Table of contents:
• Why are we working on Wilson Disease
• How artificial intelligence helps us discover therapies
• Deep Genomics takes on Wilson Disease
• Helping prepare the Wilson Disease community for the development of genetic medicines

Deep Genomics is a biotechnology company that builds proprietary artificial intelligence (AI) technology and uses it to discover new ways to correct the effects of genetic mutations and develop personalized therapies for individuals with rare disease.

In 1995, our founder Dr. Brendan Frey helped to lay the foundation for the highly successful artificial intelligence technology called “deep learning”. That’s the technology that’s changing everything, from farmers growing better crops to cell phones converting speech to text. In 2002, he faced a family medical crisis that led him to recognize that good drugs are based on good biology, but biology is too complex for humans to understand and accurately predict, especially at scale. So, Dr. Frey decided to focus on that problem. For the next 13 years, he and his team built artificial intelligence that could be used to successfully discover the genetic causes of disease and new therapeutic approaches to treat them. Their discoveries made the front pages of journals like Nature Magazine, and international newspapers, such as the New York Times.

By 2015, the artificial intelligence technology was so powerful that it was time to bring it to patients. The team founded Deep Genomics, whose mission is to serve patients by building and using artificial intelligence to discover and develop better treatments for rare genetic diseases.

In 2018 this artificial intelligence technology discovered how a specific Wilson Disease-causing mutation works, something human scientist hadn’t yet figured out (you can read our paper on that discovery here). Recognizing the unmet need in Wilson Disease and armed with this insight Deep Genomics launched the world’s first AI directed therapeutics program for Wilson Disease.

We have prepared a short video summarizing how Deep Genomics uses artificial intelligence to discover potential therapies that target these genetic diseases.

Genetics

To understand how we use artificial intelligence to design potential therapies, let’s first review some basic concepts in genetics.

Our genes are made of DNA which is present in nearly every cell of our bodies. Each gene is usually present in two copies, one from each parent. The DNA provides the instructions to make different proteins which are responsible for the various functions in the body. For example, proteins are important for hair and eye color, growth, brain development, movement and metabolism - the conversion of food into energy or body fat and muscle.

The process of building proteins begins with DNA. Cells first read the instructions contained in DNA, which are written using the genetic alphabet of A, C, G and T, to make a copy called RNA, which is written using a similar genetic alphabet. This process is called transcription. Then, cells read the instructions contained in the RNA to make proteins, using a process called translation. You can think of RNA as the molecule that carries the message between the DNA and the protein.

Many rare diseases are caused by changes to the letters in the DNA, called genetic mutations. Mutations in the DNA get transferred to the RNA and this can lead to a protein that doesn’t work properly, or can even prevent a protein from being made at all. Many rare genetic diseases are caused by these types of mutations.

Deep Genomics uses artificial intelligence to discover potential therapies that target these genetic diseases.

For a single rare disease, there may be thousands of disease-causing mutations to look at, and hundreds of different ways of trying to fix the problem. On top of that, there may be hundreds of thousands to millions of potential drugs to search through, but only a few that work.

Sifting through so many possibilities to find those that may help is incredibly time consuming, and complicated, for human scientists, and that’s where our artificial intelligence technology offers advantages.

There are two main ways we use our artificial intelligence to help us develop potential medicines.

1. Using artificial intelligence to discover targets

First, we use artificial intelligence to rapidly examine all the possibilities and identify disease-causing mutations and ways of fixing the genetic problem. This is called target discovery and because there may be thousands of mutations and hundreds of different ways to fix the problem, having a computer do the work is a big boost.

2. Using artificial intelligence to design therapies

Second, we use artificial intelligence to design therapeutic candidates. For a specific disease, our artificial intelligence can assess hundreds of thousands to millions of different potential targeted therapies to find the ones that are most likely the best. These are then verified in our lab. Again, a big boost.

The class of therapies that Deep Genomics is currently developing are called steric-blocking oligonucleotides.

Steric blocking oligonucleotides

Steric blocking oligonucleotides are short stretches of special DNA or RNA that attach to a specific place in the RNA. By doing so, they modify that natural way in which cells process the RNA and build proteins. They don’t make any permanent changes to the DNA.

A steric blocking oligonucleotide can potentially restore production or the amount of the protein.

