New Hope for Diabetics or Just Wishful Thinking

New Hope for Diabetics or Just Wishful Thinking

Marvin Ackerman, MD - Treatment for Diabetic Neuropathy

A few weeks ago, I received an email from a relative who had noticed an article touting the virtues of a specific form of vitamin B12 called methylcobalamine as a therapeutic agent for treating diabetic neuropathy.

I managed to locate the company mentioned in the article and ordered some for one of my patients. After about one month of treatment, my patient reports no change. We are still hopeful, but our optimism is running out of time. This was followed several days ago by an Associated Press report written by Randolph E. Schmid concerning research by a team led by Michael Brownlee of the Albert Einstein College of Medicine. It seems that a synthetic form of vitamin B1, or thiamin, which is used in Europe to treat nerve problems has been found to prevent retinal damage of the eye in rats. The product, known as benfotiamine, was given to rats for 36 weeks. These rats were free of the retinal damage observed in a group of untreated control rats. Brownlee hopes to try benfotiamine in humans, in whom diabetes is the leading cause of blindness, in the near future. The rationale as to how benfotiamine works is based on its ability to boost the activity of the enzyme transketolase, which blocks the cell damage created by an inability to regulate sugar, resulting in accumulation of byproducts. However, if you are thinking of going out and buying some vitamin B1 in the hope that it might also work, forget it. It doesn’t help at all.

At least forms of vitamin B are known to have a salutary effect on nerves, but how about hedgehog proteins? You read that right. However, forget it, hedgehog proteins do not come from hedgehogs, they merely look like them. This all came about because a great deal of gene research is done on the fruit fly known as Drosophila. When scientists first discovered the protein they thought that it looked like a curled up hedgehog hence the name. Later they found that in mammals there are actually three types of these genes. They named them after the desert hedgehog, the Indian hedgehog, and the sonic hedgehog. Apparently, each one plays an extremely important role in the developing mammalian embryo where they regulate segmental polarity. The sonic form is associated with the development and patterning of the central nervous system. During development, it is secreted by the notochord leading to dorsal plate formation and thus establishment of the anterior-posterior axis, and indirectly the distal-proximal axis. In other words, it makes sure that your spinal cord runs up and down, your fingers point away from your shoulder, and your thumb is on top rather than on the bottom. It also specifies that you have two eyes. Without this gene, our limbs would be extremely short and we would be deficient intellectually. The desert form works instead on the peripheral nervous system where it appears to “focus specifically on cellular elements of the epi- and perineural sheaths.”

Calcutt et al from the University of California at San Diego published an article called “Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy” in the February 2003 issue of the Journal of Clinical Investigation in which they claimed to find that diabetes causes a significant decrease in desert hedgehog mRNA in the peripheral nerve of maturing diabetic rats. They then tried treating these animals with a sonic hedgehog-IgG fusion protein. The results were quite impressive. There was full restoration of motor- and sensory-nerve conduction velocities. There was also maintenance of the axonal caliber of large myelinated nerve fibers. Other deficits caused by diabetes were also rectified or ameliorated including retrograde transport of nerve growth factor and sciatic-nerve levels of calcitonin gene-related product and neuropeptide Y, and loss of sensation to heat in the paw.

This is exciting stuff. Eva L. Feldman, writing in the same issue of JCI, called the Calcutt group’s work elegant. Her commentary, entitled “Oxidative stress and diabetic neuropathy: a new understanding of an old problem,” traces the major mechanisms involved in diabetic neuropathy. She adds her speculative opinion to that of the authors of the study by stating, similar to them, that combination therapy of this sort promises considerable therapeutic potential for the treatment of diabetic neuropathy.

Diabetes is becoming a scourge in the Western world where it can be considered to have reached epidemic proportions. Diabetic retinopathy is the most common cause of adult blindness in the United States. Diabetes is the leading cause of renal failure and more than half of patients develop neuropathy, which is the most common cause of nontraumatic amputations and autonomic failure. If research of this sort pans out, and can be translated into ways of treating diabetic neuropathy and retinopathy, two of the most feared aspects of the disease may be on their way to extinction.

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