With a goal of developing new treatments for multiple sclerosis, Serono SA and Paratek Pharmaceuticals Inc. formed an agreement to discover, develop and commercialize oral tetracycline derivatives.

The deal could mean up to $38 million in milestone payments to Paratek for the first product developed and approved. That figure does not include additional money in the form of an initial cash payment, a loan convertible into Paratek stock, research funding and further milestone payments if additional drugs are developed for MS or other indications.

Boston-based Paratek also would receive undisclosed royalties on products that reach the market. More specific financial details were not disclosed.

As the companies kick off their collaboration, they will seek to identify novel tetracycline derivatives for clinical development from a library of non-antibiotic lead compounds that were discovered by Paratek chemists. Geneva-based Serono gains worldwide development and commercialization rights to the compounds.

There is no orally administered disease-modifying drug approved to treat MS.

"One could say relief is on the way," said Stuart Levy, Paratek's chief scientific officer, vice-chairman and co-founder. "Here's a way patients could get up in the morning and take a pill, as they would a vitamin, and maintain their disease in a state of quiescence."

While Paratek was founded to rejuvenate tetracyclines to be used as antibacterial agents, countering drug resistance, the company stumbled across reports of tetracyclines showing an anti-inflammatory benefit in animals. Those reports led to a study conducted by Luanne Metz at the University of Calgary, who demonstrated that relapsing-remitting MS patients treated with minocycline, which is part of the tetracycline family, experienced disease protection.

"What she showed in 10 patients was that, sure enough, the disease was rested and they didn't have the relapses that they were having beforehand," Levy said.

However, long-term treatment with minocycline or any other broad-spectrum antibiotic causes many patients to have tolerability problems due to the side effects.

Paratek solved that problem by creating non-antibiotic tetracycline derivatives.

"The difference is we've been able to peel away the antibacterial portions of the molecule and retain what makes it an effective agent against inflammation and possibly nerve destruction," Levy said.

Tetracycline has been on the market for more than 30 years as an antibacterial treatment, and it has been used off-label for rheumatoid arthritis. It has a favorable safety profile that is well-documented. Paratek was attracted to a partnership with Serono because of the company's expertise in the fields of neurology, immunology and inflammation.

MS, a chronic, inflammatory condition of the nervous system, affects about 2 million people worldwide.

"The options now are injections, and there are four different injections," Levy said. "They have their limitations, and I don't think that any one is completely effective, but they are the best to be offered."

Paratek presented preclinical data on non-antibiotic tetracycline derivatives at Neuroscience 2005, the Society for Neuroscience's 34th annual meeting in San Diego. The data showed promising activity of the tetracyclines in a preclinical animal model of MS. The compounds have efficacy comparable to minocycline. Data presented also showed that three non-antibacterial tetracycline compounds, with different structures, demonstrated activity in reducing limb paralysis in the preclinical experimental autoimmune encephalomyelitis model of MS.

"We believe this has a very, very good chance of being the first oral out there for MS," Levy said, "but we have lots of hurdles to go yet."

It is too soon to say when the first compound might reach the clinic, he said.

Paratek's lead programs focus on compounds that can circumvent or block bacterial resistance and drugs that prevent infection by interfering with multiple adaptional response mechanisms in bacteria. The privately held company founded in 1996 has discovered a new class of antibiotics called aminomethylcyclines. The lead clinical candidate, BAY 73-7388, is the first product from that class being developed in partnership with Leverkusen, Germany-based Bayer HealthCare AG to treat serious infections.