Boston Children’s Hospital Develops a Skin Cream for Peripheral Neuropathy

Researchers at Boston Children’s Hospital developed a skin cream that may relieve a difficult-to-treat form of peripheral neuropathy called small-fiber neuropathy, which causes pain, tingling, and a loss of sensation, usually starting in the feet. The common ailment affects millions of people with diabetes. The findings were reported in a January edition of the Proceedings of the National Academy of Sciences. The topical cream has only been tested on mice so far, but researchers say that the results look promising.

The loss of sensation in the feet can increase the chances of ulcers and infections that may lead to amputation, a well-known problem associated with diabetes. Small-fiber neuropathy also can result from other autoimmune diseases, HIV infection, and chemotherapy treatment. The current treatment options available only consist of painkillers to reduce pain, but according to Boston Children’s Hospital officials, these medications do not restore sensation and do not address the underlying cause of the neuropathy.

“People have been able to treat pain in small-fiber neuropathy, but the treatments cause side effects, and there’s nothing that can help the loss of sensation, which can contribute to people losing limbs,” says Gabriel Corfas, of the F.M. Kirby Neurobiology Center at Boston Children’s.

Corfas began to think of a new treatment option because small-fiber neuropathy is known to degenerate the nerve endings of sensory neurons and the loss of a group of factors that stimulate nerve growth known as GNDF. So he wondered if replenishing GDNF could improve sensory neurons’ health and function. “Other investigators have been testing the potential use of GDNF in neuropathy, but since GDNF is a large molecule, the only way to get it into the nervous system is through invasive methods such as injections into the spinal cord,” Corfas says.

Corfas and colleagues created a skin cream containing a small-molecule compound, called XIB4035, that is known to enhance GDNF’s effects, rather than using GDNF itself. “When you use an enhancer, you need less GDNF to activate receptors on the sensory neuron,” Corfas explains. “The receptors are activated for longer, and GDNF’s effects are stronger.”

According to a report from Boston Children’s:

When mice with small-fiber neuropathy were given the skin cream, they showed improvements in nerve structure and regained sensitivity to heat in their paws as compared with controls receiving an inactive cream. Sensation improved in both diabetic mice and mice that developed small-fiber neuropathy through genetic manipulation. Even mice with advanced disease showed improvements.

Corfas says that the study offers hope for a more targeted, practical treatment for small-fiber neuropathy. “By giving an enhancer, you help only the cells that naturally are exposed to the growth factors and that have the receptors for them,” he says. “Also, because the enhancer is given topically, we are effectively putting it into the neurons, which have their endings in the skin. So there is very little systemic exposure, and we believe there will be far fewer side effects.”

The team is now examining whether the cream has any value for large-fiber neuropathy, which involves motor fibers and is often caused by injury. They also will further explore skin absorption of XIB4035, as well as the effects of systemic delivery.