A new gene has been revealed by a research team from the Columbia University Medical Center (NY, USA) that determines human hair texture. The team discovered that mutations in the P2RY5 gene resulted in ‘wooly hair’, which is coarse, dry, sparse, tightly curled and hereditary.
“Our findings indicate that mutations in the P2RY5 gene cause hereditary woolly hair. This is significant as it represents the discovery of the first new gene whose primary function seems to be the determination of hair texture in humans,” explains lead author Angela M Christiano, Columbia University College of Physicians and Surgeons (NY, USA). She adds, “this genetic finding may inform the development of new treatments for excessive or unwanted hair, or potentially hair growth.”
Christiano and colleagues focused their research on Pakistani individuals as previous research had demonstrated that wooly hair was common among Pakistani families. The team performed a genetic analysis of six families with hereditary wooly hair, all of whom were of Pakistani origin. The discovery that hereditary wooly hair arose from a P2RY5 mutation was the first discovery towards suggesting the pathogeneisis of this condition.
Christiano’s discoveries have resulted in the identification of several genes that control human hair growth. It has not yet been determined whether other variants in hair texture between various human populations can be attributed to variants of the P2RY5 gene
This is the first G-protein-coupled receptor gene that has been associated with human hair disorders and it is hoped that this discovery will lead to drug development to target this receptor.
Source: Shimomura Y, Wajid M, Ishii Y et al. Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat. Genet. 40(3), 335–339 (2008).
Alternative psoriasis treatment may be no better than placebo
The Indian spice tumeric has proved a popular alternative treatment for psoriasis but a report this month revealed that the only beneficial effects observed after ingesting the spice could be caused by the placebo effect.
The research was conducted at the University of Pennsylvania School of Medicine (PA, USA) and was published in the Journal of the American Academy of Dermatology. The study authors found that curcumin, which is the active ingredient in turmeric, produced such a low positive response that it could be attributed to the placebo effect. There has been strong evidence to suggest that curcumin inhibits a critical pathway of psoriasis and so these findings are disappointing for those looking for a safe, inexpensive and effective alternative therapy.
Joel Gelfand, one of the authors from the study explains, “alternative and complementary websites and newspapers publish anecdotal reports that the Indian spice has been successfully used to treat psoriasis. However, spontaneous improvements in psoriasis are common, and based on our study, until larger, placebo-controlled trials are conducted, oral curcumin should not be recommended for the treatment of psoriasis given lack of proven efficacy.”
The researchers conducted a Phase II, open-label, Simon’s two-stage trial of oral curcuminoid C3 complex in plaque psoriasis patients administered at 4.5 g/day. End points were considered to be improvement in Physicians Global Assessment score, Psoriasis Area and Severity Index score and safety end points.
The authors admit that the small study size (12 patients) limited the study, as did the lack of placebo group for comparison. The authors do not completely discount the potential of the spice but believe more research is needed, and more positive outcomes must be observed before it can be considered an effective alternative treatment.
Many patients are turning to alternative treatments owing to the cost and limitations of current approved treatments, such as the risk of infections and possible malignancies from long-term use.
Excellent positive responses were observed in the two of the patients but, overall, the results were not sufficient to begin recommending the spice as an effective treatment, although it may be effective in a small subset of psoriasis patients. “What is needed is scientific data to assess the safety and efficacy of these treatments so that we may more rationally inform patients of their treatment options,” concludes Gelfand.
Source: Kurd SK, Smith N, Vanvoorhees A. Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: a prospective clinical trial. J. Am. Acad. Dermatol. (2008) (Epub ahead of print).
Insight into mechanism of acne drug
Although 13-cis retinoic acid (13-cis RA, also known as isotretinoin and accutane) is the most potent available drug for acne, it’s mechanism has been poorly understood until recently. Diane Thiboutot and colleagues (Pennsylvania State University College of Medicine, PA, USA) have provided mechanistic insight by analyzing patients’ skin biopsies before and 1 week after treatment with 13-cis RA using transcriptional profiling.
The drug has been associated with severe side effects and insight into its mechanism could lead to new treatments for acne that are as effective as 13-cis RA.
The tests conducted by Thiboutot and colleagues, including the biopsies of seven patients, confirmed that the drug works by inducing apoptosis in sebaceous glands by TdT-mediated biotin 16-dUTP nick-end labeling (TUNEL) staining, which had been previously observed in prior studies. They then observed that lipocalin 2 was one of the genes that was the most upregulated by 13-cis RA. Lipocalin 2 encodes neutrophil gelatinase-associated lipocalin (NGAL), which is known to function in innate immune defense and induces apoptosis of B lymphocytes in mice.
Further studies revealed that the gene responsible for making the protein NGAL was highly upregulated in human sebaceous glands by 13-cis RA. As NGAL was found to mediate apoptosis of human sebaceous glands and to be essential for 13-cis RA-mediated apoptosis of human sebaceous glands, the authors suggested that agents that selectively induce NGAL expression in human sebaceous glands might provide a new approach to treating individuals with acne.
