Galenea Corp. and CHDI Foundation, Inc. announce the extension and expansion of their collaboration to further characterize the synaptic dysfunction apparent in Huntington’s disease (HD) utilizing Galenea’s proprietary synaptic transmission drug discovery platform. Galenea’s innovative platform is providing significant new insights into the disease mechanism, and the collaboration will now focus on extending these findings in order to specifically target this mechanism to discover novel therapies for HD.
“As we and CHDI had anticipated, our platform is well suited to unraveling the synaptic dysfunction in HD and – ultimately – the discovery of synaptic-based therapeutics,” said David Gerber, PhD, VP of CNS Research at Galenea. “We are very pleased with CHDI’s decision to extend and expand our collaboration. The findings in the first phase of work were very compelling, and we see the potential for completely new approaches to this devastating disease.” Mark Benjamin, DSc, Galenea’s President and CEO added, “CHDI’s scientific leadership in this area and the inclusion of their new animal models of HD will greatly enhance the program.”
Dysfunctions in synaptic transmission, the fundamental process by which neurons communicate, play a critical role in many central nervous system diseases, including HD. Mutant huntingtin protein, the causative defect in HD, appears to disrupt normal synaptic function, contributing to the behavioral, cognitive, and motor symptoms of this neurodegenerative disorder. Galenea’s platform targets synaptic transmission on multiple levels. The MANTRA (TM) (Multiwell Automated Neuro TRansmission Assay) system, a novel high-throughput screening technology, directly monitors synaptic events at the cellular level in primary neuronal cultures. At the network level, Galenea has developed a state-of-the-art system to establish in vivo electroencephalography (EEG) measures of behaviors in rodent disease models by monitoring brain and behavioral activities in parallel. The collaboration has employed this two-pronged approach to characterize the synaptic defects that occur in HD at both the neuronal and network levels, which may explain some critical features of the disease. The first phase of the collaboration led to the discovery of alterations of synaptic vesicle dynamics in cortical synapses from HD cellular models and in cortical EEG measures in HD animal models.
“We have been very impressed with Galenea’s technology and expertise,” said Ramee Lee, PhD, Director, Early Discovery Initiative at CHDI. “The collaboration has yielded new insights into the cellular causes of synaptic dysfunction in HD that are not accessible by other means. We now see changes in synaptic function in multiple models of HD, using both MANTRA assays and rodent EEG readouts, and these changes occur prior to the onset of synaptic loss.” George Yohrling, PhD, Director, Target Assessment at CHDI added, “This second phase of our collaboration with Galenea will focus on understanding whether there is a polyglutamine-length dependency to the observed synaptic alterations and on building a broad HD drug-discovery platform through the application of these novel findings. By determining the applicability of these synaptic and network changes, we will develop critical in vitro and in vivo screening tools to identify either small molecules or biological pathways that can ameliorate the synaptic effects of mutant huntingtin.”
About Huntington’s Disease
Huntington’s disease is an inherited neurodegenerative disorder caused by the expansion of a DNA sequence called a CAG repeat within the huntingtin gene. Each child of a parent with this mutation has a 50% chance of inheriting it, and in those who do inherit the mutation, brain cells progressively degenerate leading to behavioral, cognitive, and motor impairments that, over the course of the disease, significantly reduce quality of life. The disease ultimately results in death within 15 to 25 years of overt symptom onset. It is estimated that about 30,000 people are affected by HD in the United States and at least 150,000 others have a 50% risk of developing the disease in the future. There are currently no approved therapies that slow the progression of Huntington’s disease.
About CHDI Foundation, Inc.
CHDI Foundation, Inc. is a privately-funded, not-for-profit, biomedical research organization exclusively dedicated to rapidly discovering and developing therapies that slow the progression of Huntington’s disease. As a collaborative enabler, CHDI seeks to bring the right partners together to identify and address critical scientific issues and move drug candidates to clinical evaluation as quickly as possible. Our scientists work closely with a network of more than 600 researchers in academic and industrial laboratories around the world in the pursuit of these novel therapies, providing strategic scientific direction to ensure that our common goals remain in focus. More information about CHDI can be found at www.chdifoundation.org .
Galenea is a leader in the rapidly emerging field of synaptic transmission drug discovery. Synaptic transmission is the process by which neurons communicate with each other, and dysfunctions in this process are now known to play a central role in many psychiatric and neurological diseases. Modulators of synaptic transmission therefore have the potential to yield breakthrough treatments. Galenea has developed an innovative synaptic transmission drug discovery platform that integrates three components: the MANTRA(TM) system, a proprietary, high throughput screening technology, developed with Cellectricon AB of Molndal, Sweden, to identify a new generation of small molecule modulators of synaptic transmission; preclinical network measures employing in vitro brain slice EEG assays, and in vivo models using integrated EEG measures of animal behavior to more reliably determine CNS drug efficacy; and human EEG biomarkers, developed in tandem with and informed by our animal EEG data to greatly enhance CNS drug development. The company is advancing a novel pro-cognitive program derived from the platform and the approach can be extended to address multiple CNS disorders. Based in Cambridge, MA, Galenea has assembled a compelling scientific team, balancing academic aptitude with industry experience and entrepreneurship. For more information about Galenea, please visit the company’s website at www.galenea.com