Brain energy boost slows Alzheimer's
glucose is helping to roll back the symptoms of Alzheimer's
A Colorado biotech company called Accera has developed Ketasyn (AC-1202), an orally given liquid that is converted by the liver into ketone bodies. The brain can use these molecules as a source of energy - even when it can't process glucose. At this week's Annual International Conference on Prevention of Dementia, run by the US Alzheimer's Association, Accera took the opportunity to disclose some data from a Phase IIb trial of Ketasyn. Of the 152 patients enrolled, the patients receiving the drug - in combination with other Alzheimer's medication, showed significant improvement in memory and cognition (using the AD Assessment Scale-Cognitive score or ADAS-Cog). The latest figures estimate that 26.6 million people are living with Alzheimer's disease globally. Scientists from the John Hopkins University predict that those numbers will quadruple by 2050 to more than 100 million, at which time 1 in 85 persons worldwide will be living with the disease. Given that current treatments concentrate on the symptoms of the disease rather than the underlying causes, new drugs are needed if these numbers are to be reduced. According to Accera, the main fuel for the brain is the sugar glucose; it is used both to generate energy and to produce chemicals such as cholesterol and acetylcholine. Neuronal cells do not efficiently utilize fats, and low glucose levels cause disturbances in cholesterol levels, cholinergic defects, and altered processing and clearing of cellular proteins - all of which are physiological hallmarks of Alzheimer's. For example, disturbances in cholesterol metabolism are known to affect the processing of the Amyloid Precursor Protein (APP). The potentially protective effect of Ketasyn on brain cells is, therefore, a new way of treating Alzheimer's. The results were even better (5 points ADAS-Cog compared to 3.5 point improvement) in a subgroup of patients who didn't have a genetic predisposition to the disease - characterised by the presence of the epsilon4 allele of the apolipoprotein E (ApoE). Those patients who didn't have this allele showed improved memory and cognition, while AC-Ketasyn appeared to stabilise the disease in those with ApoE4. "The significant and rapid cognitive improvements observed in ApoE4 negative patients support the efficacy observed in our Phase IIa study," said Dr Lauren Costantini, Accera's vice president of clinical development. "It also provides further evidence of the link between Alzheimer's disease and neuronal hypometabolism," she added, referring to AC-1202's novel mechanism of action. Several other promising Alzheimer's treatments were outlined at the conference. Neurochem outlined phase III data for Alzhemed (tramiprosate), an amyloid-beta inhibitor. By binding to the soluble form of this protein, it is thought to interfere with amyloid plaque formation. However, the company discovered there were significant and unexpected differences in the data between the study's many sites, making it very difficult to determine the total outcome of the trial. Therefore, it is working to account for the site differences, so it can analyze the data to determine the total results. "At this time, we don't have the results for the Alzhemed Phase III clinical trial," said Dr Sam Gandy, head of the Alzheimer's Association's Medical & Scientific Advisory Council. "However, we have learned important lessons about how to do these types of very complex, long-term, large-scale Alzheimer's trials, which in itself is very important because there are now so many promising Alzheimer's therapies in the pipeline." Biopharamceutical company Medivation, presented data of Dimebon - a small molecule that has been shown to inhibit brain cell death in preclinical models relevant to Alzheimer's disease and Huntington's disease. Over the course of year-long Phase II trial, the drug was beneficial according to five clinical tests. One of them was ADAS-Cog, with patients showing a 6.9 point improvement over placebo. Eli Lilly were also present, showing results of a Phase II trial of LY450139, a gamma-secretase inhibitor - the protein that slices up amyloid precursor protein (APP) to form the smaller amyloid- beta peptide.