Long Term Remissions in Psoriasis with Protocol Aimed at Inhibiting Phosphorylase Kinase

The genetic defect in psoriatic individuals is present at birth, but the disease is manifested only when precipitated by various injurious stimuli. Including trauma, contact allergens and bacterial superinfection.  Among the earliest molecules expressed after injury is the enzyme, phosphorylase kinase (PhK), which is released 5 mins following injury.  Elevated PhK activity is observed in both involved and uninvolved skin of active psoriasis, correlating with increased PCNA (proliferating cell nuclear antigen) expression, presence of parakeratosis and psoriatic hyperproliferation.  Suppression of PhK with its inhibitor, topical curcumin, resulted in de-expression of PCNA, resolution of parakeratosis and psoriatic hyperproliferation, with resolution of clinical psoriasis (Heng MCY et al. Br J Dermatol 1994; 130:298-306; Heng MCY et al. Br J Dermatol 2000; 143:937-939).

The PhK  molecule is a tetramer of four subunits (α,β,γ,δ).  The δ subunit (calmodulin) is a calcium binding protein activated by contact allergens and bacterial superantigens. The α and β subunits respectively are involved in activation and deactivation of PhK, when their receptors are bound by the respective ligands (Type I and II cAMP dependent protein kinases).  

Genetic Susceptibility

Genes for psoriatic familial susceptibility and psoriatic susceptibility loci have been mapped to 17q and 16q and 17q respectively, corresponding to the β subunit (16q) (contains receptor), and Type II cAMP protein kinase (17q) (ligand), which form the switch-off mechanism for PhK activity. This supports the hypothesis that a defective switch-off mechanism for PhK may be present in psoriasis.  

Hypothesis and Protocol

Based on this hypothesis, a protocol was developed for the treatment of psoriasis using topical curcumin, a  selective, non-competitive phosphorylase kinase inhibitor to inhibit the elevated phosphorylase kinase activity, avoidance of contact allergens (black hair and clothing dyes, elastic/latex/spandex clothing and stockings, trivalent products including leather and gasoline, and nickel from coins and keys and jewelry) that activate the calmodulin-containing δ subunit, treatment of bacterial superfection (Staphylococcus aureus and MRSA, Streptococcal infection), fungal and viral infections.  Topical steroid preparations are also used since they have anti-TNFα effects.  

This protocol was used in a prospective study of 647 consecutive patients over 7 years, and achieved complete clearance of psoriasis in 72.2% of patients within 16 weeks. Of these, 60% were able to achieve long-term remission of their psoriasis  even after withdrawal of all treatment.