More Older Drugs Show Promise in Alzheimer’s Trials

We recently reported that a Russian antihistamine, Dimebon, did well in a clinical trial in Alzheimer patients. In the last few weeks reports have come from the International Conference on Alzheimer’s Disease of several new treatments that have been claimed to have positive effects in small clinical studies. They include the following:

1. Methylene blue used to be used for urinary infections. Formulated as methylthionimum chloride, or Rember®, it was given for 2 years to 320 patients with mild to moderate Alzheimer’s. The treatment effect was stated to be twice that of donepezil (Aricept®), according to the chief investigator, who happens to be founder and director of TauRx Therapeutics. Rember attacks the tangles seen in Alzheimer brains, while most other new agents tackle the amyloid plaques which are also seen.
2. PBT2 is a metal-protein-attenuating compound, related to clioquinol, an antifungal drug that is toxic to nerve tissue at high doses. PBT2 given for 12 weeks caused a reduction in the level of amyloid-beta in the spinal fluid, but not in the plasma, and resulted in some improvement in two tests of function – trail-making drawing and verbal fluency. The presenter of this study is a consultant and stockholder with Prana Biotechnology, the ‘parent’ of PBT2.
3. AL-108 is a small peptide agent that’s believed to reverse the degeneration of microtubules in nerve cells which leads to the formation of tangles in Alzheimer’s disease. In a study of 144 patients with mild cognitive impairment - a precursor to Alzheimer’s – Al-108 was given nasally for 12 weeks. There was a significant, persistent, dose-dependent improvement in two tests measuring short-term recall and working memory. The manufacturers of AL-108 are Allon Therapeutics Inc. The study was presented by the discoverer of the drug, who’s the Chief Scientific Officer for Allon.
4. Intravenous immunoglobulin (IVIG) is an infusion of a pool of antibodies extracted from the plasma of more than 1000 blood donors. It can help patients with immune deficiencies, autoimmune diseases, and inflammatory diseases. A study in 24 mild-to-moderate Alzheimer’s disease patients showed no differences between the IVIG and placebo at 6 months, but at 9 months the 16 Alzheimer patients performed significantly better on two major scales than the 8 placebo patients. IVIG is expensive (about $2,500 every 2 weeks), and is likely to be more useful as a tool towards developing new approaches to treatment than a treatment per se.
5. Analysis of a US Veterans Affairs database has allowed researchers to examine possible befits of one type of high blood pressure medication – the angiotensin receptor blockers, or ARBs – on the occurrence and progression of dementia. They found that patients taking ARBs had about a 35% to 40% lower chance of getting Alzheimer’s or dementia. And in those already suffering from Alzheimer’s or dementia, ARB-takers had a 45% lower chance of developing delirium, nursing home admission, or death. The study didn’t report specifically if angiotensin converting enzyme [ACE] inhibitors, which are closely related to ARBs, had a similar protective effect. But there have been previous reports that those ACE-inhibitors that cross into the brain can delay the onset of dementia.

This particular collection of new uses for old drugs brings the likelihood that we shall have effective medication for Alzheimer’s sooner rather than later.