A cold sore cure has become a greater possibility after scientists elucidated how the herpes simplex virus can lie dormant for prolonged periods.
Scientists at Duke University Medical Center (NC, USA) have come closer to discovering a cure for cold sores by working out how the virus remains inactive.
The disease is caused by the herpes simplex virus (HSV)1, which lies dormant in the trigeminal nerve until it’s triggered by stress, fever or excess sunlight and a cold sore outbreak occurs.
“We have provided a molecular understanding of how HSV1 hides and then switches back and forth between the latent (hidden) and active phases,” explains author Brian Cullen of the Duke University research group.
These findings will also have an impact on the understanding of other latent diseases, such as shingles and HSV2.
HSV1 can remain dormant for years and while it is so it cannot be treated and does not replicate itself. It does however produce a molecular product known as latency associated transcript (LAT) RNA.
“It has always been a mystery what this product, LAT RNA, does,” adds Cullen. “Usually viral RNAs exist to make proteins that are of use to the virus, but this LAT RNA is extremely unstable and does not make any proteins.”
The team have found that LAT RNA, when processed into smaller miRNAs, blocks the production of proteins responsible for the virus to initiate active replication. Stress triggers the virus to produce higher amounts of mRNAs and the amount of miRNAs are then insufficient to block replication.
Once replication begins to occur, the virus travels down the trigeminal nerve to the initial site of infection and a cold sore erupts. Cullen explains that these new findings can help to find a way of bringing the virus out of its dormant phase and then tha patient could be treated with a drug to combat the virus.
“In principle, you could activate and then kill all of the virus in a patient,” explains Cullen. “This would completely cure a person, and you would never get another cold sore.”
The team are now working on a way to develop a drug to combat cold sores using their recent findings.
Source: Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature DOI: 10.1038/nature07103 (2008) (Epub ahead of print).
Environmental Working Group claims that many sunscreens are ineffective or hazardous to health
A US nonprofit group have made claims that most sunscreens are either ineffective or hazardous to health, following an investigation on almost 1000 brand-named sunscreens. The sunscreen industry dispute the claims made by the Environmental Working Group (EWG) who claim that four out of five of the sunscreens they looked at didn’t protect against UV radiation or contained chemicals that were potentially hazardous.
The EWG published their findings on their website in a report entitled “Sunscreen Summary – What Works and What’s Safe”. According to the report, Coppertone (Scherring-Plough), Banana Boat and Neutrogena (Johnson & Johnson) products demonstrated the worst results.
The main criticism by the EWG was that many claims on the product’s packaging, such as ‘high SPF’, ‘broad spectrum protection’ and claims that the product was ‘waterproof’ appeared to not be met.
In total, 952 sunscreens were investigated and, of these, only 143 products offered protection from the sun that was deemed to be ‘very good’, using ingredients that posed minimum risks to health.
The EWG also found that of Coppertone’s 41 sunscreen products investigated, none met the EWG’s safety and effectiveness standard. In addition, of the 103 Banana Boat and Neutrogena products looked at, only one product met this standard. The criteria for a product meeting the EWG’s safety and effectiveness standard was a product that blocked both UVA and UVB radiation, contained either no or very few chemicals that were known to be hazardous to health and remained stable in sunlight. Only 15% of products tested met these standards.
Spokespersons for Schering-Plough, Johnson & Johnson and Banana Boat disputed the claims and highlighted the fact that their products underwent rigorous independent testing.
Source: Skin Deep cosmetic safety database www.cosmeticsdatabase.com/special/sunscreens2008/index.php
Ustekinumab may be effective for treating psoriasis
Trial name: PHOENIX2
Drug: Ustekinumab
Patients enrolled: 1230
Trial: Phase III, multicenter, double-blind, placebocontrolled
Recent results from a series of Phase III trials, demonstrating the efficacy of ustekinumab (CNTO 1275) for patients suffering moderate-to-severe psoriasis have been published in the Lancet, illustrating that the drug maintains its efficacy when administered every 12 weeks. This is a favorable regimen to follow for both patients and physicians.
The drug is a human anti-IL-12 and -23 monoclonal antibody and is under development by Centrocor (a subsidiary of Johnson & Johnson).
The recent PHOENIX 2 study assessed the drug’s efficacy and safety whilst also determining dosing intensification in partial responders to the drug.
A total of 1230 patients took part in this multicenter, Phase III, double-blind, placebo-controlled study. All patients suffered from moderate-to-severe psoriasis (defined as having a minimum of 10% total body surface area involvement and psoriasis area and severity index [PASI] of 12 or above).