Following treatment with 13-cis RA, it was noted that the sebaceous gland demonstrated increased immunolocalization, in addition to recombinant NGAL-induced apoptosis in SEB-1 sebocytes. In addition, apoptosis in response to 13-cis RA was inhibited in the presence of siRNA to lipocalin 2.
The authors concluded that the results indicate that NGAL mediates the apoptotic effect of 13-cis RA and that possible alternatives to 13-cis RA for acne treatment could be developed that selectively induce NGAL expression in sebaceous glands.
Source: Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells. J. Clin. Invest. (2008) (Epub ahead of print).
DNA vaccine candidate for melanoma reaches final stage of Phase I clinical trial
Vaccine: TriGrid™ electroporation system
Manufacturer: Ichor Medical Systems
Indication: Melanoma
Stage of development: Phase I clinical trial
Melanoma patients are being recruited for the final stage of a Phase I clinical trial using a DNA vaccine delivered by the TriGrid™ electroporation system (Ichor Medical Systems, CA, USA). The vaccine contains DNA encoding a type of tyrosinase, which is a common protein found in melanoma cells and is a target for vaccination. The DNA vaccine was developed by researchers at the Memorial Sloan-Kettering Cancer Center (NY, USA).
“We believe that the immune system can be trained to recognize cancer as something that is foreign and dangerous. But delivering enough of the DNA vaccine into cells so that the encoded antigen can be produced in sufficient amounts to cause an immune response has been a significant challenge,” said the study’s principal investigator Jedd Wolchok, a medical oncologist at Memorial Sloan-Kettering.
DNA vaccines must be delivered inside the target cells, where the DNA can be expressed into antigens and immune responses can be triggered. Electroporation utilizes a low-voltage electric current to create a temporary opening on the cell surface, through which DNA can enter. Ichor’s TriGrid system has been shown to increase the DNA delivery efficacy over 100-times compared with other methods.
In the earlier stage of the trial, the melanoma DNA vaccine was delivered with TriGrid electroporation five-times over 15 weeks to six patients, three at the low dose and three at the medium dose. The highest dose of the vaccine will be tested in this final stage of the trial.
“We are delighted to be collaborating with Memorial Sloan-Kettering’s prestigious team,” said Ichor’s chief executive officer Bob Bernard. “DNA-based vaccines hold tremendous promise to treat numerous serious diseases. We are hopeful that results of this and other studies now in progress will show the TriGrid to be an enabling platform for the entire field of DNA-based vaccines.”
Source: Ichor Medical Systems, Inc.: www.ichorms.com; Memorial Sloan-Kettering Cancer Center: www.mskcc.org
Head lice resistant to standard treatment may be eradicated by ivermectin
Ivermectin has been found to be 100% effective in killing head lice that are resistant to most standard treatments, researchers from the University of Massachusetts (MA, USA) Amherst revealed. The compound is usually used in the treatment of plant parasites and intestinal worms. Head lice are increasingly becoming a problem to the estimated 12 million people that they effect in the USA alone, due to the growing resistance they are showing to commonly used treatments.
Over the past two decades, lice have been beginning to show resistance to pyrethrum, a botanical insecticide, which is the active ingredient in most treatments for head lice. “The arsenal of medications used to treat head lice is limited and shrinking, and health providers are spending an increasing amount of time and resources dealing with infestations,” says J Marshall Clark, one of the study authors. He adds, “this has created a demand for new treatments that are effective and safe to use on children.”
The research group used ivermectin in a formulation, which included water, olive oil and shea butter in its ingredients. The topical preparation was used on permethrin-resistant lice that had been collected from school children in southern Florida. The compound ivermectin is produced by bacteria and is usually used against worms, mites and plant parasites, which it eradicates by attacking the nervous system and muscles.
The researchers applied formulations of the ivermectin mixture to lice in strengths of 1.0, 0.5 and 0.25%. All three solutions were found to be 100% effective in killing newly hatched lice within 10 min of exposure. Interestingly, the formulations were found to be more effective than directly applying 0.5% ivermectin alone, suggesting that the topical formula allowed for increased penetration into the lice.
The high efficacy will mean that children will no longer have to endure multiple applications of treatment to eradicate the problem. In addition, ivermectin is not absorbed well through the skin, making it an ideal topical application. Further studies are required to elucidate whether the formulation will be as effective on unhatched lice eggs. It is expected that it will take approximately 2–3 years for full US FDA approval.
Source: Strycharz JP, Yoon KS, Clark JM. A new ivermectin formulation topically kills permethrin-resistant human head lice (Anoplura: Pediculidae). J. Med. Entomol. 45(1), 75–81 (2008).