Wilson Disease is a genetic condition, which results from excessive copper in the body. Wilson Disease is caused by mutations in the ATP7B gene and more than 300 disease-causing mutations have been identified. The condition is inherited in an autosomal recessive pattern, which means individuals with Wilson Disease have disease-causing mutations in both copies of their ATP7B gene. There are three main features of Wilson Disease: liver disease, neurological decline, and neuropsychiatric symptoms. Many patients have deposits of copper in the eye, called Kayser-Fleischer rings.

For additional information please visit the National Organization for Rare Disorders’ page on Wilson Disease: https://rarediseases.org/rare-diseases/wilson-disease/

Currently, there are no approved treatments available that restore ATP7B protein levels or function and address neurological symptoms. Deep Genomics is working to identify therapies that can potentially restore ATP7B protein levels and function and advance them into the clinic. These therapies may address 40% or more of patients with Wilson Disease and are aimed at potentially improving neurological symptoms as well as liver function.

Gout

Gout is a disorder caused by excessive urate production and/or insufficient urate elimination in the urine, which result in urate crystal deposition in the joints and inflammatory arthritis. In North America, gout is present in about 3% of the population. Arthritis symptoms can be treated by anti-inflammatory drugs, and urate levels can be modulated using urate synthesis inhibitors and enhancers of urate excretion. However, about 150,000 patients have treatment-refractory gout, which means that available pharmacological treatment has failed to normalize their urate levels and they have persistent joint pain. Deep Genomics is working to identify therapies that can potentially more effectively suppress urate synthesis.

Niemann-Pick Disease Type C

Niemann-Pick Disease Type C (NPC) is a severe and often fatal neurodegenerative disorder characterized by ataxia (lack of voluntary coordination of muscle movements), cognitive impairment and dementia. Its prevalence is reported as 1.1 / 100,000 in individuals of European descent. NPC is caused by recessive pathogenic variants in the gene ‘NPC intracellular cholesterol transporter 1’ (NPC1). Loss of NPC1 function results in cholesterol accumulation in neurons, leading to their dysfunction and death. Based on age of onset and severity, five NPC forms have been recognized: fatal systemic perinatal, early infantile, late infantile, juvenile and adolescent / adult. For additional information please visit the National Organization for Rare Disorders’ page on Niemann-Pick Disease Type C: https://rarediseases.org/rare-diseases/niemann-pick-disease-type-c /

Currently, there are no approved treatments available that restore NPC1 protein levels or function. Deep Genomics is working to identify therapies that can potentially restore NPC1 protein levels and function and advance them into the clinic.

Frontotemporal Dementia Caused by Granulin Precursor

Frontotemporal Dementia (FTD) is a fatal neurodegenerative disorder characterized by rapidly progressing deficits in executive function and language, accompanied by behavioral and personality changes. It can be caused by dominant pathogenic variants in the gene Granulin Precursor (GRN), with an estimated prevalence of 7.5-9 / 1 M in individuals of European descent. Partial loss of GRN function leads to neuron degeneration and death, primarily impacting the frontal and temporal lobes of the cerebral cortex. For additional information please visit the National Organization for Rare Disorders’ page on Frontotemporal Dementia: https://rarediseases.org/rare-diseases/frontotemporal-degeneration /

Currently, there are no approved treatments available that restore GRN protein levels or function. Deep Genomics is working to identify therapies that can potentially restore GRN protein levels and function and advance them into the clinic.

Deep Genomics has partnered with the Wilson Disease Association and with physicians, around the world, to help ensure that we consider the needs of Wilson Disease patients. Two examples of that are below:

Free genetic testing

To help patients confirm their diagnoses and understand their disease-causing mutations, Deep Genomics has partnered with a well respected clinical lab, PreventionGenetics, to offer free genetic testing for Wilson Disease patients. If you are interested in pursuing testing, you can direct your doctor to visit the PreventionGenetics, website for additional information.

https://www.preventiongenetics.com/sponsoredTesting/DeepGenomics

Providing support with medical records

To help us and other researchers better understand the disease and how to treat it, you may wish to participate in a large study of clinical records. Deep Genomics has partnered with AllStripes (formerly known as RDMD) to give patients access to their own medical records and to help researchers use the data to study new treatments. If you are interested in learning more about this study, you can visit the AllStripes website.

https://www.allstripes.com/wilson 

For additional information or questions, contact wilsondisease@deepgenomics.com.

Sponsored testing and AllStripes patient materials:

PreventionGenetics.pdf

AllStripes.pdf