Stage 1. Drug Repurposing

Unravel Biosciences. To help us rapidly find a repurposed drug which can help Aria. This is the fastest short term project which we hope will yield viable safe drugs (already FDA approved for other diseases) or known molecules we can use to treat Aria, to help reduce the progression of mito.

About Unravel :

Unravel brings effective drugs to patients based on technology developed at the Wyss Institute for Biologically Inspired Engineering at Harvard University. Their deep experience cuts across disciplines, including computational drug discovery, innovative animal models, automated drug screens, and entrepreneurship, and forms the keystone to building a new paradigm for accelerating drug development at lower cost and with lower risk.

https://www.unravel.bio/

Stage 2. Drug Screening

Unravel Biosciences will then integrate in vivo screening and clinical validation of discovered targets.

Evaluating drug candidate efficacy and safety can be a bottleneck for traditional workflows. Unravel screens drug candidates in CRISPR-engineered tadpoles that serve as patient avatars. We are able to evaluate whether drug candidates work using clinically-relevant metrics like motor function, behaviour, seizures, sleep, and cognition. The SquishyWare™ in vivo screening platform is customized for one or more disorders of interest in as little as 3 weeks. Unravel partners to develop patient-derived iPS lines for in vitro screens. Using in silico-predicted drug candidates has a 40% hit rate. Being more than 200x better than traditional screening, in silico predictions drastically limit the number of candidates necessary to screen compared to other methods, resulting in faster, less expensive studies.

Stage 3. Better Diagnosis

Charles River Laboratories

The NHS has left us with a clinically incomplete diagnosis according to the industry we have contacted.

We want to explore other treatments such as Antisense Oligonucleotides (ASO) therapy. ASO therapy is a promising new treatment option we want to explore. On reaching out to global centres they could not progress our enquiry because they did not feel the NHS has done enough work on Aria’s genetics. Not sufficient to access this treatment. So your funds will be spent on a project with Charles River, where they will look to see if Aria’s LONP1 mutation is a “gain-of-function” or “loss-of-function” mutation. It has been hypothesised by Dr David Fischer of Charles River Laboratories that the mutated allele could be “poisoning” the other good allele. This is going to be critically important information about Aria’s mechanism of disease which should open doors to more treatment options for her. Your donation will be making a difference.

Stage 4. Mouse Model

The University of Modena and Reggio Emillia in Italy is helping Aria by creating a mouse model and further expanding their expertise on the LONP1 mutation. (With some luck, this is being separately funded by the Italian Foundation Telethon, all being well )

Aria is the sole example of her mutation in the LONP1 gene, so exploring her genetics is of clinical significance to many researchers. We are most grateful to Prof Marcello Pinti who is one of the world’s leading researcher with multiple papers on LONP1. Prof Marcello Pinti is looking to raise funds directly inside of Italy to fund this separate phase of work.

Stage 5. Access the best medical clinicians for Mitochondrial disease.

There are many Mito centres in Children’s Hospitals around the world. We are currently exploring which centres would offer Aria the best possible care.

To enroll in healthcare outside of Aria’s home country the UK will be expensive. So we are most grateful for your donations, this all goes to give Aria access to clinical medical care in the best global centres. Currently, we are exploring centres in the USA and Italy.