Translational drug discovery and development with the use of tissue-relevant biomarkers: Towards more physiological relevance and better prediction of clinical efficacy.

Due to the clinical development of drugs such as secukinumab, ustekinumab and dupilumab, major changes have been achieved in the treatment of patients diagnosed with psoriasis and atopic dermatitis. In academia and the pharmaceutical industry, research is increasingly moving towards the development of bispecific antibodies and multi-specific nanobodies, as there is a compelling need for new treatment modalities for patients suffering from autoimmune or malignant disease. The purpose of this review is to discuss aspects of translational drug development with a particular emphasis on indications such as psoriasis and atopic dermatitis. The identification of biomarkers, the assessment of target organ pharmacokinetic and pharmacodynamics interactions and a wide range of in vitro, ex vivo and in vivo models should contribute to an appropriate prediction of a biological effect in the clinical setting. As human biology may not be perfectly reflected by approaches such as skin equivalents or animal models, novel approaches such as the use of human skin and dermal microperfusion assays in healthy volunteers and patients appear both reasonable and mandatory. These models may indeed generate highly translationally relevant data that have the potential to reduce the failure rate of drugs currently undergoing clinical development.

24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain.

BACKGROUND: Collagen hydrolysate is a nutritional supplement that has been shown to exert an anabolic effect on cartilage tissue. Its administration appears beneficial in patients with osteoarthritis. OBJECTIVE: To investigate the effect of collagen hydrolysate on activity-related joint pain in athletes who are physically active and have no evidence of joint disease. DESIGN AND SETTING: A prospective, randomized, placebo-controlled, double-blind study was conducted at Penn State University in University Park, Pennsylvania. Parameters including joint pain, mobility, and inflammation were evaluated with the use of a visual analogue scale during a 24-week study phase. STUDY PARTICIPANTS: Between September 2005 and June 2006, 147 subjects who competed on a varsity team or a club sport were recruited. Data from 97 of 147 subjects could be statistically evaluated. INTERVENTION: One hundred and forty-seven subjects (72 male, 75 female) were randomly assigned to two groups: a group (n = 73) receiving 25 mL of a liquid formulation that contained 10 g of collagen hydrolysate (CH-Alpha) and a group (n = 74) receiving a placebo, which consisted of 25 mL of liquid that contained xanthan. MAIN OUTCOME MEASURES: The primary efficacy parameter was the change in the visual analogue scales from baseline during the study phase in relation to the parameters referring to pain, mobility, and inflammation. RESULTS: When data from all subjects (n = 97) were evaluated, six parameters showed statistically significant changes with the dietary supplement collagen hydrolysate (CH) compared with placebo: joint pain at rest, assessed by the physician (CH vs. placebo (-1.37 +/- 1.78 vs. -0.90 +/- 1.74 (p = 0.025)) and five parameters assessed by study participants: joint pain when walking (-1.11 +/- 1.98 vs. -0.46 +/- 1.63, p = 0.007), joint pain when standing (-0.97 +/- 1.92 vs. -0.43 +/- 1.74, p = 0.011), joint pain at rest (-0.81 +/- 1.77 vs. -0.39 +/- 1.56, p = 0.039), joint pain when carrying objects (-1.45 +/- 2.11 vs. -0.83 +/- 1.71, p = 0.014) and joint pain when lifting (-1.79 +/- 2.11 vs. -1.26 +/- 2.09, p = 0.018). When a subgroup analysis of subjects with knee arthralgia (n = 63) was performed, the difference between the effect of collagen hydrolysate vs. placebo was more pronounced. The parameter joint pain at rest, assessed by the physician, had a statistical significance level of p = 0.001 (-1.67 +/- 1.89 vs. -0.86 +/- 1.77), while the other five parameters based on the participants' assessments were also statistically significant: joint pain when walking (p = 0.003 (-1.38 +/- 2.12 vs. -0.54 +/- 1.65)), joint pain when standing (p = 0.015 (-1.17 +/- 2.06 vs. -0.50 +/- 1.68)), joint pain at rest with (p = 0.021 (-1.01 +/-1.92 vs. -0.47 +/- 1.63)), joint pain when running a straight line (p = 0.027 (-1.50 +/- 1.97 vs. -0.80 +/- 1.66)) and joint pain when changing direction (p = 0.026 (-1.87 +/- 2.18 vs. -1.20 +/- 2.10)). CONCLUSION: This was the first clinical trial of 24-weeks duration to show improvement of joint pain in athletes who were treated with the dietary supplement collagen hydrolysate. The results of this study have implications for the use of collagen hydrolysate to support joint health and possibly reduce the risk of joint deterioration in a high-risk group. Despite the study's size and limitations, the results suggest that athletes consuming collagen hydrolysate can reduce parameters (such as pain) that have a negative impact on athletic performance. Future studies are needed to support these findings.