The Cure ADOA Foundation is very pleased that drug manufacturer PYC is allowed to trial a groundbreaking drug against ADOA. Board member Hedy Smit-Wigchers responded hopefully and enthusiastically when she received an email about this from Rohan Hockings, the CEO of PYC. “This is absolutely great news! It is the first drug ever developed specifically for ADOA and is now being tested in a patient for the first time.”
PYC has received approval from the Human Research Ethics Committee (HREC) in Australia to initiate clinical trials of an RNA therapy specifically developed for patients with Autosomal Dominant Optic Atrophy (ADOA). This means that the first patients will receive the medicine this quarter. The study is necessary to discover the improvements in visual function and functional vision of the patients. In addition, any possible side effects of the medicine are recorded.
Getting approval for a clinical trial is a process that takes a lot of time. PYC has now met all requirements to test the drug PYC-001 on humans. A small group of patients receive the drug via an intravitreal injection. This means that it is injected into the vitreous body of the eye through a very thin injection needle.
The medication for ADOA is the second RNA therapy that PYC is working on. The first therapy is aimed at retinitis pigmentosa type 11. One of the major challenges with RNA therapy is ensuring that the drug reaches exactly where it is needed in the cell. For the retinitis pigmentosa drug, PYC had already developed a unique RNA therapy in which the RNA is delivered by peptides. This works better than the traditional way with viruses. Other things that the researchers have learned thanks to the retinitis pigmentosa program can also be applied in the program for ADOA.
How it works
ADOA is caused by a genetic mutation of the OPA1 gene, which makes the OPA1 protein. OPA1 is necessary for the mitochondria, which make energy molecules (ATP) in the cells. A decrease in the OPA1 protein leads to vision loss because the retinal ganglion cells, which transmit the signal from the eye to the brain, require a lot of energy. With a reduced OPA1 molecule, the structure of the mitochondria responsible for ATP production changes. It becomes less stable and actually falls apart. As a result, the mitochondria cannot produce enough ATP. If the mitochondria cannot produce enough energy, the cell is less able to resist stress and other challenges, and eventually the cell dies.
PYC attempts to increase the amount of OPA1 protein the cell makes to achieve the correct balance of the OPA1 molecule. When this is successful, the entire chain of events leading to vision loss is addressed.
To stop ADOA, PYC is developing an RNA therapy. RNA is a biological macromolecule that regulates cellular processes. It is made by DNA and itself makes the protein for the cells. RNA therapy has advantages over gene therapy in the case of ADOA. Changes at the DNA level are permanent, while tuning gene expression at the RNA level is not permanent. If damage occurs as a result of the therapy, it is therefore reversible. In addition, the dosage per patient can be determined more accurately.
