ADX71441 is an experimental therapy with the potential to slow the progression of nerve damage in people who have Charcot-Marie-Tooth disease, or CMT.

Addex Therapeutics is developing the treatment in collaboration with the Charcot-Marie-Tooth Association.

How ADX71441 works

Some people with CMT have an extra copy of a gene that codes for peripheral myelin protein 22, or PMP22. PMP22 is necessary for the production of myelin, an insulating layer around nerve cells that promotes the transmission of nerve signals. Too much PMP22 gums up the works, however, ultimately causing the nerve damage associated with CMT.

One strategy for slowing the damage is decreasing the amount of PMP22 in nerve cells. Gamma-aminobutyric acid, or GABA, inhibits nerve signal transmission. It does this by reducing the activity of nerve cells when it binds to its GABA receptor.

Scientists think that the activation of GABA-B receptors reduces the PMP22 gene’s production of myelin protein. ADX71441 is designed to modify the activity of GABA-B receptors to reduce the protein’s  production.

A number of traditional drugs, such as baclofen, bind directly to the GABA receptor. They are effective but more likely to cause side effects. ADX71441, which scientists call a positive allosteric molecule, does not bind directly to the GABA receptor. Instead it binds to a secondary site, acting to modify GABA’s response.

ADX71441 in preclinical studies

On Jan. 7, 2013, Addex Therapeutics announced positive results from a study of ADX7141 in a rat model of CMT. The rats were producing too much PMP22 protein and showed symptoms of nerve damage, such as reduced grip strength.

At the end of a nine-week course of oral ADX71441, they were producing less PMP22. The result was muscle improvement and no additional loss of grip strength. Encouraged by the results, Addex affirmed its commitment to advancing ADX71441’s development.

Later that year, Addex reported results from a study that compared ADX71441 and baclofen’s effectiveness in a rat model of CMT. The animals received one of the two treatments for five days.

ADX71441 reduced PMP22 production — and the higher the dose, the larger the decrease, researchers said. The effects that ADX71441 and baclofen generated were similar, researchers said.

A study published in Neuropharmacology showed that oral ADX71441 was able to modulate the GABA-B receptor. The result was reduced pain, anxiety, and muscle spasticity in rodents.

Additional information

On Oct. 21, 2014, Addex announced that it would collaborate with the Charcot-Marie-Tooth Association to evaluate ADX71441 as a potential treatment for CMT. The association wants to work with drug makers on new therapies because not only is there no cure for CMT but there is no treatment to slow its progression. Research into other novel therapies is ongoing.

Note: Charcot-Marie-Tooth News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.