CONFERENCE COVERAGE SERIES
American Neurological Association: 2002 Annual Meeting
New York, New York
13 – 16 October 2002
American Neurological Association Annual Meeting: Biomarkers and Mitochondrial Therapy
Editor's note: Alzforum received several belated comments on some interesting studies presented at the American Neurological Association's annual meeting in New York City last fall. We thus present summaries of these studies by our reporter Hakon Heimer, along with comments by Gjumrakch Aliev, Mark A. Smith, and George Perry, as well as John Blass and Mark Mattson.
I. Heme Oxygenase-1 Suppressor Is Candidate in the AD Biomarker Sweepstakes
Hyman Schipper and his colleagues at McGill University in Montreal, Canada, presented new developments in their ongoing work to evaluate the relationship of heme oxygenase-1 (HO-1) to AD. This stress protein catalyzes the oxidative degradation of heme to biliverdin, and the Schipper lab had previously demonstrated that HO-1 levels are higher in AD hippocampal and temporal lobe neurons and astrocytes compared with normal elderly controls (Schipper et al., 1995). Conversely, HO-1 levels appear to be lower in sporadic AD plasma and CSF compared to controls, suggesting the existence of a circulating suppressor that might serve as a useful biomarker for AD in its early stages or in therapeutic trials.
In one study, led by Steven Kravitz, the researchers reported an HO-1 suppressor (HOS) at work in the plasma of early sporadic AD patients, subjects with mild cognitive impairment, but not normal elderly controls. In a second study, led by Daniel Berlin, the researchers find evidence that the activity of this suppressor might be mediated by a heat-labile, heparin-binding glycoprotein.
References:
Kravitz S, Mawal Y, Sahlas DJ, Liberman A, Chertkow HM, Bergman H, Schipper HM. Heme oxygenase suppressor activity in Alzheimer plasma. Ann Neurol. 2002;52(3S);S31. Abstract 47.
Berlin D, Mawal Y, Liberman A, Schipper HM. Partial characterization of a heme oxygenase-1 suppressor activity in Alzheimer plasma. Ann Neurol. 2002;52(3S):S30. Abstract 42.
Coenzyme Q10 Slows Parkinson's Decline in Preliminary Study
The biggest splash at the meeting, at least in terms of media attention, was made by the preliminary report by the Parkinson Study Group that a dietary supplement appears to slow the progression of Parkinson's disease. The results appeared simultaneously in the Archives of Neurology (Shults et al., 2002). If larger studies confirm these results, coenzyme Q10 (CoQ10, also called ubiquinone) would be the first therapy that slows the underlying disease process, rather than merely improving symptoms temporarily.
Study leader Clifford Shults, of the University of California, San Diego, emphasizes that the 80 subjects in the study were not sufficient to prove that the drug was effective. "It would be premature to recommend that patients with Parkinson's take high doses of coenzyme Q10," he said in a news release.
Previous work by the laboratories of Shults, Richard Haas of UCSD, and Flint Beal of Weill Medical College of Cornell University, had found that CoQ10 levels are reduced in the mitochondria of Parkinson's patients, leading to the hypothesis that supplemental CoQ10 could help protect the mitochondria.
Shults and his collaborators randomly assigned patients to regimens of CoQ10 at dosages of 300, 600, or 1200 mg/day, or to a placebo group. Patients were assessed one month after beginning the study and then every four months during the 16-month study. Both patients and study investigators were blinded.
By the eighth month, patients on the highest dose were scoring significantly better on the Unified Parkinson Disease Rating Scale (which assesses mental function and mood, activities of daily living, and motor skills) than patients in all other groups. By the time the study ended, patients in the high-dose group were scoring 44 percent better than the placebo group. The lower CoQ10 doses slowed the functional decline relative to placebo, but were less effective. There was no significant difference in side effects between the CoQ10 and placebo groups.
If the drug had merely been ameliorating symptoms while the disease continued unchecked to kill neurons, the researchers would have expected the initial, first-month check-up to reveal improvement in the CoQ10 groups. Since that was not the case, Shults hypothesizes that the drug might have slowed the underlying progression of the disease over the 16-month period of the study. He stressed, however, that the study was designed to assess function, not to examine whether groups treated with CoQ10 did, in fact, have less damage to substantia nigra neurons. He and his colleagues hope to look at such damage in a larger study with hundreds of patients, perhaps even testing a dose larger than 1,200 mg/day.—Hakon Heimer
References
Paper Citations
- Schipper HM, Cissé S, Stopa EG. Expression of heme oxygenase-1 in the senescent and Alzheimer-diseased brain. Ann Neurol. 1995 Jun;37(6):758-68. PubMed.
- Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL, Nutt J, Shoulson I, Carter J, Kompoliti K, Perlmutter JS, Reich S, Stern M, Watts RL, Kurlan R, Molho E, Harrison M, Lew M, . Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50. PubMed.
Further Reading
No Available Further Reading