Researchers at the University of Warwick have suggested that eating broccoli could undo the damage caused to heart blood vessels by diabetes. They found that sulforaphane, a compound found in broccoli, can prevent biochemical dysfunction induced by hyperglycemia in cultured endothelial cells. People with diabetes have a particularly high risk of heart disease and stroke, which are linked to damaged blood vessels.
Sulforaphane may also trigger production of thioredoxin, which protects against cell damage in the heart.
Studies have also linked consumption of cruciferous vegetables, such as broccoli, with decreased incidence of ischemic stroke.
It has also been reported that 3,3′-diindolylmethane and indole-3-carbinol, other compounds found in cruciferous vegetables, may have anticancer, antiviral, antibacterial and antioxidant properties.
Rheumatoid Arthritis (RA) is a painful, chronic, progressive and disabling auto-immune disease. Newly released data has shown that a novel biologic, Actemra™ (tocilizumab), is superior to current standard of care in RA patients. Actemra™ is a humanised monoclonal antibody to the interleukin-6 receptor that blocks the activity of interleukin-6, a protein that plays a major role in the RA inflammatory process. Actemra™ is awaiting approval in the United States and Europe. In Japan, Actemra™ was approved for the treatment of RA in April 2008.
Other biologics are already used to treat RA and act at different points in the inflammatory process.
Orencia® (abatacept) works by reducing the activation of T-cells, which reduces the activation of other cells in the RA inflammatory process. Humera®(adalimumab), Enbrel®( etanercept) and Remicade® (infliximab) block the action of TNF-alpha, an inflammatory cytokine that leads to tissue damage. Mabthera® (rituximab) targets B cells, one of the key players in the pathogenesis of RA. Kineret® (anakinra) blocks the actions of the cytokine, IL-1.
The biologic medicines are usually prescribed together with the disease-modifying anti-rheumatic drug, methotrexate.
Quark Pharmaceuticals has recently announced that its partner Pfizer has begun a phase II clinical trial of a chemically modified small interfering RNA (siRNA) molecule in patients with diabetic macular oedema. PF-4523655 inhibits abnormal blood vessel growth and leakage independently of the VEGF pathway, reduces inflammation and suppresses apoptosis. Results from a Phase I/II trial completed by Quark on Pfizer’s behalf showed that PF-4523655 was safe and well tolerated in patients with wet age-related macular degeneration who failed to respond to currently approved therapies. The new trial will test the safety and efficacy of PF-4523655 compared with laser surgery.
siRNA molecules interfere with the expression of specific genes and there is currently much interest in using the technology to treat a wide range of diseases, although there are several challenges that must be overcome if exogenous siRNA is to become widely used.
Despite the challenges, several siRNA molecules have entered clinical trials including TD101 for pachyonychia congenita (PC Project / TransDerm), Sirna-027/AGN-745 for age-related macular degeneration (Allergan), metastatic melanoma (Duke University), CALAA-01 for solid tumours (Calando Pharmaceuticals), Cand5 for diabetic macular oedema (Opko Health) and I5NP for acute kidney injury following cardiac bypass surgery (Quark Pharmaceuticals).
A recent report in the journal Cell Metabolism (Cell Metab. 2008,7(5):377-388) identifies the serine/threonine kinase, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2), as a key component of the ghrelin signalling pathway. Ghrelin, which is produced in the stomach, is a polypeptide that promotes food intake by increasing production of the appetite-stimulating neurotransmitter, neuropeptide Y, by the hypothalamus. The authors established the role of CAMKK2 in appetite control and glucose tolerance both by experiments with CAMKK2-null mice and by administering the CAMKK2 inhibitor, STO-609, to normal mice. CAMKK2 is expressed at low levels in peripheral tissue and the effects of inhibition are likely to be brain-specific. The results suggest that blocking CAMKK2 has the potential to promote weight loss and improve glucose tolerance.
Other approaches to the management of obesity targeting the ghrelin pathway are being investigated. A group at the Scripps Institute has developed an anti-obesity vaccine that is directed against ghrelin and a number of groups are investigating small molecule modulators of the ghrelin receptor.
This week’s news has brought several stories that offer hope to Alzheimer’s patients and their carers. An experimental drug, Rember™, being developed by TauRx Therapeutics has been shown to slow progression of the disease. Rember™ is a new formulation of an old drug, methylene blue. The drug reduces the abnormal tangles of tau protein that are found in Alzheimer’s patients and thought to contribute to the disease. These tangles destroy neurons and their presence is strongly correlated with dementia. The company hopes to carry out further trials and, if these are successful, Rember™ could become available to patients in 2012.
Other researchers have also reported encouraging results for an experimental drug that targets tau tangles. AL-108 (Allon Therapeutics) is derived from an eight amino acid peptide (NAPVSIPQ: “NAP”) synthesized from a naturally occurring neuroprotective brain protein known as activity dependent neuroprotective protein (ADNP). The drug was tested in people with mild cognitive impairment and improved specific memory functions that are relevant in Alzheimer’s Disease.
In separate reports, angiotensin receptor antagonists and statins have both been linked with improved symptoms in Alzheimer’s patients.
Research suggests that people taking angiotensin receptor antagonists to treat hypertension are up to 45% less likely to develop Alzheimer’s Disease or dementia. The research was carried out by scientists at the Boston University School of Medicine and presented at the 2008 International Conference on Alzheimer’s Disease in Chicago. People taking the cholesterol lowering drugs known as statins for 5-7 years were also found to be at reduced risk of developing dementia according to a study published in the July issue of Neurology. (Neurology, Jul 2008; 71: 344 – 350)
Prostate cancer is the most common cancer among men, and it has been estimated that up to 10,000 men in the UK are diagnosed each year with the most aggressive form of the disease. A small scale clinical trial has now shown that abiraterone is able to shrink prostate cancer tumours in patients who have not responded to alternative medical or surgical treatments. Abiraterone works by inhibiting production of male hormones, which can stimulate the growth of prostate cancer cells, throughout the body and not just in the testes.
Many of men on the trial reported significant improvements in their quality of life and some were able to stop taking morphine for control of pain caused by the cancer spreading into their bones.
A study published in the July 18th issue of The Lancet shows that a drug once used in Russia to treat hayfever has the potential to improve symptoms in dementia patients. The study of 183 patients, tested dimebon (dimebolin) vs placebo in patients with untreated mild-to-moderate dementia. Patients taking dimebon improved over a six month period whilst those taking placebo got worse.
A smaller group of patients who continued taking dimebon for a further six months showed continuing improvement over this period. This ongoing improvement is seen as particularly important since none of the approved drugs for Alzheimer’s Disease has shown increasing improvement over twelve months. Although this was a relatively small study, the initial results are very encouraging and warrant further investigation.
In a separate study, also reported in The Lancet, immunisation against the amyloid-beta peptide was shown to clear amyloid plaques from the brain, but not to prevent the progressive neurodegeneration associated with Alzheimer’s disease.