AdventHealth for Children Collaborating with n-Lorem Foundation to Provide Personalized Treatments to Patients with Nano-rare Genetic Diseases

The n-Lorem Foundation recently selected AdventHealth for Children in Orlando as one of the first institutions in Florida to collaborate with providing personalized antisense oligonucleotide (ASO) medicines discovered and developed at n-Lorem to three children with extremely rare genetic diseases, also called nano-rare disorders. Each of these children has a unique and extremely rare genetic condition that necessitates an individualized ASO designed only for that patient. Board-certified clinical and biochemical geneticist and cytogeneticist Majed Dasouki, MD, who serves as medical director of genomics and personalized health at AdventHealth for Children, submitted the patient applications to n-Lorem and will work as the investigator and treating physician for these research efforts.

Understanding Nano-rare Conditions

Nano-rare means a patient’s genetic mutation is only found in 1–30 patients in the world. These patients typically have a single gene mutation that causes symptoms that negatively impact their health. In many cases, the mutation leads to degenerative conditions or death.

“Patients with rare genetic disorders have long been underserved,” shares Dr. Dasouki. “These conditions are life-threating or life-limiting, but because they are so rare, the commercial model for therapy development is cost prohibitive and simply doesn’t work. As a result, we’ve historically only been able to treat these patients’ symptoms rather than the root cause of their disease, and these palliative therapies often cause significant negative side effects that affect the quality of life for the patients and may lose efficacy over time. In fact, many patients with nano-rare genetic diseases have already exhausted all therapeutic measures and have no effective treatment options left.”

ASO Treatment Technology and the n-Lorem Foundation

A non-profit foundation based in California, n-Lorem discovers, develops and provides individual treatments for pediatric and adult patients with nano-rare diseases for free, and they guarantee free drug for the life of the patient.

“n-Lorem utilizes a well understood, efficient and cost-effective technology – ASO technology – to bring these personalized medicines to its patients,” says Dr. Dasouki.

ASOs are short strands of modified DNA that can specifically target the transcripts of a defective gene, binding precisely with the gene’s RNA to modify the process that is causing the disease.

“Though the discovery and development of ASOs may sound simple, it is not,” explains Dr. Dasouki. “It requires significant expertise, knowledge, experience and automation that n-Lorem has. Not only is it important that only an optimized ASO be developed, careful consideration of dosing parameters is also vitally important. The n-Lorem/AdventHealth team will work closely together to ensure that each patient is professionally managed throughout treatment.”

The n-Lorem Foundation only develops ASO treatments for organs where they have the most experience and can achieve the best potency, which currently includes the liver, kidney, eye and central nervous system. Experimental ASO medicines can be administered subcutaneously, intravitreally or intrathecally depending on the most effective approach for the target organ.

“The beauty of an ASO medicine is that it is highly specific to a patient’s unique genetic mutation, addresses the root cause of their disease and can be developed rapidly thanks to n-Lorem’s technology and innovative non-profit model,” comments Dr. Dasouki. “Additionally, thanks to n-Lorem’s generous investors and partners, they provide these treatments to nano-rare patients at no charge.”

A Collaborative Approach to Developing a Customized Treatment

Discovering, developing and providing personalized experimental ASO medicine to nano-rare patients is a collaborative effort. To be a candidate for treatment through n-Lorem, a patient must have a nano-rare diagnosis, the genetic cause must be defined through a full genomic analysis, and the patient must be cared for by an investigator physician at a tertiary care institution experienced in managing investigational new drugs (INDs).

Dr. Dasouki and the genomics team at AdventHealth for Children had identified three children who met n-Lorem’s qualifications, performed comprehensive genomic analyses on each patient using biopsied skin cells and submitted separate applications for each patient to n-Lorem. n-Lorem then leads and oversees the entire design, discovery and development process to identify the most optimal ASO to move forward in development. They evaluate tolerability and potential toxicity of each ASO medicine candidate using the preclinical guidance issued by the U.S. Food and Drug Administration (FDA). All this work will be submitted to a local institutional review board (IRB) and eventually, the FDA for permission to proceed with treatment before the first dose is administered to the patient.

“We are thrilled to have been selected for this innovative opportunity to work with n-Lorem to bring innovative, personalized medicine to nano-rare patients,” shares Dr. Dasouki. “Our goal for this collaboration is to develop highly personalized protocols for our nano-rare patients whenever feasible -- a single effective drug for a single patient for a single treatment period. Ultimately, we believe this approach will provide our patients with new hope and the opportunity to live better, healthier, more whole lives.”