The first association that comes to mind with steroids is muscle building, be it legal or illegal. But French biotech company Mapreg, based in the suburbs of Paris, wants to use neurosteroids to beef up the brain.

The company is working on bringing a neurosteroid analogue to the clinic for spinal cord injury later this year, with additional programs planned in traumatic brain injury and stroke, as well as neurodegenerative diseases.

What makes a neurosteroid is location, location, location. Mapreg Chief Scientific Officer Paul Robel told BioWorld Today, neurosteroids are "steroids that are synthesized in the brain."

Regular steroids exert their effects by entering the nucleus and binding to receptors there. But Robel and his colleagues discovered in 2000 that one particular neurosteroid, pregnenolone, binds to the protein MAP2, which is associated with microtubules in the cytosol. There, MAP2 induces those microtubules to assemble, or polymerize.

Microtubule polymerization has a number of functions. In neurons, they form an intracellular highway of sorts. Proteins are transported along polymerized microtubules from the nucleus down the axon.

At least as long as the neuron is in good working order: "When neurons are injured, microtubules depolymerize," Robel explained. And the level microtubule-associated proteins decrease as those microtubules disappear, because when they are not bound to microtubules, they are destroyed by proteases.

Such neurons tend to lose their dendrites, the parts of neurons where they receive incoming signals, and are consequently less able to communicate. To resume function, an injured neuron "needs to reconstruct its microtubules," Robel explained. Indeed, some cancer drugs induce cell death by disrupting normal microtubule function.

Mapreg is working to bring a pregnenolone analogue into the clinic, with a target date of later this year, company President Denis Le Bouteiller told BioWorld Today.

That analogue, known as MAP4343, also has shown some promise in animal studies testing it for use in traumatic brain injury and stroke, as well as some neurodegenerative diseases.

The company also is testing MAP4343 for possible effects in Alzheimer's disease. So-called tangles in Alzheimer's disease consist of hyperphosphorylated MAP2 and tau, another protein that is associated with microtubules.

The decision to test the compound in spinal cord injury, for which Mapreg has received orphan designation from the European Union, was made for several reasons. For one thing, "there is no product at the present time for spinal cord injury," Le Bouteiller said.

Recovery of function from spinal cord injury also is fairly easy to assess in animals. Mapreg has shown an improvement of function in animals if they are treated with MAP4343, within 24 hours of spinal cord injury.

Robel stressed the importance of that relatively long window of opportunity. He also noted that the compound does not work by inducing axonal outgrowth. Instead, he said, "the effect of our compound is on plasticity."

Privately held Mapreg has three full-time employees as well as several consultants, and currently is working on a funding round.

To date, it has received €2 million (US$3.04 million) in private equity, as well as another €1.5 million in subsidies.