12:00 AM
Mar 31, 2008
 |  BioCentury  |  Product Development

Reclamation in ALS

Knopp Neurosciences Inc. sees therapeutic potential in what was previously considered a throw-away molecule: the R(+) enantiomer of Mirapex pramipexole, which Knopp calls KNS-760704. In two weeks, the compound will enter Phase II trials for amyotrophic lateral sclerosis (ALS).

Boehringer Ingelheim GmbH markets Mirapex pramipexole, a dopamine receptor agonist, to treat Parkinson's disease (PD) and restless legs syndrome (RLS).

While pramipexole and KNS-760704 have the same chemical composition, a small difference in physical structure causes the former to have a high affinity for the dopamine receptor and the latter a low affinity. The difference provides the window of opportunity for Knopp.

Pramipexole is a benzothiazole, and as an S enantiomer, the N, propyl amino group attached to the benzene ring is oriented to the left. The R(+) enantiomer of pramipexole has the N, propyl amino group oriented to the right.

According to President and CEO Michael Bozik, Mirapex is purified by eliminating the R(+) enantiomer during manufacturing because it doesn't stimulate dopamine. "This is why no one knew about the R(+) enantiomer. It was thought to be a throw-away molecule," he said.

Jim Bennett, professor of neurology in the department of neurology and Center for the Study of Neurodegenerative Diseases at the University of Virginia School of Medicine, retrieved the molecule from the trash.

Bennett was a principle investigator during the development of Mirapex. When...

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