Peripheral Neuropathy Can Lead To Mitochondrial Dysfunction, Acidosis: Study

New research suggests that debilitating nerve damage known as peripheral neuropathy may be linked to mitochondrial problems, resulting in low bioenergy levels, acidosis, and other health problems. 

Canadian researchers published a study last month in the medical journal Molecular Pain, which indicates that peripheral neuropathy, particularly that caused by traumatic nerve injury, is associated to mitochondrial dysfunction. Other studies have reportedly linked other forms of neuropathy, or nerve damage, to problems with mitochondria as well.

Some drugs have also been known to cause mitochondrial toxicity, which results in a variety of problems, including peripheral neuropathy, pancreatitis, Parkinson’s disease and other disorders.

Mitochondria are membranes found in cells that create the chemical energy those cells need to function. Mitochondrial toxicity, most often associated with antiretroviral drugs used to treat HIV, damages or reduces the amount of mitochondria in the body’s cells.

Researchers developed a way to examine the bioenergetic needs of nerves in mice, meaning how much bioenergy the nerves needed to function. They found that when nerves were injured, they needed more bioenergy, which is provided by mitochondria. The increased bioenergy requirements taxed the mitochondria, leading to increased oxideation of glucose and sugar and causing increased oxygen consumption.

The study found that this could lead to a decline in the body’s energy production and conditions of acidosis, which means that blood acid levels raise to potentially dangerous levels.

Peripheral Neuropathy Linked To Antibiotics

The study comes amid increasing concern over long-term peripheral neuropathy linked to antibiotics that are part of a class of medications known as fluoroquinolones, which include Levaquin, Avelox, and Cipro.

In 2013, the FDA issued a drug safety communication to announce that it is requiring the manufacturers of Levaquin and other fluoroquinolones to change their warning labels about the risk of the nerve problems, providing warnings for the first time that symptoms may continue for months or even years after an individual stops taking the drug.

While prior warnings suggested that it was rare of users to suffer a Levaquin neuropathy injury and that the problems often resolve once the medication is no longer used, fluoroquinolone antibioitics have actually been linked to a large number of reports involving permanent and disabling nerve damage that may last the rest of a user’s life.

In 2014, a study published in the medical journal Neurology added further support for these warnings, indicating that side effects of Levaquin and other fluoroquinolones may double the risk of peripheral neuropathy.

In the summer of 2014, the Southern Network on Adverse Reactions (SONAR), based at the University of South Carolina, filed a citizen’s petition with the FDA to force the agency to add a mitochondrial toxicity black box warning to Levaquin, Avelox, Cipro and other related antibiotics.

According to the petition, research by the FDA and others have linked all fluoroquinolone antibiotics to a risk of mitochondrial damage. However, SONAR found that FDA’s adverse event database recorded a significantly higher number of complaints from doctors and patients involving problems with Levaquin than with other drugs of the same class.

SONAR notes in its petition that mitochondrial toxicity manifests in a number of ways, and has likely been reported to the FDA as other potential Levaquin side effects, such as liver damage.

The group estimated that mitochondrial toxicity could be the cause of as many as 31% of the nearly 80,000 Levaquin adverse events reported between November 1, 1997 and February 3, 2011. The group also noted that only between 1% and 10% of adverse events are estimated to actually be reported, suggesting the true extent of the problems may be substantially greater.

Stronger warnings about the risk of mitochondrial toxicity from Levaquin could lead doctors to consider using alternative antibiotics, according to the group. This could prevent consumers from suffering serious and potentially life-long complications, as well as reduce costs on the health care industry, Medicare and Medicaid.

A growing number of Levaquin lawsuits, Avelox lawsuits and Cipro lawsuits are now being pursued on behalf of users diagnosed with peripheral neuropathy after using the antibiotics, alleging that the manufacturers failed knew or should have known about the risk, yet failed to adequately warn consumers and the medical community.

In August, the U.S. Judicial Panel on Multidistrict Litigation (JPML) centralized all of the fluoroquinolone lawsuits pending throughout the federal court system before U.S. District Judge John R. Tunheim in the U.S. District Court for the District of Minnesota. Given the similar questions of fact and law, the cases have been consolidated for pretrial proceedings to reduce the risk of duplicative discovery into common issues, avoid conflicting pretrial orders from different courts and to serve the convenience of the parties, witnesses and the courts.