Can Gene Therapy Reverse Diabetic Neuropathy?

A pipette and petri dish in a lab.
A pipette and petri dish in a lab.
A plasmid containing two human hepatocyte growth factor isoforms may improve quality of life for patients with painful diabetic neuropathy.

Gene therapy in the form of a plasmid containing two human hepatocyte growth factor isoforms administered via intramuscular injection may alleviate symptoms and improve quality of life in patients with painful diabetic neuropathy.

In addition, the plasmid —VM202 — may be particularly beneficial in those patients not taking gabapentin or pregabalin, according to researchers at Northwestern University.

In a recently completed double-blind, placebo-controlled study, 84 patients were randomly assigned to receive injections of 8 mg or 16 mg of VM202 per leg (calf muscles and lower leg) or placebo, with doses administered on days 0 and 14.

At 3 months, patients in the low-dose group experienced a significant reduction in pain compared with the placebo group, the researchers found.1 

“I am very excited about it. This is an enormous problem, and it has a huge impact on people’s lives. [These patients] spend so much time in agony,” said study investigator Jack Kessler, MD, who is a professor in the department of neurology at Northwestern University Feinberg School of Medicine in Chicago. 

“The data are very, very strong. One issue that remains to be resolved is if we are modifying the disease, and at this time, the jury is still out. In our last study, we had some improvement in patients to feel light stimuli, but we need additional data to say we are altering the course of the disease. If our phase 3 study gives us the same results, then this treatment will be the best option for treating diabetic neuropathy.”

Study Results

The primary outcome for this current study was change in the mean pain score measured by a 7-day pain diary. The analysis also included quality of life and pain measures, and measurement of intraepidermal nerve fiber density, according to Kessler.

The study showed that patients receiving 8 mg of VM202 per leg improved the most in all efficacy measures, including a significant reduction at 3 months in the mean pain score. The reductions in pain continued but were not statistically significant at 6 and 9 months.

“We would probably inject patients four times a year. If it turns out that we are actually making the neuropathy better, then it is reason to think patients would graduate from this, but if it turns out we are just treating the symptoms and not the disease, then we would see injecting the patients four times a year,” Kessler said in an interview with Endocrinology Advisor

The mean age of the patients in this study was 60 years (approximately 75% men), and the mean duration of diabetes was 15 to 16 years.

The researchers found that 48% of the patients experienced at least a 50% reduction in pain in the treated group compared with 17% in the placebo group. The study also demonstrated significant improvements in the brief pain inventory and the questionnaire portion of the Michigan Neuropathy Screening Instrument.  

The researchers noted that the largest reductions in pain were found among patients not on pregabalin or gabapentin.

There were no significant adverse events attributable to VM202 and this treatment was deemed safe and well tolerated.

More to Learn

It is hoped that VM202, which contains a human hepatocyte growth factor gene, will increase the local production of hepatocyte growth factor to help regenerate nerves and grow new blood vessels and subsequently reduce the pain.

“We believe we are getting a two-for-one treatment. We are supplying nourishment to the nerves, but we are also helping to improve blood vessel function,” said Kessler. “The most remarkable thing is that we pushed the dose up and we had literally not one serious side effect in the entire trial, only [injection] site soreness.”

A large trial is now planned, and the researchers hope to enroll 475 patients at 20 sites across the United States starting in December.

Amanda Peltier, MD, who is an assistant professor of neurology at Vanderbilt University in Nashville, Tennessee, said these study findings are interesting, and this approach could represent a new way of treating diabetic neuropathy with fewer treatment-related adverse effects.

“There is a huge unmet need for diabetic neuropathy as the current medicines have side effects and do nothing to improve or retard the progression of the underlying neuropathy, only treat the pain. In addition, our understanding of diabetic neuropathy has improved for type 1 diabetes, but there has been little headway in improving neuropathy for patients with type 2 diabetes,” Peltier told Endocrinology Advisor.

Looking Ahead

According to M. Sue Kirkman, MD, who is a clinical professor of medicine and the medical director of the Diabetes Care Center Clinical Trials Unit at the University of North Carolina School of Medicine in Chapel Hill, this is a quality of life issue.

Although there are several medications that may help symptoms, they are not effective in all patients and may come with significant side effects, Kirkman said.

“This trial showed promising results, but was relatively small and short-term. Larger and longer-term trials will be important to see if the benefits pan out, and also to get a better feel for potential adverse events. Up to now, treatments for diabetic neuropathy have been purely palliative, with no interventions that seem capable of actually improving nerve function,” Kirkman told Endocrinology Advisor

“There are some hints from this study that this agent could actually improve nerve function. If that pans out in larger trials, it would be very exciting, since lack of feeling in the feet from advanced diabetic neuropathy is a risk factor for foot ulcers and amputations.”


  1. Kessler JA et al. Ann Clin Transl Neurol. 2015;2(5):465-478.