BioWorld International Correspondent

NeuroSearch A/S is moving its candidate CNS drug NS2330 into the first of two large-scale Phase II trials planned this year in patients with Parkinson's disease.

The compound initially will be tested in a placebo-controlled, multicenter study of 250 patients with advanced-stage disease in Europe. Later this year, Boehringer Ingelheim, of Ingelheim, Germany, which entered a US$80 million pact with NeuroSearch early last year for developing NS2330, will conduct a second Phase II clinical trial, in patients with early stage Parkinson's.

The same compound, which appears to have several pharmacological effects, is already the subject of a Phase IIb trial in the U.S. and Canada involving 400 patients with Alzheimer's disease. Preclinical data indicate that NS2330 influences the levels of three important neurotransmitters - noradrenaline, acetylcholine and dopamine. Levels of the latter are severely depressed in Parkinson's patients, because of the widespread destruction of dopaminergic neurons in the substantia nigra region of the mid-brain.

The current standard treatment for Parkinson's comprises the administration of levodopa (L-dopa), a precursor of dopamine that can cross the blood-brain barrier, in combination with dopamine agonists. L-dopa is, initially, quite effective at alleviating Parkinson's symptoms, but only at very high doses as it is rapidly metabolized to dopamine before it can cross the blood-brain barrier. Over time, however, it gives rise to involuntary motor disturbances or diskynesias, because of an overloading of the remaining dopaminergic neurons. Dopamine agonist therapy does not give rise to the same problem, but is less effective at controlling the symptoms of the disease.

NS2330 takes a different tack. It blocks the reuptake of available dopamine and, according to NeuroSearch president and CEO J rgen Buus Lassen, also appears to have a neuroprotective effect. It shows the same efficacy as L-dopa in animal models of Parkinson's but without the accompanying diskynesia. Moreover, it is active at very low doses - about 0.25 mg to 0.5 mg per day - and the effect is long-lasting.

"If we could both treat the patients as effectively as with L-dopa and prevent the side effects from developing, we would really improve the quality of life for those patients," Buus Lassen told BioWorld International.