Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy

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CNS Drugs. 2007;21 Suppl 1:25-30; discussion 45-6. Links

Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy.

Youle M.

Royal Free Centre for HIV Medicine, Royal Free Hospital, London, UK. mike@...

Nucleoside analogue reverse transcriptase inhibitors (NRTIs), used as part of highly active antiretroviral therapy for the treatment of HIV and AIDS, disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl-L-carnitine (ALC) enhances neurotrophic support of sensory neurons, potentially causing symptom relief and nerve regeneration, and in addition has numerous other effects on metabolic function that might be of benefit in such patients.ALC has been given to HIV patients with symptomatic ATN in a number of clinical studies administered either twice daily intramuscularly or as oral sachets or tablets. It has been shown to significantly reduce a variety of validated pain ratings, and is generally safe and well tolerated. Using a measure of neuronal innervation in standardised skin biopsies of the affected area, cutaneous nerve density has been improved by the administration of ALC in subjects with symptomatic ATN and reduced epidermal and dermal innervation, associated with clinical improvement, which was maintained over a 4-year period. Improvements were seen in both the structure and function of small sensory fibres, which were sustained over time whilst subjects received ALC. Other open-label, non-randomised studies have shown similar benefits in patients with ATN in terms of pain reduction over the short term.Further placebo-controlled studies of both treatment and prophylaxis have been completed and are under analysis to characterise further the usefulness of this pathogenesis-based therapy for ATN.

Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy.

AIDS. 2004; 18(11):1549-60 (ISSN: 0269-9370)

Hart AM ; AD ; Montovani C ; C ; M ; Terenghi G ; Youle MBlond McIndoe Centre, Royal Free and University College Medical School, London, UK.

BACKGROUND: Nucleoside analogue reverse transcriptase inhibitors (NRTI) disrupt neuronal mitochondrial DNA synthesis, impairing energy metabolism and resulting in a distal symmetrical polyneuropathy (DSP), an antiretroviral toxic neuropathy (ATN) that causes significant morbidity in HIV disease. Serum acetyl-l-carnitine (ALCAR) levels are decreased in neuropathy associated with NRTI therapy. ALCAR enhances neurotrophic support of sensory neurons and promotes energy metabolism, potentially causing nerve regeneration and symptom relief. OBJECTIVE: To assess the efficacy of oral ALCAR (1500 mg twice daily) for up to 33 months in an open cohort of 21 HIV-positive patients with established ATN. METHODS: Skin biopsies were excised from the leg before ALCAR treatment, at 6-12 month intervals thereafter and from HIV-negative non-neuropathic controls. Fibre types in epidermal, dermal and sweat gland innervation were quantified immunohistochemically. RESULTS: After 6 month's treatment, mean immunostaining area for small sensory fibres increased (epidermis 100%, P = 0.006; dermis 133%, P < 0.05) by more than that for all fibre types (epidermis 16%, P = 0.04; dermis 49%, P < 0.05; sweat glands 60%, P < 0.001) or for sympathetic fibres (sweat glands 41%, P < 0.0003). Compared with controls, epidermal, dermal and sweat gland innervation reached 92%, 80% and 69%, respectively, after 6 month's treatment. Innervation improvements continued (epidermis and dermis) or stabilized (sweat glands) after 24 month's treatment. Neuropathic grade improved in 76% of patients and remained unchanged in 19%. HIV RNA load, CD4 and CD8 cell counts did not alter significantly throughout the study. CONCLUSIONS: ALCAR treatment improves symptoms, causes peripheral nerve regeneration and is proposed as a pathogenesis-based treatment for DSP.

PreMedline Identifier: 15238773

MORE ON THE STUDY, COURTESY OF JULES LEVIN

http://www.natap.org/2000/salvage/salv_rpt04.htm

THIS IS AN ONGOING STUDY THAT IS NOT CURRENTLY RECRUITING ANYMORE

http://clinicaltrials.gov/show/NCT00050271

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