Amyloidosis is a collective name for various diseases, including Alzheimer's disease, Parkinson's disease and several prion-related diseases. In all cases, so-called amyloid deposits of a protein are found which, by assuming an incorrect folding, aggregate into fiber-like structures. Amyloid formation of the protein transthyretin (TTR) is associated with several different diseases. These include senile systemic amyloidosis, pregnancy poisoning and familial amyloidosis with polyneuropathy (FAP). In FAP, a mutation makes it easier for the protein to assume an incorrect fold. FAP is found all over the world but is more common in northern Sweden (also known as Skellefte's disease), Portugal and Japan.
The protein TTR is synthesized in the liver, brain and eye and is therefore present in the blood, cerebrospinal fluid and vitreous. Consequently, some FAP patients develop eye problems with clinical phenotypes such as amyloids in the vitreous, corneal dystrophies, open-angle glaucoma, darkening of the lens capsule, and damage to the optic nerve.

The aim of this study is to investigate whether CRISPR/Cas9-based gene therapy can modify the TTR gene and thus, reduce the expression of the TTR protein in the eye of C57BL/6 mice. The gene delivery will based on non-viral system with Lipid Nanoparticles injected intravitreally. The toxicity and effects of the therapy will be evaluated in PCR, WB and immunostainings, and retinal function will be assessed with electroretinography.

Conceição I, González-Duarte A, Obici L, Schmidt HH, Simoneau D, Ong ML, Amass L. "Red-flag" symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016 Mar;21(1):5-9. doi: 10.1111/jns.12153. PMID: 26663427