NEURODEGENERATIVE DISORDERS

The exact disease ethology of most neurodegenerative disorders is still unknown, but the hallmarks of such is a build up of toxic proteins in the brain, leading to cell death of neurons or glia in certain regions of the brain associated with the specific disease. As many as one in five people over the age of 65 worldwide will have some form of neurodegenerative disorder by 2030.

Prediction BioSciences is working on therapeutic solutions to resolve and improve the quality of life of patients suffering two frequent neurodegenerative disorders as Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS).
More than 50% of FTD cases are familial and belong to behavioral variant FTD (bvFTD), mainly caused by mutations in grn or c9orf72 genes:

Neurodegenerative disorders

Frontotemporal dementia (FTD)

Frontotemporal dementia is a severe and fatal disease of the brain characterized by progressive and massive loss of neurons in the frontal and temporal lobes. This nervous tissue damage leads to deterioration in behaviour, personality and speech impairment. FTD is the second most common type of dementia following Alzheimer´s disease and the age range of onset is 40-60 years. It is caused by protein aggregation within neurons and glial cells, which affects their functionality.

GRN GENE MUTATIONS

This gene codes for a secreted growth factor-like protein called Progranulin (PGRN), which is produced by neurons and glial cells. GRN is a key regulator of microglia function in the brain with neuroprotective and antiinflamatory properties. Mutations in grn gene lead to a drop in Progranulin´s levels and have been associated with the development of FTD in 90% of the cases.

c9orf72 GENE MUTATIONS

Mutations in this gene have been associated with TDP-43 protein aggregation leading to FTD with behavioural disorders in the majority of cases (50-70%).

Frontotemporal dementia behavioral variant (50-70%)
NO SPECIFIC TREATMENTS FOR FTD

Currently there are no specific treatments for FTD, only medications that can reduce the impact of the FTD symptoms and improve quality of life.

OUR SOLUTION – NEURODEGENERATIVE DISORDERS – FTD

Engineered neural exosomes

loaded with nucleic acid vectors against proprietary targets

FTD is a severe and fatal disease of the brain characterized by massive loss of cortical neurons. A deficiency in the secreted growth factor Progranulin (PGRN) was found to be causative for a specific subtype of FTD, the behavioral variant FTD (bvFTD). In recent years, evidence increased for the involvement of GRN deficiency in other neurodegenerative diseases as Parkinson’s Disease and even Alzheimer’s Disease.

NOVEL RECEPTORS FOR PGRN

PGRN is a secreted protein, coded by GRN gene, with roles in tumorigenesis, inflammation, and neurobiology. Various functions have been proposed for PGRN in the periphery (e.g. inflammatory processes) but not much is known about the mechanisms or signal transduction pathways controlled by this protein, especially in the brain.

However, it is frequently associated with proliferation, migration, and survival underlining the connection of PGRN to cancer. A strong up regulation of PGRN expression can be seen in gliomas, the most malignant form of brain tumors. For a potential development of a FTD therapeutic it is of great importance to find a highly specific molecule that can operate as PGRN replacement without promoting its tumorigenic properties and supporting the development of cancer.

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“Prediction is developing an exosome-based platform that is brain cell-type specific to deliver a therapeutic cargo to our disease-modifying targets.”

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NEURODEGENERATIVE DISORDERS

Amyotrophic lateral sclerosis (ALS)

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects motor neurons both in the brain and the spinal cord. This damage in the motor neurons results in a progressive muscle weakness or wasting, that can finally cause general paralysis and difficulties for swallowing and breathing.

The age range of onset is 40-70 years. As it happens in FTD, protein aggregates of Tau, ADP-43 and SOD are the responsible for motor neurons damage in ALS.

The current treatment of this disease is focused on the management of symptoms to slow down the disease´s progression.

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