Dermatology Clinical Indications
Acne
 Acne is a pleomorphic disease caused by an interaction between hormones, skin oils, and bacteria which causes inflammation of sebaceous glands. Well characterized etiologic factors include increased sebum production, ductal hyperkeratosis, and abnormality of the microbial flora within the pilosebaceous unit and release of inflammatory mediators. Sebaceous glands are stimulated by increased hormone levels, especially the androgens which are known to cause excessive sebum production levels.
The Research and Development of developing ASC-J9® into an Acne indication was supported, from 2004 to 2008, by a Phase I and a Phase II SBIR grant from the Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institute of Health. These government grants have helped and moved this project forward to test human acne patients in clinical trials in 2008.The phase II clinical study results provided evidence that ASC-J9® in a cream formulation imparts a therapeutic effect in lowering lesion counts in moderate to severe acne, with the highest dose group demonstrating the largest percent reductions from baseline at week 12 in inflammatory lesion count and total lesion count. To date we have also developed a new formulation that absorbs the active ingredient (ASC-J9®) more readily into the dermis, indicating the new cream preparation will show even greater efficacy in future clinical trials. No side effects have been noted in either phase I or phase II clinical trials.
In early 2011 ASC initiated a Phase IIb clinical study to evaluate the safety and efficacy of topical 0.1% and 0.025% ASC-J9 creams applied twice daily for facial acne. Approximately 180 patients at least 12 years of age with facial acne will be randomized to twice daily topical treatment with 0.1% or 0.025% ASC-J9 cream or vehicle control for 12 weeks.
For further information and if you are an acne patient interested in enrolling, please refer to the following link to the NIH clinical trials global website: http://clinicaltrials.gov/ct2/show/NCT01289574?term=ASC-J9&rank=1
Potential advantages of using ARD enhancer, ASC-J9®, to treat Acne:
- ARD enhancer acts on the major cause of acne to directly reduce the high level of AR in sebaceous glands and lower sebum secretion, an approach different from current acne treatments which treat symptoms of the disease such as to unplug the blocked follicular pores, bacteria infection and subsequence inflammation.
- The mechanism of AR degradation make ARD enhancer more effective than conventional anti-androgens (which need to compete with systemic and local androgens) in attenuating endogenous androgens, especially the elevated skin androgens and over-expressed AR, to activate sebaceous glands. No conventional anti-androgens have been developed into a topical drug for acne.
Alopecia
A model for the pathogenesis of androgenetic alopecia referred to as “male pattern baldness” include the miniaturization of the hair follicle and an increase in the ratio of telogen to anagen hairs,  the systemic and local effects of androgens in promoting the condition, and the genetically inherited tendency. Studies in patients with androgen insensitivity syndromes have suggested that androgenetic alopecia is induced by activation of follicular AR by dihydrotestosterone (DHT). Intrafollicular androgen overactivity may be due to the combination of local factors such as increased numbers of AR, increased local production of DHT, and to systemic factors such as increased circulating androgens providing increased substrate for conversion to dihydrotestosterone
AndroScience currently has approval to commence a phase II clinical trial in androgenetic alopecia using the ASC-J9® compound. A foam formulation has been developed for alopecia and the company is positioning clinical trial resources and investigative sites to begin the trial towards the end of 2009.
Potential advantages of using ASC-J9® as drug to treat Androgenetic Alopecia:
- ARD enhancer acts on the cause of androgenetic alopecia to reduce AR, and prevent androgen from acting on hair follicles.
- ARD enhancer induce AR degradation and would therefore be more effective than conventional anti-androgens such as Finasteride, which only reduces DHT but not testosterone or other factors that are known to bind to and activate AR.
Wound Healing
Androgens are known to be involved in inflammation, which leads to a delay in wound healing, especially in diabetic patients and aging men. Impaired wound healing in the elderly men leads to substantial morbidity, mortality, and a cost to the US Health Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked gender differences in wound repair. Several studies have shown that castration of male mice results in a striking acceleration of local cutaneous wound healing associated with a reduced inflammatory response.
We have demonstrated that artificial wounds created in animals that lack AR function (AR knock-out mice) heal faster vs. wild type mice that carry functional AR. Preliminary data has been generated showing that topically applied ASC-J9® cream to artificially created wounds in normal mice skin hastens the wound healing process.
ANDROGEN RECEPTOR DEGRADATION ENHANCER PROGRAMS (ARD ENHANCERS): ASC-J9, ASC-JM
Novel First in Class Mechanism of Action, Wide Pharmacological Applications
- Dermatology ARD Enhancer Clinical Efficacy & Safety
- Achieves greater efficacy through;
- Lower androgen mediated sebaceous gland hyperplasia and inflammation in acne; and prevent androgen from acting on hair follicles in alopecia.
- Topically applied – lacking systemic absorption leads to fewer expected side effects and potential for both male and female patients
- Role in combination therapy with other non-androgen acne drugs
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