Hair Genesis New Generation IV

Hair Loss Clinical Studies - Latest Research

Novel Hair Loss Formula Demonstrates Anti-inflammatory Activity in vitro

From : Chittur S., Parr B., and Marcovici G., Inhibition of Inflammatory Gene Expression in Keratinocytes Using a Composition Containing Carnitine, Thioctic Acid and Saw Palmetto Extract. Medicine- Evidence Based Complementary and Alternative Medicine:  http://ecam.oxfordjournals.org/cgi/content/full/nep102

          Currently, the typical drug-based regimen for pattern hair loss is either minoxidil and/or finasteride -- or possibly dutasteride.   A caveat with all current drug-based options is the potential for negative side effects.  Alternatively, in the past few years a series of naturally-based hair loss treatments have been developed containing active compounds and phytochemicals.  These generally offer an excellent safety profile, however, with rare exception, they remain largely unsupported by peer-reviewed data. 

          The development of safe and highly effective treatments for pattern hair loss thus remains a challenging goal.   While the genetic basis of androgenetic alopecia (AGA) has not yet been completely determined, it is clearly a complex genetic disorder in which multiple genes, hormonal pathways and environmental factors contribute to  phenotype.  To date, DHT modulation via 5-AR blockade remains the main target for medical therapy shown to slow the progression of AGA. 

          Previously, in a small IRB-monitored trial, we tested the efficacy of the liposterolic extract of Serenoa repens (LSESr), aka saw palmetto extract, aka Permixon and its glycoside, β-sitosterol, in subjects with AGA and showed a highly positive response to treatment.  The resulting publication in 2002 (1)  established the effectiveness of naturally occurring 5-AR inhibitors against AGA for the first time.     LSESr, sourced from the fruit of the saw palmetto tree contains a veritable stew of bioactive fatty acids and sterols, including stigmasterol, campesterol, and β-sitosterol.  

          Saw palmetto first came into widespread clinical use in Europe as a demonstrably safe and effective treatment for benign prostatic hyperplasia (BPH) (2). Notably, in a direct comparison of LSESr against finasteride, it was reported that LSESr exhibited a 3-fold greater inhibition of 5-AR in in vitro assays (3).  But clearly blockade of 5-AR treats only one aspect of AGA.  Chronic inflammation is recognized at the molecular and cellular levels as the final common pathway of many systemic and degenerative diseases, including those affecting skin.  It has also been observed that inflammation plays a role as a contributing factor to common pattern hair loss.  Histologically, sustained follicular inflammation is a known finding in AGA.  

          In our most recent study, we sought to test a proprietary formulation containing LSESr, L-carnitine and thioctic acid (TA) in a well-validated in vitro assay representative of HF keratinocytes, specifically, LPS-stimulated HaCaT cells.  Our rationale was based on the understanding that L-carnitine, TA and LSESr operate through distinct, but potentially interrelated, biochemical and molecular mechanisms.  For instance, accumulating evidence suggests that L-carnitine may play a significant role in prevention and treatment of numerous diseases as well as protection from accelerated aging that result from oxygen free-radical damage, inflammation and glycation (non-enzymatic glycosylation).

          One line of research suggests that carnitine may possess the ability to promote hair growth in vitro by increasing energy supply to the rapidly proliferating and energy-consuming anagen hair matrix (4).  Likewise, TA is now recognized as a compound with many biological functions, such as the modulation of pathogenic inflammatory events, including those in the skin.   Thus, our hypothesis hinges on the enhanced efficacy of combining targeted anti-inflammatory agents with 5-AR inhibitors. 

          Here, we assayed for changes in gene expression across a spectrum of well-characterized inflammatory markers and found that our test compound demonstrates statistically significant anti-inflammatory properties in vitro.  For example, we noted that the composition effectively suppressed LPS-activated gene expression of chemokines CCL17, CXCL6 and Leucotriene( LT)B4. The over-expression of each of these markers has previously been observed in the setting of inflammation and apoptosis.

          Recognizing that inflammation contributes to a wide range of diseases, including those affecting the skin and hair, it is our view that the blockade of inflammation in susceptible hair follicles represents a new and potentially viable therapeutic avenue.  Since the clinical success rate for treatment of AGA with androgen blockade alone is limited, there is enormous unmet medical need for patients who are refractory to current therapy

See Hair Genesis Study 1

See Hair Genesis Study 2

References

1.         Prager N, Bickett K, French N, Marcovici G. A randomized,

            double-blind, placebo-contolled trial to determine the effectiveness

            of botanically derived inhibitors of 5-alpha-reductase in the treatment

            of androgenetic alopecia. J Altern Complement Med 2002;8:

            143–52.

2.         Plosker GL, Brogden RN. Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Drugs Aging ( 1996;) 9:: 379–95.

3.         Délos S, Iehlé C, Martin PM, Raynaud J. Inhibition of the activity of ‘basic’  alpha- reductase (type 1) detected in DU 145 cells and expressed in insect cells. J Steroid Biochem Mol Biol ( 1994;) 48:: 347–52

4.          Foitzik K, Hoting E, Förster T, Pertile P, Paus R. L-carnitine-L-tartrate promotes human hair growth in vitro. Exp Dermatol ( 2007;) 16:: 936–45.

Dr. Marcovici is Chief Scientific Officer of Advanced Restoration Technologies Inc. (ART).  He was involved in the development of wound healing methodology now in widespread medical use worldwide (e.g., Procyte’s copper based tripeptide product Tricomin™ & Organogenesis’ epithelial barrier function agonist Apligraf™).  From 2000 to present, ART has limited its research focus solely to the creation of safe and empirically tested hair loss treatment formulations.