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Published on: October 3, 2011
Treatment of AIDS-associated myelopathy with L-methionine: a placebo-controlled study
A Di Rocco1, P Werner, T Bottiglieri
1Department of Neurology, Albert Einstein College of Medicine-Beth Israel Medical Center, PACC, 10 Union Square East, 2R, New York, NY 10003, USA. adirocco@aecom.yu.edu
Background:
The histopathology of AIDS-associated myelopathy (AM) closely resembles that of myelopathies due to cobalamin or folate deficiency, with white matter vacuolization in the spinal cord. The pathogenesis of AM appears unrelated to direct HIV infection of the spinal cord. There is abnormal trans-methylation metabolism in AM, with decreased availability of the methyl group donor S-adenosyl-methionine (SAM). The authors hypothesized that treatment with l-methionine, the direct metabolic precursor of SAM, might improve AM.
Objective:
To determine the safety and efficacy of l-methionine treatment in AM.
Methods:
Fifty-six patients with clinical diagnosis of AM were randomized to a Phase II, double-blind, placebo-controlled study comparing the effect of l-methionine 6 g/day in two divided doses with that of placebo. Study duration was 12 weeks. All patients had somatosensory evoked potentials with prolonged central conduction time (CCT) at entry. Change in CCT was the primary endpoint of the study. Frequency of adverse events (AEs) was used to assess safety. Secondary endpoints were strength, spasticity, and urinary function. Biochemical measurements included serum methionine and homocysteine and CSF SAM.
Results:
There were no significant differences in AEs between the two groups. Serum homocysteine increased in l-methionine-treated patients from 7.2 (+/-5.2 SD) to 12.6 (+/-6.15 SD) micromol/L. The mean CCT at baseline was 25.9 milliseconds (+/-7.3 SD) for the treatment group and 24.1 milliseconds (+/-7.0 SD) for the placebo group. At completion, it was 3.0 milliseconds (+/-6.1 SD) for the treatment group and 23.6 milliseconds (+/-5.5 SD) for the placebo group (p = 0.17). In a subset of 15 patients with CSF studies, SAM levels increased in the l-methionine but not in the placebo group (p = 0.07). There was no significant effect of treatment on strength, spasticity, or urinary function.
Conclusions:
l-methionine was safe and well tolerated although in some patients induced an increase of serum homocysteine. There was a nonsignificant improvement in CCT in treated patients but no benefit in any of the clinical measures.
Insights
L-methionine supplementation was safe for patients with AIDS-associated myelopathy (AM). While it increased S-adenosyl-methionine (SAM) levels, it did not significantly improve clinical symptoms or central conduction time (CCT).
Area of Science:
- Neurology
- Infectious Diseases
- Biochemistry
Background:
- AIDS-associated myelopathy (AM) histopathology resembles nutritional deficiencies like cobalamin or folate deficiency, characterized by spinal cord white matter vacuolization.
- AM pathogenesis is not linked to direct HIV spinal cord infection but involves abnormal trans-methylation metabolism and reduced S-adenosyl-methionine (SAM) availability.
- L-methionine, a precursor to SAM, was investigated as a potential therapeutic agent for AM.
Purpose of the Study:
- To evaluate the safety and efficacy of l-methionine treatment in patients diagnosed with AIDS-associated myelopathy (AM).
Main Methods:
- A Phase II, double-blind, placebo-controlled study randomized 56 AM patients to receive either l-methionine (6 g/day) or placebo for 12 weeks.
- The primary endpoint was the change in somatosensory evoked potentials' central conduction time (CCT), with safety assessed by adverse events (AEs).
- Secondary endpoints included neurological function (strength, spasticity, urinary function), with biochemical markers like serum methionine, homocysteine, and CSF SAM levels measured.
Main Results:
- L-methionine treatment was safe and well-tolerated, with no significant difference in AEs compared to placebo.
- Serum homocysteine levels increased in the l-methionine group, while CSF SAM levels showed a trend of increase (p=0.07).
- No significant improvements were observed in CCT, strength, spasticity, or urinary function between the l-methionine and placebo groups.
Conclusions:
- L-methionine is a safe treatment option for AIDS-associated myelopathy (AM), though it can elevate serum homocysteine levels.
- The study found a non-significant trend towards improved CCT in treated patients but no demonstrable clinical benefits.
- Further research may be needed to explore alternative therapeutic strategies for AM.
