STAR ALLIANCE PARTNERS
The CMTA’s alliances with key players in the pharmaceutical, biotechnology and research service industries, along with non-profit research organizations and the National Institutes of Health, are a critical part of its STAR initiative to rapidly deliver therapies to CMT patients. Each alliance is integrated into the efforts of the CMTA Disease Project Teams, where it participates in a CMTA consortium effort with shared goals, resources and know-how.
The CMTA’s key alliance partners are:
Genzyme (a Sanofi Company)
In September 2014, the CMTA entered an alliance with Genzyme, a Sanofi company, in which the STAR network of investigators are able to leverage the capabilities of the Sanofi U.S. high-throughput screening facility in Tucson, Arizona together with the expert drug development capabilities of Genzyme. Assays developed at the University of Wisconsin and the NIH have been used to screen compound libraries that include close to 2 million small molecules. The aim is to identify novel small molecule modulators of PMP22 that can advance to drug development. Additional investigative STAR participants include laboratories at the University of Iowa and University of Buffalo, which are participating via the sharing of assays specific to the regulation of PMP22 in peripheral nerves. Preclinical investigation of the in vivo activity of select molecules will be pursued in laboratory models of CMT1A through the CMTA’s earlier announced service relationship with PsychoGenics.
In October 2014, the CMTA entered a collaboration with Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, to evaluate the pharmacology of ADX71441, a GABA-B receptor positive allosteric modulator (PAM), in preclinical models of CMT1A. The alliance team is evaluating the efficacy of ADX71441 as a pharmacological agent in preclinical models of CMT1A. The potential of ADX71441 to impede the development of motor and sensory control defects associated with normal disease progression is being assessed at PsychoGenics.
In April 2015, the CMTA entered into an alliance with Affectis Pharmaceuticals AG to evaluate the efficacy of advanced Affectis compounds in preclinical models of CMT1A. Affectis is a therapy development company and, since 2013, a fully owned subsidiary of the Lead Discovery Center GmbH (LDC), a spin-off of Max Planck Innovation GmbH. Its collaboration with the CMT1A Disease Project Team aims to demonstrate the potential of P2X7 antagonists that have high potency for the human form of P2X7 and are orally bioavailable in treating CMT1A. Use of such antagonists may impede the development of motor and sensory control defects associated with progression of the disease. The potential of ADX71441 to impede the development of motor and sensory control defects associated with normal disease progression is being assessed at PsychoGenics.
Neusentis (a Pfizer Research Unit)
Neusentis is a biopharmaceutical company focused on the discovery and development of novel small molecule drugs that modulate ion channel targets. The CMTA is currently working with Neusentis to validate potential targets for a CMT1A therapy. These potential targets were identified in screening of a compound set at the NIH, using a cell-based gene reporter assay that measures changes in the expression of PMP22.
PsychoGenics is a leader in specialty preclinical contract research and drug discovery services, with a focus on neurodegenerative and psychiatric disorders. PsychoGenics’ proprietary technologies are developed to facilitate high-throughput, in vivo, compound testing. In 2013, the CMTA completed a master services agreement with PsychoGenics to provide biomarker and behavioral testing support to the STAR network. The company works closely with the CMTA to design and then execute preclinical drug testing studies in CMT animal models on its behalf. They have additionally been instrumental in characterizing animal models destined for use in the research efforts of STAR Disease Project Teams.
HumanFirst Therapeutics LLC
HumanFirst Therapeutics is a Research Consulting & Management Company founded with the aim of helping organizations identify Therapy Development Projects and then assembling the teams, funding and management needed to progress them to the clinic. It seeks to develop a measurable value for therapeutics projects that make them attractive candidates for partnering and investment. HumanFirst Therapeutics aids the CMTA in developing its research strategy and alliances, and provides operational expertise in organizational development and project team management, as well as preclinical and medicinal chemistry direction.
Horizon Discovery is a translational genomics company that develops and supplies patient-relevant drug discovery and diagnostic research tools, including contract research services. Horizon Discovery has worked closely with STAR investigators to design and create several new rodent models of CMT, which are currently being characterized in the CMTA STAR alliance network.
Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic laboratories improve and expedite the discovery, early-stage development of new drug therapies for the patients who need them. This global provider of contract animal research services is working with the CMTA to breed, cryopreserve and distribute rodent models of CMT that are used in the STAR alliance network.
The Jackson Laboratory
The Jackson Laboratory is an independent, nonprofit organization focusing on mammalian genetics research to advance human health. It is the leading nonprofit provider of mouse genetics and breeding services. The Jackson Laboratory is working with the CMTA to breed and distribute specialized mouse models of CMT in support of the research efforts of STAR teams in the CMTA alliance network.
New York Stem Cell Foundation
In December 2014, the CMTA announced a collaboration with the New York Stem Cell Foundation (NYSCF) Research Institute to develop a bank of induced pluripotent stem cell (iPSC) lines for a variety of neuropathy disorders of known genetic causation. The NYSCF is making stem cells lines from Charcot-Marie-Tooth patient materials that have been curated in a biobank assembled at the University of Iowa. Utilizing its automated technology, the NYSCF Global Stem Cell ArrayTM, NYSCF will systematically generate iPSC lines from tissue samples obtained from patients and representing a number of CMT disease states. These cell lines will then be used to develop methods for creating differentiated cells that mimic the myelin-producing Schwann cells that are defective in Type 1 Charcot-Marie-Tooth (CMT) disorders of peripheral nerve, as well as the motor and sensory neurons that are defective in Type 2 disorders.
The National Institutes of Health (U.S.A.)
The National Institutes of Health (U.S.A.) is this nation’s premier medical research agency—supporting scientific studies that turn discovery into health solutions. The CMTA has close working relationships at the NIH with the National Center for Advancing Translational Sciences (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS), and the NIH Office of Technology Transfer.
The CMTA is sponsoring research at NCATS to design cell-based high throughput screening assays that can be used to identify modulators of the molecular defect associated with a CMT disease pathology. In addition, the CMTA provides support to an NIH-funded project that has used a PMP22 reporter assay to screen a chemical libraries of ~400,000 small molecules at NCATS.
Going from the lab bench to the bedside, NINDS provides funding and guidance to the Inherited Neuropathies Consortium, with support also provided by the CMTA. This NIH consortium of Clinical Centers has assembled a registry of 7,000 CMT patients, and is actively working to perform natural history studies of CMT diseases, and evaluate instruments that may be useful in measuring disease progression. In addition, NINDS provides research support to many of the STAR investigator laboratories.