PDC41 Series for primary dysmenorrhea

Scientific publications
Primary dysmenorrhea is a disabling condition found in approx. 10-15% of women of childbearing age (Smith and Barbieri, 2005). Pain is caused by frequent and prolonged uterine contractions that decrease blood flow to the myometrium resulting in ischemia. This painful women's health condition has been estimated to account for 600 million lost work hours and $2 billion in lost productivity annually in the US alone (Coco, 1999).

Excessive concentrations of PGF2α are implicated in the uterine hypercontractility associated with primary dysmenorrhea. During menstruation arachadonic acid stored in the endometrium is converted to PGF2α , prostaglandin E2 (PGE2) and leukotrienes. The release of prostaglandins from the endometrium at the time of menses induces uterine smooth muscle contractions which manifest as labour-like lower abdominal and back pain. In primary dysmenorrhea, excess production of endometrial PGF2α or an elevated PGF2α :PGE2 ratio has been reported. In women with primary dysmenorrhea uterine contractions can last several minutes and may produce uterine pressures of greater than 400mmHg, five times greater than resting pressures (Banikarim, 2006; Sales and Jabbour, 2003).

The key role of prostaglandins in primary dysmenorrhea underpins the current use of NSAIDS as first-line treatment for this condition, the most commonly used of which are naproxen and ibuprofen. NSAIDs are typically started at the onset of menses and continued for the initial one to two days of the menstrual cycle, or for the usual duration of 'crampy' pain. However, NSAIDs are associated with significant gastrointestinal toxicity and carry the risk of cardiovascular and renal toxicities as well. In addition, because they work indirectly by inhibiting prostaglandin synthesis, they do not provide immediate relief of symptoms.

PDC41 Series for primary dysmenorrhea

The company intends to develop non-intravenous (non-IV) formulations of PDC31, termed "the PDC41 Series" which would be self-administered by women suffering from the pain due to excessive uterine contractility associated with primary dysmenorrhea. Various formulations have been successfully employed with peptides, including nasal, sublingual, pulmonary, vaginal or rectal suppositories. The PDC41 Series will focus initially on the development of a nasal formulation (PDC411). Selectively blocking PGF2α is expected to provide a better safety profile than NSAIDs, with a more rapid onset of action, and therefore more immediate relief of symptoms. Unlike NSAIDs which broadly inhibit prostaglandin synthesis in all tissues, compounds in the PDC41 Series are not expected to cause gastrointestinal, cardiovascular or renal toxicities.

References

  • Smith RP and Barbieri RL Primary dysmenorrhea in adults, Official topic review from UpToDateŽ, 2006.
  • Sales KJ and Jabbour HN. Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium. Reproduction 2003;126:559-567.
  • Banikarim, C. Primary dysmenorrhea in adolescents Official topic review from UpToDateŽ, 2006.