Frontotemporal Lobe Dementia Drug Discovery Service

Creative Biolabs is a leading international biotechnology company, we believe in the transformative power of science and technology. We believe that creating and developing innovative and differentiated one-stop solutions will greatly advance your progress in drug development for frontotemporal lobar degeneration (FTD)

Overview of FTD

Once considered a rare disorder, FTD is now recognized as a common cause of early-onset dementia. FTD encompasses a range of related neurodegenerative disorders, including behavioral, motor, and language phenotypes, for which there is currently no effective treatment. Creative Biolabs has built a comprehensive technology platform that will provide you with a full range of in vitro and in vivo services in FTD research

Biomarkers of FTD

Biomarkers can provide evidence confirming that a particular therapeutic candidate engages its intended target and exerts the predicted physiological effect. CSF measures total tau, tau that is phosphorylated at threonine 181 (pTau₁₈₁) and amyloid-β_1-42 (Aβ_1-42) are the most promising biomarker candidates for the differentiation of FTD from AD. CSF levels of progranulin and NfL are promising candidate biomarkers of TDP43- mediated neurodegeneration in ALS150, and could therefore be helpful in the identification of TDP43- mediated FTD.

Drug Development Services for FTD

Success in drug development for neurodegenerative diseases depends not only on an in-depth understanding of the brain mechanisms and course associated with the disease but also on the development of specific tools (animal models, libraries of compounds, etc.) that are not readily available to all researchers. Examples of such tools include: the identification of novel targets, standardized dynamic (vs. static) animal models, validated disease progression, and target engagement biomarkers (as endpoints and for dose finding). The understanding of the molecular etiology of FTD is mature enough to create a variety of drug targets, animal models, and early compounds that can be tested in human clinical trials.

Targets for FTD Based on Mechanisms of Disease

The two main underlying pathologies of FTDs are TPD43 proteinopathy and tauopathy. A better understanding of the mechanisms of neurodegenerative verticillium wilt offers many possible targets for tau drug discovery. By inhibiting the phosphorylation of tau, the formation of NFTs might be retarded and MTs could be stabilized by increasing levels of non-phosphorylated tau. Several candidate kinases may be good drug targets.

• Glycogen Synthase Kinase (GSK3) 3-beta (GSK3beta)

GSK3 phosphorylates tau and hence could be the target for inhibition to prevent pathological tau phosphorylation in AD and FTD tauopathies.

• Cyclin-dependent Kinase 5 (CKD5)

CDK5 phosphorylates tau at several sites associated with the disease and may be an ideal target for drug discovery because it maintains its active form not by phosphorylation but by binding to a protein chaperone called P25

• Heat Shock Proteins (HSPs) and the Ubiquitin Proteasome System

The ubiquitin ligase carboxy terminus of Hsp70 interacting protein (CHIP) can polyubiquitinate tau and may play a crucial role in preventing the accumulation of phospho-tau and NFTs

• Inhibitors of Fibrillization
• MT Stabilizing Agents
• Neuroprotective Therapies for FTDs

Pharmacological Treatments for FTD

Genetic forms of FTD may be particularly attractive candidates for targeted therapies because of the potential for presymptomatic disease detection. Selective serotonin reuptake inhibitors (SSRIs) have been used with a degree of success in FTD patients. The activity of trazodone is mainly based on postsynaptic 5-HTA/2c antagonism, and its metabolites act as 5-HT1A agonists and moderate selective serotonin reuptake inhibitors. New therapies may focus on targets related to the pathogenesis of the disease, which may be different for different subtypes of FTD. Agents that prevent the expression or accumulation of tau represent a future direction of therapy.

Fig.1 Potential therapeutic interventions for FTlD. (Panza, et al., 2020)

As with other neurodegenerative disorders, a major goal of future FTLD research is to translate the increasing understanding of pathogenesis into effective treatments that will slow, halt or ultimately prevent this devastating disease. Every stage of drug development affects the end result and increases the cost. At Creative Biolabs, we have the expertise to optimize each stage of FTD research to ensure that you get the results you want and achieve the highest level of efficiency. Do not hesitate to contact us to promote your project.

Reference

1. Panza, F.; et al. Development of disease-modifying drugs for frontotemporal dementia spectrum disorders. Nature Reviews Neurology. 2020, 16(4): 213-228.