Frontotemporal Dementia (FTD)
Frontotemporal dementia (FTD) refers to a group of diseases caused by the progressive loss of nerve cells in the frontal or temporal lobes of the brain. With our pioneering efforts in FTD research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of FTD. As your reliable partner in FTD research, we offer unmatched support to fulfill your scientific research needs.
Overview of FTD
FTD encompasses several subtypes, including behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), progressive nonfluent aphasia (PNFA), and rare variants such as neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). FTD primarily affects individuals in late adulthood, typically between the ages of 45 and 65, although it can occur in younger or older individuals. The overall prevalence is 15-22 persons/100,000 population.
FTD encompasses multiple subtypes and the pathogenesis involves various genetic and molecular mechanisms. Mutations and genetic variations in genes like MAPT, GRN, and C9orf72 have been identified as significant factors in the development of FTD. These genes play crucial roles in protein aggregation, cellular transport, and synaptic function.
Fig. 1 The three main types of FTD pathology are characterized by the accumulation of distinct protein aggregates. (Hock, et al., 2016)Diagnostics Development of FTD
Diagnostic approaches for FTD mainly involve neuroimaging examination and genetic testing. These methods aim to differentiate FTD from other neurodegenerative disorders and identify specific subtypes of FTD.
Neuroimaging Examination
Neuroimaging, including magnetic resonance imaging (MRI) and positron emission tomography (PET), plays a crucial role in detecting structural and functional changes in the brain associated with FTD. MRI can reveal atrophy and patterns of degeneration in the frontal and temporal lobes, while PET imaging can assess abnormal protein deposition.
Genetic Testing
Genetic testing has enabled the identification of specific genetic mutations associated with FTD. Genetic screening can help confirm the diagnosis, provide valuable prognostic information, and guide genetic counseling for affected individuals and their families.
Therapeutics Development of FTD
FTD currently has no cure or FDA-approved medications. However, symptomatic therapies may involve using Alzheimer's and antidepressant drugs like cholinesterase inhibitors and selective serotonin reuptake inhibitors. Research aims to develop therapies that target FTD's molecular mechanisms, addressing protein aggregation, neuroinflammation, and neuronal survival.
- Targets of FTD Therapy Development
| Target | Description |
|---|---|
| Tau Protein and Microtubule Stabilization | In FTD, pathological changes in the tau protein result in the formation of insoluble aggregates called tau tangles. These tangles disrupt neuronal function and cause neurodegeneration. Developing FTD therapies involves targeting tau protein aggregation, promoting tau clearance, and stabilizing microtubules. |
| Protein Homeostasis and Cellular Clearance Mechanisms | In FTD, disruptions in protein homeostasis contribute to the accumulation of abnormal protein aggregates, such as tau, TDP-43, and FUS. Therapeutic approaches aim to enhance cellular clearance mechanisms responsible for removing these toxic protein aggregates. Modulating autophagy is an effective strategy. |
| Neuroinflammation and Immune System Modulation | Neuroinflammation, characterized by immune cell activation and the release of inflammatory molecules in the brain, is a notable characteristic of FTD. Anti-inflammatory agents and immunomodulators are expected to reduce the damaging effects of neuroinflammation in FTD. |
- Types of FTD Therapy Development
Gene-based therapies hold promise for FTD by targeting specific genetic mutations associated with the disease.
- Gene replacement therapy: Utilizing viral vectors or other delivery systems to introduce functional copies of mutated genes or missing genes into affected cells, restoring normal protein expression and function.
- Gene silencing therapy: Using RNA-based therapies, such as small interfering RNA (siRNA) or antisense oligonucleotides (ASOs), to selectively silence or reduce the expression of disease-causing genes, thereby mitigating their pathological effects.
Our Services
As a frontrunner in the field of biological research and CRO services, our company is dedicated to offering holistic solutions for the diagnostics development and therapy research of FTD. Through collaborations with industry experts, we have established an all-encompassing platform for rare diseases to facilitate FTD therapy development.
Platforms of FTD Therapy Development
Animal Models of FTD
Recognizing the significance of dependable animal models in FTD disease research, our company is committed to offering animal model development services that facilitate preclinical research and aid in drug discovery endeavors.
| Genetically Engineered Models | ||
|---|---|---|
| Gene targeting and manipulation techniques, such as gene knockouts or knock-ins, are employed to introduce specific mutations associated with FTD into the animal genome. Our company specializes in utilizing the powerful CRISPR/Cas9 gene editing technology to create highly accurate and reliable FTD animal models. | ||
| Optional Models |
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| Viral Vector Models | ||
| Viral vector-based models provide an alternative method of modeling FTD-associated gene mutations in animals. We specialize in using adeno-associated viruses (AAV) to deliver mutated forms of tau or progranulin into the mouse brain. This approach results in the formation of tau aggregates or progranulin deficiency in specific brain regions, respectively, leading to neurodegeneration and behavioral abnormalities similar to FTD. | ||
| Optional Models | Tau Models | |
| Optional Species | Mice, Rats, Non-human Primates, Zebrafish, Fruit Flies, Caenorhabditis Elegans, Others | |
With complete animal species resources, we can meet your diversified preclinical research including drug safety evaluation and pharmacokinetic analysis. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.
References
- Greaves, Caroline V., and Jonathan D. Rohrer. "An update on genetic frontotemporal dementia." Journal of neurology 266.8 (2019): 2075-2086.
- Hock, Eva‐Maria, and Magdalini Polymenidou. "Prion‐like propagation as a pathogenic principle in frontotemporal dementia." Journal of Neurochemistry 138 (2016): 163-183.
- Roberson, Erik D. "Mouse models of frontotemporal dementia." Annals of neurology 72.6 (2012): 837-849.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
