It all began with an email in 2019. Matt Might, director of the Hugh Kaul Precision Medicine Institute, shot his thoughts over to neurosurgery resident Matt Davis, whose 3-year-old son has ADNP Syndrome. The email contained only two brief lines:
It looks like low-dose ketamine is an up-regulator for ADNP. Do you think this makes sense for ADNP patients?
Davis’ experience with his son, as well as his role in medicine, inspired him to connect with Sandra Bedrosian-Sermone, the founder of the ADNP Kids Research Foundation. He joined their medical advisory board so that the organization can continue making strides in ADNP syndrome research. Now, this rare disease patient organization and other researchers are using tools like artificial intelligence to change the way we view this condition.
Read the full story of their journey and achievements on the ADNP Kids Research Foundation website.
ADNP Syndrome
This rare neuro-developmental disorder impacts neuronal and bodily function. It is caused by a mutated ADNP gene, which stands for Activity Dependent Neuroprotective Protein. Most children with ADNP syndrome have one normal ADNP copy and one mutated one.
Elements of ADNP syndrome include:
- Impaired communication ability,
- Intellectual disabilities,
- Global motor planning disorders,
- Autism,
- Anxiety, ADHD, or OCD,
- Problems with sleep,
- An inability to talk (which only occurs in some patients),
- Weak muscle tone,
- Digestive issues,
- Vision issues, and
- Prominent facial features such as drooping eyeliner, a high hairline, and a thin upper lip.
Only 250 children worldwide have been diagnosed with ADNP syndrome. Read more here.
Using Artificial Intelligence in the Medical Realm
Both Matt Davis and Matt Might are well-versed in rare conditions, and work together at the University of Alabama – Birmingham. In fact, Might’s son was the first ever patient diagnosed with a rare genetic condition called NGLY1 deficiency.
Normally, NGLY1 creates the N-glycanase enzyme that clears damaged or broken proteins from the body. The genetic mutation prevents the body from breaking down or removing these broken proteins, causing them to accumulate. Symptoms include intellectual disabilities, seizures, an inability to produce tears, developmental issues, liver disease, low muscle tone, tremors, and skeletal defects. Learn more about NGLY1 deficiency from NORD.
During the journey to diagnosis, Might, a computer scientist, wanted to understand how to help his son thrive. He rigorously researched genetics and targeted drug therapies. Then, at the Precision Medicine Institute, he developed mediKanren.
This artificial intelligence tool uses data pulled from medical literature and other resources to determine information, and potential cures, for rare conditions.
Ketamine, ADNP Syndrome, and Clinic Trials
Last year, Sermone, the founder of ADNPkids and the ADNP Kids Research Foundation (501©3 2016), teamed up with Davis, a neurosurgeon at the University of Alabama – Birmingham. Both being parents of children with ADNP syndrome, the two collaborated to find treatments for the condition.
First, the pair began looking into repurposed drug development. It was around this time that Davis and Might also connected. They came up with an idea: providing Might’s AI tool, mediKanren, with data and information on ADNP syndrome. After percolating, the AI tool came back with several therapeutic options, including ketamine. It was this that really stuck out to Sermone and Davis. Soon, ketamine became the focus of their studies.
Ketamine
Currently, ketamine is a Schedule III controlled substance. It was initially designed as an anesthetic, and later approved for human use in the 1970’s. Ketamine does have addictive qualities. However, in lower doses, it can be effective for the treatment of:
- Pain
- Depression and anxiety
- Asthma
- Seizures
The Journey to Clinical Trials
As a doctor, Davis gained access to helpful data from medical publications. He also spoke to other doctors and scientists. Simultaneously, Sermone was independently researching ketamine, attending drug development and biotechnology conferences, and building a foundation of knowledge to further their cause. Together, the two created a clear and succinct case for testing low-dose ketamine as a potential treatment for ADNP syndrome.
Their next step? Pitching their findings. Sermone presented their data to Dr. Joseph D. Buxbaum at Mount Sinai. From there, Buxbaum and his team (headed by Dr. Alex Kolevzon), who focus on genetics and genomic sciences, submitted the study to the Food and Drug Administration.
In January of 2020, the application was approved. Now, the team is running the first ever drug trial related to ADNP syndrome. In fact, as of May 19, the trial has officially begun!
Might, for one, is extremely impressed. While he always aims to guide and empower patient organizations, he notes that Sermone and Davis were able to quickly and effectively get their work to trial.
But Sermone also credits his help, noting:
“This model of patient-involved research is crucial to driving breakthroughs in science for rare disease. It’s up to us to try to do everything that we can and push like hell for drug discovery because no one else is going to care more about our children than we are. If it wasn’t for fellow rare disease dad Matt Might looking into AI for ADNP, we would not have had any idea to look up ketamine.”
Moving forward, Might, Davis, and Bedrosian-Sermone hope three things. First, they hope that artificial intelligence can continue to discover new treatment options for rare conditions. Next, they hope to source additional funding for future their Ketamine clinical trial. Finally, the three hope that this will usher in a new era of treatment and change for patients and their families.
Learn more about the ADNP Kids Research Foundation and their mission.
