A research study led by Dr Alireza Faridar and Dr Stanley Appel at the Houston Methodist Neurological Institute has demonstrated the involvement of the peripheral immune system in the neuroinflammatory profile of frontotemporal dementia (FTD). 

Dr Fred Grossman, Chief Medical Officer at sponsors Coya, said: “We believe these biomarker data coupled with the clinical and lab results of the clinical study in FTD provide additional evidence supporting the development of biologic combination therapies that enhance the function of regulatory T cells (Tregs) and target inflammation in FTD, ALS and other neurodegenerative diseases of high unmet need.” 

Coya’s investigational product candidate pipeline aims to restore the anti-inflammatory and immunomodulatory functions of Tregs. Its therapeutic platforms include Treg-enhancing biologics, Treg-derived exosomes, and autologous Treg cell therapy. 

Blood samples were obtained from 27 patients clinically diagnosed with FTD and 25 age-matched healthy individuals as a control group. Comprehensive analyses revealed significantly lower regulatory Treg immunomodulatory suppressive function in FTD patients compared to healthy controls. Transcriptomic profiling of monocytes showed different degrees of dysregulation of immune-related genes in samples from FTD patients.  

Consistent with the reduced anti-inflammatory function observed in Tregs, proteomic analysis of plasma inflammatory mediators showed a significant increase in the pro-inflammatory cytokine TNFα (tumour necrosis factor-alpha) and the chemokines CXCL10, CCL3, CCL19, CSF1 and CXCL12 in FTD patients compared to healthy controls. 

The immunomodulatory function of Tregs 

The company believes the results of this study demonstrate that there is a dysregulation of inflammation-related gene expression in peripheral monocytes and an increase of plasma inflammatory chemokines and cytokines in FTD. In addition, the data provide evidence of compromised immunomodulatory function of Tregs. 

The company argues that this study further supports the previously reported findings of an academic clinical study of low-dose interleukin 2 (LD IL-2) and CTLA-4 Ig in patients with FTD. The subcutaneous administration of LD IL-2 and CTLA-4 Ig significantly increased the number and function of Tregs as early as two weeks after initiation of treatment and remained elevated throughout the study. Study patients did not show clinical cognitive decline as measured by the validated tools MoCA (Montreal Cognitive Assessment) and CDR-FTLD (Clinical Dementia Rating-Frontotemporal Lobar Degeneration module) over the 22-week treatment period. 

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