The PATrOL™ Platform
Every human being is unique at the genetic level (even identical twins by the way). Each of us carries a six billion letter genetic sequence or “genome”. We get one three billion letter copy from our mother and one copy from our father, and together they form the blueprint for how our bodies function.
There are differences in the DNA sequence between people across a population, and these variations give rise to all the wonderful nuances that make each of us special and interesting. Sometimes changes in a DNA sequence cause a downstream biological process to go awry, resulting in a genetic disorder. In this case, the DNA variation is termed a “mutation” (a technical term that simply describes the difference between a change at a position that causes differences between people and one that causes a disorder). DNA in each cell of the body is copied into RNA, which then serves as a template for producing a protein. Proteins do most of the work in the cell. When errors in a DNA sequence occur, they are transferred to RNA and can become a damaging protein, resulting in a disorder.
Our Peptide-nucleic acid AnTisense OLigonucleotide (PATrOL™) platform is a new plug-and-play approach that allows us to design and develop drugs that tightly bind to the incorrectly spelled or “mutant” RNA and prevent it from ever becoming a damaging protein. PATrOL™-enabled therapies can reach organs throughout the entire body and are envisioned to be delivered through a simple infusion, removing the need for complex and invasive surgeries common to similar approaches.
Using the PATrOL™ platform, we are developing new treatments for a range of genetic disorders that have the potential to alleviate symptoms and even slow or stop disease progression. Learn more about the science behind PATrOL™ and its potential to treat genetic diseases here.
Huntington’s disease (HD) is a rare genetic disease caused by a mutation in the huntingtin (HTT) gene, which is thought to be important for many essential cell activities. Those with HD experience a loss of neurons in the brain over time mostly due to the toxic accumulation of faulty HTT protein in their cells. Current treatment options work to lessen individual movement and psychiatric symptoms, but there is no treatment for HD that can slow or stop the progression of the disease.
Juvenile Huntington’s disease (JHD) occurs when someone who is 20 years old or younger begins to develop symptoms of the disease. Patients with JHD experience similar symptoms to those with adult-onset HD, however, the progression of the disease is typically much more rapid. In addition, individuals with JHD can suffer from gastrointestinal problems, burning or itching skin and sometimes seizures. JHD is often miss-diagnosed as autism spectrum disorder. Approximately 10-15% of all HD is JHD, and yet only about 1/10th of the individuals who suffer from JHD receive a diagnosis.
Using our PATrOL™ platform, we are developing NT0100 to potentially slow the progression of both HD and JHD by eliminating the production of faulty HTT protein while allowing the production of healthy HTT protein. NT0100 is designed to be administered into the bloodstream rather than directly into the spine, hopefully allowing for a more convenient and less invasive treatment option than others currently being developed.
If you or a loved one has recently been diagnosed with HD or JHD, you can find some additional resources below. For young people in the HD community looking for resources and support services, including patients with the juvenile form of HD, pre-manifest patients and children of those affected by the disease, please visit the Huntington’s Disease Youth Organization (HDYO). The HDYO is dedicated to supporting those under 35 who are impacted by the disease.
Myotonic dystrophy type 1 (DM1) is a rare genetic disorder caused by a mutation in the DMPK gene, which is important for the correct functioning of skeletal muscles, the heart and the brain. Current treatment options include therapies to manage the symptoms, physical therapy for muscle weakness, swallowing and pronunciation issues and assistive devices such as braces or crutches to help with mobility. No treatments currently exist that slow or stop the progression of DM1.
Individuals who have a mutation on one copy of their DMPK gene actually have more genetic material than individuals without the mutation! The additional genetic information is in the form what is called a “trinucleotide repeat”, or a series of three letters which is repeated often hundreds or thousands of times on that copy of the gene. While more might seem better, this extra genetic material forms into a structure that looks like a hairpin. This unusual hairpin acts like a magnet to attract a protein in the nucleus of the cell and forms an aggregate. These aggregates can actually be seen with a microscope in individuals with DM1, and result in cells not being able to function correctly.
Using our PATrOL™ platform, NeuBase is currently developing NT0200 as a new treatment option for DM1. NT0200 is intended to seek out and engage with the hairpin on just the mutant copy of the DMPK RNA molecule and displace the protein aggregate to restore normal cellular function in individuals with DM1, potentially stopping or slowing disease progression. Importantly (and different from others working to develop similar therapies), our solution does not hamper production of normal DMPK protein in individuals with DM1.
If you or a loved one has recently been diagnosed with DM1, you can find some additional resources below.