Acetyl-L-carnitine study on neuropathy

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Subject: Acetyl-L-Carnitine Reverses NRTI-Related Nerve Degeneration

Aug 09 - Acetyl-L-carnitine is a safe, well-tolerated agent that reverses nerve damage caused by nucleoside reverse transcriptase inhibitors (NRTI) treatment of HIV, British investigators report.

Acetyl-L-carnitine (ALCAR) relieves pain in patients with distal symmetrical polyneuropathy due to antiretroviral therapy, Dr. Mike Youle and his associates note in their report, published in the July 23rd issue of AIDS. However, it was unclear if the agent has an effect on neuronal regeneration.

Therefore, Dr. Youle, at Royal Free and University College Medical School in London, and his team treated 21 HIV-positive patients with antiretroviral neuropathy with oral ALCAR 1500 mg b.I.d. To quantify cutaneous innervation, the group performed indirect immunohistochemistry on skin biopsies from the leg excised at baseline and at 6 to 12 month intervals and compared the findings with biopsies obtained from five HIV-negative control subjects. At baseline, the authors observed an almost complete absence of fibers within the epidermis, dermis and the sweat glands in the patients.

Immunohistochemical staining of the biopsies revealed significant increases in innervation of epidermis, dermis and sweat glands after 6 months of ALCAR treatment, which remained elevated through 24 months of treatment, the researchers report. Most affected was mean immunostaining area for small sensory fibers. Clinical grade of neuropathic pain improved in 15 patients, remained at the same level in five and worsened in one. There were no side effects, adverse events or wound complications, the authors report, nor did ALCAR affect viral load or white cell counts. The authors suggest several mechanisms of action, including reduction of mitochondrial DNA damage by a direct antioxidant effect. The agent may also improve neuronal metabolic capacity, they suggest, by promoting glucose utilization and high-energy substrate oxidative metabolism.

"Peripheral neuropathy has been the principle complication limiting the use (of NRTIs)," Dr. Youle and his associates conclude, "and ALCAR may now offer an effective, pathogenesis-based management approach, allowing patients to remain on NRTI therapy."

AIDS 2004;18:1549-1560.

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Hart, M a,d,*; , DH a,*; Montovani, Cristina d; , Colette b; , Margaret c; Terenghi, Giorgio d; Youle, Mike c.

Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS. 18(11):1549-1560, July 23, 2004.

Abstract: 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.