Re: Coenzyme Q10 and CMT - 2003 research

[Guest guest]

J Investig Med. 2003 Sep;51(5):261-83.

Molecular mechanisms, diagnosis, and rational approaches to management of and

therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies.

Saifi GM, Szigeti K, Snipes GJ, CA, Lupski JR.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston,

TX, USA.

Erratum in:

J Investig Med. 2004 Jan;52(1):50.

During the last decade, 18 genes and 11 additional loci harboring candidate

genes have been associated with Charcot-Marie-Tooth disease (CMT) and related

peripheral neuropathies. Ten of these 18 genes have been identified in the last

2 years. This phenomenal pace of CMT gene discovery has fomented an

unprecedented explosion of information regarding peripheral nerve biology and

its pathologic manifestations in CMT.

This review integrates molecular genetics with the clinical phenotypes and

provides a flowchart for molecular-based diagnostics. In addition, we discuss

rational approaches to molecular therapeutics, including novel biologic

molecules (eg, small interfering ribonucleic acid [siRNA], antisense RNA, and

ribozymes) that potentially could be used as drugs in the future.

These may be applicable in attempts to normalize gene expression in cases of CMT

type 1A, wherein a 1.5 Mb genomic duplication causes an increase in gene dosage

that is associated with the majority of CMT cases. Aggresome formation by the

PMP22 gene product, the disease-associated gene in the duplication cases, could

thus be avoided. We also discuss alternative therapeutics, in light of other

neurodegenerative disorders, to disrupt such aggresomes.

Finally, we review rational therapeutic approaches, including the use of

antioxidants such as vitamin E, coenzyme Q10, or lipoic acid to relax potential

oxidative stress in peripheral nerves, for CMT management.