Each participant was assigned randomly to receive either placebo or ustekinumab in either a 45 or 90 mg dose at 0 and 4 weeks and then every 12 weeks. Partial responders (those achieving between 50 and 75% improvement in PASI scores) were then re-randomized to receive doses either every further 12 weeks or every 8 weeks.
The primary end point was considered to be patients achieving a 75% improvement in PASI scores at week 12. Of those receiving ustekinumab at 45 mg doses, 66.7% achived the primary endpoint. Of those that received the drug at 90 mg doses, 75.7% reached the primary end point. Of those receiving placebo, only 3.7% achieved the primary end point.
The partial responders receiving 90 mg doses responded better when the dosing frequency was increased to administration every 8 weeks (66.8 vs 33.3% of patients achieving 75% PASI score improvement when receiving doses at 8 and 12 weeks, respectively). No difference was observed in results with increased dosing intensity in the group of partial responders receiving 45 mg doses.
The results highlight that for most patients, a dosing frequency of every 12 weeks is sufficient to significantly improve moderate-to-severe psoriasis and that for partial responders an increase in dosing frequency to every 8 weeks at 90 mg should be achieved.
These results were published alongside the results of the PHOENIX 1 trial that indicated that ustekinumab appears to be efficacious in treating most patients with moderate-to-severe psoriasis and that dosing administration every 12 weeks would maintain efficacy for at least 1 year.
Source: Papp KA, Langley RG, Lebwohl M et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 371(9625), 1675–1684 (2008).
Owning a cat may increase eczema risk in children with filaggrin deficiency
A recent study has suggested that the risk of a child developing eczema in their first year is increased if they have a specific gene mutation in the protein filaggrin (FLG) and they are exposed to a cat.
It had previously been demonstrated that two common variants in the gene encoding FLG causes a predisposition to eczema. FLG acts as a physical barrier to harmful substances and therefore provides a protective function.
Hans Bisgaard, (University Hospital Gentofte, Copenhagen, Denmark), and his team suggested that the physical barrier of the skin was weakened with the loss of these genes and they set out to investigate this hypothesis. They performed a cohort study on 379 infants born to mothers with asthma and a further 503 infants born to women in the general population. The children were assessed for variants of FLG to ascertain whether they had one or two defective copies of FLG. In addition, the families were asked whether they had a cat or dog in the household.
Children in both of the two groups demonstrated that the likelihood of developing eczema in the first year of life was increased twofold in infants with FLG mutations. This risk was further increased when a cat was owned by the children’s family at the infant’s birth. No increased risk was observed with dog ownership.
The researchers believe that a deficiency of FLG weakens the skin’s barrier but it remains unclear why an exposure to cats further perpetuates eczema development in some individuals. These results suggest that children deficient in FLG should avoid contact with cats in early life.
Source: Bisgaard H, Simpson A, Palmer CN et al. Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med. 5(6), e131 (2008).
Clones of patient’s killer T cells may lead to complete remission in advanced melanoma patients
A remarkable case of a 52-year-old melanoma patient presenting with complete remission after treatment with clones of his own CD4+ T tumor killer cells has raised hopes that a method to control cancer is closer.
A 52-year old male metastatic melanoma patient was infused with billions of clones of his own CD4+ T tumor killer cells and had a complete remission. This is leading experts to believe that we are closer to being able to control cancer.
In the immunotherapeutic approach, Cassian Yee (Fred Hutchinson Cancer Research Center, WA, USA) cultured the 5 billion T cells outside of the patient’s body and programmed them to attack a specific type of melanoma cancer cell. The patient’s symptoms had vanished 2 years later.
The advantage of this method is that the patient suffers no toxic side effects as would happen with standard chemotherapy or radiation therapy. The research team admit that this is a breakthrough for scientists as many others have attempted to clone immune cells for such treatment but failed.
Some experts have deemed this treatment a breakthrough at demonstrating how the body’s immune system can be manipulated into treating cancer. Others are reacting with caution and advising that more research needs to be undertaken to confirm the results.
The patient was enrolled in a clinical research trial at the Fred Hutchinson Cancer Research Center following previous failures to respond to standard treatments. The patient’s melanoma was in an advanced metastatic state when the patient was infused with his own immune cells and it had spread to the lymph node in his groin and one of his lungs.
The patient’s symptoms had vanished within 60 days of treatment and 2 years after treatment PET and CT scans showed that no tumors were present despite having received no additional therapies.
Yee and his colleagues were surprised and delighted with the result but advise that these findings ought to be confirmed in a larger study before this can be considered a valid effective treatment.
Source: Hunder NN, Wallen H, Cao J et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N. Engl. J. Med. 358(25), 2698–2703 (2008).