LRRK2 – novel Target for Parkinson’s Disease and Parkinson-related Syndroms

Reference Number TO 01-00631

The Challenge

Parkinson's disease (PD) is a severe, progressive, neurodegenerative disorder affecting approximately 1-2% of the population aged 65 and older in the U.S. and Europe, the incidence increasing with age. Current therapies are symptomatic and not effective at halting or significantly slowing the disease progress. The search for etiologic-based therapies has focused largely on genetic findings made in familial forms of this disease. Mutations of five genes, including LRRK2 (leucine-rich repeat kinase 2), have been unequivocally linked to PD. Because the clinical phenotype ensuing from LRRK2 mutations resembles idiopathic PD, LRRK2 has emerged as the most relevant player in PD pathogenesis.

Technology

In a joint effort (see below) LRRK2 was identified in families with late-onset autosomal dominant PD. Several new LRRK2 mutations has been described (R793M, Q930R, S1096C, L1114L, I1122V, S1228T, R1441C, Y1699C, I2020T) and linked to specific families. Clinical and pathological studies have demonstrated that in the majority of cases LRRK2 mutations lead to PD with classical clinical and pathological features. However, in some patients the pathological features can be distinct and/or more extensive than typically seen in PD. Mutations in the kinase domain and the GTPase domain increase kinase activity. Such, LRRK2 may present as a future target for pharmacological interference via protein kinase inhibitors.

Commercial Benefit and Advantages
LRRK2 is a promising point of therapeutic intervention for PD and its genetic diagnosis. Multiple lines of evidence suggest that LRRK2 is key to understanding the etiology of PD. Thus far, the mutations found from this work accounts, with some other reported LRRK2 mutations, for up to 10% of familial PD and for a significant fraction of sporadic PD cases.

Developmental Status
Structural and functional analyses including kinase activities, cellular structures (cytoskeleton) and pathogenesis in mouse models have been performed and are ongoing.

Partnering Opportunity
Ascenion offers a variety of licensing options and collaborative development opportunities with the Helmholtz Zentrum München, the University Hospital Tübingen and the Mayo Clinic College of Medicine.Especially, we are offering- a license covering the diagnostic use of the LRRK2 gene and its mutations- monoclonal antibodies against LRRK2 and GST-tagged protein domains, and expression vectors for LRRK2 domains

Patent situation
Patent applications are pending in US, CA, EP, and AU. A patent covering another mutation (G2019S) is issued in US (7,544,786) and further patent applications are pending in CA, EP, and AU and would also be available for licensing.

Relevant Publication
Mata et al. (2006), Trends Neurosci. 29, 286-293; Taylor et al. (2006), Trends Mol. Med. 12, 76-82; Gloeckner et al. (2006), Hum. Mol. Genet. 15, 223-232; Zimprich et al., Neuron. 2004 Nov 18;44(4):601-7.