5 research outputs found
On the selectivity of 5-aminolevulinic acid-induced protoporphyrin IX formation
Due to its capability to induce accumulation of protoporphyrin IX (PpIX) selectively in a multitude of different pathologies, 5-aminolevulinic acid (ALA) and its derivatives have attracted enormous attention in the field of photodynamic therapy (PDT) in the past two decades. The photochemical and photophysical properties of PpIX have been used for the fluorescence photodetection and photodynamic treatment of neoplasms in several medical indications in which conversion of ALA into PpIX seems to take place preferentially. Recently, this has led to the approval of this therapy for the treatment of actinic keratosis and basal cell carcinoma. When applied topically or systemically, ALA bypasses the negative feedback control that haem exerts on the enzyme ALA synthase (ALAS), which catalyses the natural production of this delta-amino acid, thereby temporarily boosting the generation of PpIX, the direct precursor of haem. Despite considerable interest in this treatment methodology, only little is known concerning the reasons for the selective accumulation of PpIX in neoplastic tissue upon ALA administration. Following an introduction into the biochemical as well as the chemical principles of haem synthesis, the present review tries to summarise experimental evidences of the mechanisms underlying preferential production of PpIX in neoplastic tissues. Thereby, morphological, environmental, enzymatic, as well as cell-specific factors will be discussed
Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease
Guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: Consensus of a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)
Objectives:To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need.Methods:The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO).Results:This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis.Conclusions:While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA
Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease
peer reviewedThe European Society for Clinical and Economic Aspects
of Osteoporosis, Osteoarthritis and Musculoskeletal
Diseases convened a task force of experts in rheumatoid
arthritis (RA) and clinical trial methodology to comment
on the new draft ‘Guideline on clinical investigation of
medicinal products for the treatment of RA’ released by
the European Medicines Agency (EMA). Special
emphasis was placed by the group on the development
of new drugs for the treatment of early RA. In the
absence of a clear definition of early RA, it was
suggested that clinical investigations in this condition
were conducted in disease-modifying antirheumatic
drugs naïve patients with no more than 1 year disease
duration. The expert group recommended using an
appropriate improvement in disease activity (American
College of Rheumatology (ACR) or Simplified/Clinical
Disease Activity Index (SDAI/CDAI) response criteria) or
low disease activity (by any score) as primary endpoints,
with ACR/European League Against Rheumatism
remission as a secondary endpoint. Finally, as compelling
evidence showed that the Disease Acrivity Score using
28-joint counts (DAS28) might not provide a reliable
definition of remission, or sometimes even low disease
activity, the group suggested replacing DAS28 as a
measurement instrument to evaluate disease activity in
RA clinical trials. Proposed alternatives included SDAI,
CDAI and Boolean criteria