Novel immunotherapeutic treatment for malignant glioma
Scientists at Cedars-Sinai Medical Center (LA, USA) have developed a novel treatment method for malignant glioma in mice. The study, published in the September issue of Cancer Research, combined dendritic cells (DCs) and viruses containing a newly identified cytokine to produce the highly effective antitumor treatment. This combined approach not only destroys cancerous cells, but also protects against tumor rechallenge.
A genetically engineered virus, which expresses high levels of interleukin (IL)-23 was attached to bone marrow-derived DCs and injected directly into intracranial tumors in mice. John Yu, Neurosurgeon, Codirector of the Comprehensive Brain Tumor Program at the Maxine Dunitz Neurosurgical Institute (LA, USA), and senior author of the Cancer Research article commented “IL-23 promotes the function of DCs and memory T cells, important components in providing an initial response and long-term immunity against tumor cells.” He added “DCs and IL-23 appear to work very well together against glioma cells. Intertumoral injections brought about robust infiltration of tumor-killing T cells and established a strong systemic response specific to the tumor cells.”
After intertumoral injection of the DC-IL-23, an impressive 80% of mice survived beyond the 120-day observation period, compared with only 20% of control mice. These mice also successfully fought off tumor rechallenge and remained tumor-free until the end of the study.
Keith Black, Director of the Maxine Dunitz Neurosurgical Institute and Interim Chair of the medical center’s Department of Neurology remarked “Most antitumor gene strategies attempt to deliver genes to tumor cells directly, but gliomas are especially challenging owing to their highly invasive and migratory characteristics.” He continued that “By combining the tumor-tracking properties of bone marrow-derived neural stem cells with IL-23, we are able to initiate a very powerful antitumor response that tracks to migrating glioma islands and offers long-term protection.”
According to the Brain Tumor Society, every year, approximately 200,000 people in the USA are diagnosed with primary or metastatic brain tumors. Gliomas make up approximately 40% of all brain tumors; the most common of these in adults being the glioblastoma. This aggressive brain tumor has very poor survival rates, with 30% survival 1 year after diagnosis and only 2% 10 years after.
The potential of the treatment described above is astounding. Thousands of lives could be saved, or at least considerably extended, if this method successfully passes clinical trials.
Traumatic brain injury: improvement of memory by rivastigmine
Rivastigmine, a drug usually associated with the treatment of Alzheimer’s disease, has been shown to also be effective in improving cognitive measures in patients with traumatic brain injury (TBI). The research, published in the September 12 issue of Neurology, showed a positive improvement in memory of a subgroup of TBI sufferers after treatment with the cholinesterase inhibitor.
Rivastigmine (3–6 mg/day) was administered to 157 patients over a 12-week period who had suffered a TBI at least 12 months prior to the study. After the 12-week period, mild-to-severe TBI sufferers who had taken rivastigmine showed a marked improvement in attention and verbal memory tasks. This improvement was significantly higher than those of control patients.
The study’s lead author, Jonathan M. Silver of the New York School of Medicine (NY, USA), commented “With an estimated 1.5 million people suffering from TBI each year in the USA, rivastigmine shows promising results for these patients with moderate-to-severe memory loss.” With regards to the positive effect of rivastigmine to memory only being significant in a subgroup of moderate-to-severe TBI sufferers, he added “The beneficial effect of rivastigmine may not become apparent unless there is significant depletion of cholinergic activity in relevant brain regions causing a more profound impairment in memory or attention. This is an area where more research will be required to confirm these findings and to better define who may have the best response with rivastigmine.”
The CDC reported that in the USA alone, 270,000 people experience moderate or severe TBI. Rivastigmine offers a hope of treatment for these and possibly other sufferers of TBIs, which may be determined as more research is carried out.
MRI shows developmental delay of gray matter in autism
It has often been hypothesized that autism spectrum disorder (ASD) is caused by rapid neural growth and maturation, resulting in damage to the brain. However, this theory has been challenged recently by Stephen Dager and colleagues, as reported in the August 22 issue of Neurology. The study used gradient echo (GE) magnetic resonance imaging (MRI) to demonstrate molecular signs of developmental delay in the gray matter of children with ASD.
The brains of 60 children, aged 2–4 years, who had been recently diagnosed with ASD, were imaged using GE MRI and compared with those of ten children with typical development (TD). The study compared the T2 transverse relaxation times of both gray and white matter in each group. These values, the authors say, are a method of determining the level of maturation of the brain; a short T2 time suggesting more advanced development, and a long T2 time indicating less maturity.
The children with ASD had a longer gray matter T2 time than those with TD (119 compared with 118 ms; p = 0.009). There was no significant difference in T2 times in white matter, suggesting that less maturation occurs in the gray matter of children suffering from ASD, but not the white matter.
Dr Dager, of the University of Washington (DC, USA), commented “Our findings suggest delayed growth, not accelerated growth.” In the article, the authors speculated “Our T2 gray matter findings in the children with ASD, studied soon after clinical diagnosis was established, may reflect brain mechanisms involving neuroinflammation, which have been implicated in this disorder.” They continued “Such processes are typically accompanied by edema and would result in increased T2 relaxation.”
The CDC reported that in the USA, up to 500,000 individuals between the ages of 0 and 21 years suffer from ASD. There is currently no cure for the disease and, although there are a wide variety of treatments currently available, it is clear that by better understanding of the disorder, treatment methods may be improved. The use of T2 time measurement to assist in the understanding of the biological mechanisms underlying ASD may aid in the identification of genes associated with it. This would then allow research into therapies that target the genes associated with ASD, hopefully providing more effective treatment.
A glass a day keeps Alzheimer’s away
Researchers at the Mount Sinai School of Medicine (NY, USA) have shown that a glass of Cabernet Sauvignon a day may reduce the risk of developing Alzheimer’s disease (AD). The study, which is currently in press and will be published in the November issue of The FASEB Journal, used a mouse model of AD to illustrate the positive effects of regular but moderate wine consumption.
AD has commonly been associated with the build up of plaques in the brain, caused by an increase in β-amyloid (Aβ) peptides. Mice with AD-type Aβ neuropathology were given the equivalent of one glass of Cabernet Sauvignon per day for approximately 7 months. The researchers found a significant reduction in AD-associated cognitive deterioration as well as decreased Aβ neuropathy.
Dr Giulio Maria Pasinetti and Dr Jun Wang at Mount Sinai School of Medicine stated “Our study is the first to report that moderate consumption of red wine in a form of Cabernet Sauvignon delivered in the drinking water for approximately 7 months significantly reduces AD-type Aβ neuropathy, and memory deterioration in approximately 11-month-old transgenic mice that model AD.” They continued “This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the US FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia.”
The Alzheimer’s Foundation of America reports that there are currently approximately 4.2–5.8 million AD sufferers in the USA. The risk of developing AD increases dramatically with age. With an aging population, the number of AD sufferers is expected to keep climbing as more people live longer. There is currently no cure for the disease. Research into the underlying cause of AD is essential in order to identify possible therapeutic targets.
The study authors commented “This new breakthrough is another step forward in Alzheimer’s research at Mount Sinai and across the globe for this growing health concern that has devastating effects.” They continued “These findings give researchers and millions of families a glimpse of light at the end of the long dark tunnel for future prevention of this disease.”
About the news in brief
If you have newsworthy information, please contact: Lucy Tipton, Assistant Commissioning Editor, Expert Review of Neurotherapeutics, Future Drugs Ltd, 2 Albert Place, Unitec House, Finchley Central, London N3 1QB, UK [email protected] Fax: +44 (0)20 8343 2313