inflammatory mediators such as TNF-alpha and IL-1 beta, whilst avoiding direct induction of high levels of Th1 activating cytokines such as IL-12p70. Since this occurs in concert with the natural induction of anti-inflammatory regulators prolonged pathological inflammation is not established.

MIS416 preclinical 'compassionate' treatment of progressive multiple sclerosis

MIS416 has been used preclinically to treat eight patients suffering from either 'primary progressive' or 'secondary progressive' MS. Use of an unapproved experimental medicine is permitted in New Zealand subject to the requirements of Sections 25 and 29 of the Medicines Act 1981. To date, the drug appears to have been safe and well tolerated by these patients and in the secondary progressive MS patients, there have been self-reported improvements in some of the signs and symptoms associated with disease.

The results from this unregulated and uncontrolled use of the experimental and unapproved MIS416 are anecdotal and can not be relied upon as part of the formal drug approval process. However the apparent safety and possible therapeutic outcomes to date have been such that Innate Immunotherapeutics has selected progressive MS as the initial clinical development target and formal studies commenced in October 2010. See 'Clinical Trials'.