Rodin’s targeted epigenetic approach to synaptic resilience is relevant in multiple phenotypically diverse diseases, which all share the common root cause of impaired neuronal and synaptic function. Disease areas of focus include:
Rodin Therapeutics is working to discover and develop epigenetic modulators of synaptic resilience for the treatment of cognitive and functional impairment due to Alzheimer’s disease (AD), one of the most significant public health problems of the 21st century. The number of AD patients in the US is estimated at 5.2 million and projected to double by 2050, and the overall cost of care for these patients is projected to reach $1.2 trillion by 2050 (Alzheimer’s Association 2013).
There is a pressing need to develop better therapies to relieve the cognitive and functional impairments of AD, reducing caregiver burden, cost of care, and delaying the institutionalization of AD patients. Our lead program is focused on enhancing synaptic health and function, which has been shown to be a major cause of memory impairment in AD patients.
Rodin Therapeutics is also investigating the role of HDAC inhibition in the cognitive dysfunction associated with Parkinson’s disease (PD). Cognitive impairments are a common and life-altering symptom of PD that is not addressed by standard motor therapy. Rodin is also working to develop safe and effective HDAC inhibitors for PD dementia. By enhancing the function of remaining synapses in the PD brain, Rodin compounds may improve cognition and/or slow cognitive decline. Moreover, through the inhibition of HDACs, Rodin compounds may have an impact on the course of the disease by protecting still functioning neurons from ex-nigro-striatal neurodegeneration.
There are multiple other neurological disorders that could benefit from improved synaptic function through targeted epigenetic regulation, e.g.:
- Memories of a traumatic event can cause feelings of grief, guilt, or loss, as well as negative emotional responses such as anger, rage or aggression. However, a memory can be modified to reduce the negative associations and stressful reactions to it, and HDAC inhibitors have already demonstrated the ability to lessen fearful memories in animals (Graff et al., 2014). Rodin is investigating whether our safe, selective HDAC inhibitors can reduce not only the immediate effects of trauma but also prevent or reduce the development of later disease, including Post Traumatic Stress Disorder (PTSD).
- Traumatic brain injury (TBI) is associated with cognitive, social, emotional, and behavioral symptoms. There is evidence for increased histone acetylation (Wong et al. 2016) and synaptic degeneration (Gao et al. 2011) in animal models of traumatic brain injury. Pan-HDAC inhibitors can decrease inflammation and injury in rat and mouse models of TBI (Shein et al. 2009, Dash et al. 2010, Wang et al. 2013).
- The pathophysiology of Rett syndrome is also thought to be mediated by epigenetic changes. In addition, Rett patients show alterations in dendritic spine structure (Xu et al. 2014) and deficits in synaptic proteins involved in synaptic signaling such as BDNF (Katz 2014), which could be reversed by Rodin’s HDAC inhibitors.