Press Release

11/05/2014

Amyotrophic lateral sclerosis (ALS): Toponome-based therapy principle successful in clinical phase II trial

By overcoming the spectral resolution limit using an imaging cycler microscope® (ICM) it was possible to resolve an 18-dimensional molecular system in ALS peripheral blood mononuclear cells in 1999 as described in several international patents (1-3). This molecular system, referred to as the ALS toponome, is hierarchically organized and revealed CD16 (FcγRIII) as lead protein and therapeutic target (1-3). As recently reported, targeting CD16 shows downregulation in a phase I clinical trial (4) and beneficial effects in 30% of ALS patients with stop of disease progression in a phase II clinical trial (5). This proof of concept confirms the predictive power of ICM used in toponome-based drug discovery, and shows that parameter-unlimited ICM imaging in intact human tissues is a reliable condition for correct drug target prediction.

References:

  1. Schubert W. (1999). “Method of blocking cytotoxic activity in patients with amyotrophic lateral sclerosis using antibodies to FcγRIII”. US patent no. US 6,638,506 (first published as international patent application WO 99/29731, 1999).
  2. Schubert W. (2001a). “Method of blocking cytotoxic activity in patients with amyotrophic lateral sclerosis using protein V”. US patent no. US 6,638,515
  3. Schubert Walter (2001b). “Method of blocking cytotoxic activity in patients with amyotrophic lateral sclerosis using soluble FcγRIII receptors”. US patent no. US 6,649,165
  4. Miller, Robert G.; Zhang, Rongzhen; Block, Gilbert; Katz, Jonathan; Barohn, Richard; Kasarskis, Edward; Forshew, Dallas; Gopalakrishnan, Vidhya; McGrath, Michael S. (2014). “NP001 regulation of macrophage activation markers in ALS: A phase I clinical and biomarker study”. Amyotroph Lateral Scler Frontotemporal Degener. Sep 5:1-9. doi:10.3109/21678421.2014.951940
  5. Goyal, Namita A.; Mozaffar, Tahseen (2014). “Experimental trials in amyotrophic lateral sclerosis: a review of recently completed, ongoing and planned trials using existing and novel drugs”. Expert Opinion on Investigational Drugs. 23(11): 1541-51. doi: 10.1517/13543784.2014.933807


Contact:

Human Toponome Project
Molecular Pattern Recognition Research Group
+49-391-6117175
Toposnomos@gmx.de