Enzyme blockers could be new psoriasis treatment
inhibit enzymes known as metalloproteinases have the hallmarks of a
new treatment for the common skin diseases psoriasis.
They suggest that the finding could lead to the development of a new class of drugs that inhibit the uncontrolled cell division that underlies the diseases with few side effects.
Cell biologists of the University of Bonn in Germany, in cooperation with researchers at the University of Leeds in the UK and from industry, found that inhibitors of metalloproteinases can normalise the increased tendency of the skin cells involved in psoriasis (keratinocytes) to divide. They report their findings in the Journal of Investigative Dermatology (Vol 123, No 3).
In psoriasis, the regeneration of the epidermal layer of the skin is speeded up enormously: whereas it normally renews itself in just under four weeks, this period is cut to four to seven days. The reason is the greatly increased rate of cell division of the keratinocytes. These cells form a layer which separates the epidermis from the dermis, which lies beneath it. The ageing cells pass from this germinal layer to the surface until they finally scale off.
No side effects ?
The target of the new treatment - the enzyme which stimulates the division of the keratinocytes - is the protein sAPPa. It is produced during the decomposition of a larger protein, APP or amyloid precursor protein.
The keratinocytes produce an enzyme - alpha secretase - which cuts the APP down to size as sAPPa. After adding inhibitors, the team observed that the discharge of sAPPa was almost completely arrested in the cells of psoriasis patients. As a result, the greatly increased division rate of the keratinocytes dropped back to normal values, a reduction of 50 to 60 per cent,' commented Christina Siemes, a member of the research team.
"We have been able to confirm this in skin specimens of five psoriasis patients," she noted.
The inhibiting effect of the metalloproteinase inhibitors largely wore off within 72 hours, and this bodes well for the likely dosing of a drug based on the treatment. Moreover, even with fivefold concentration of the active ingredient the research team could not detect any side effects.
For example, other aspects such as the number of skin cells which entered into apoptosis - a phenomenon known as programmed cell death which seems to occur when the body elects to destroy a damaged cell - remained constant. Cellular protein synthesis also appeared to be unaffected.
The research raises hopes of a new treatment for psoriasis, although the researchers stress that it tackles one of the primary symptoms of the disease, and does not address the underlying immune reaction.
The researchers now intend to test their method on animals, using naked mice on which they have transplanted the skin tissue of psoriasis patients. They want to apply the active ingredients locally as ointment. In addition, the first tests on human beings are planned in the near future.
