Alzheimer’s disease preclinical detection is key to early treatment approaches. New eye test is DARC. Detection of Apoptosing Retinal Cells finds dying nerve cells in eye retina. Eye develops from a brain. Retina is affected by neurodegeneration. Curcumin (turmeric) fluoresces when it binds beta amyloid. Amyloid deposits in retina and brain in Alzheimer’s disease.
Retinal nerve cells could be dying in the eye for many years. Dr. Anton Titov, MD. It happens before nerve cells will start dying in the brain. This could signify an onset of clinical Alzheimer's disease. Dr. Francesca Cordeiro, MD. Yes, absolutely, that is the hypothesis. But there is other research that has been going on again. We are looking into this as well. Sometimes you can look for the beta amyloid in plaques being deposited in the retina. You do see that in the transgenic Alzheimer models. These are experimental mouse models. Glaucoma and Alzheimer’s disease have the retina affected. Patients do have beta amyloid abnormally deposited in the retina. You can observe beta amyloid in the retina with some florescent markers. We know the turmeric binds beta amyloid. Turmeric is the orange spice that is used a lot in curries. When turmeric binds beta amyloid protein, it fluoresces. So, in the retina you can pick up the fluorescence. It is a marker of beta amyloid protein being deposited in the retina. There is more data that suggests the meaning of these retinal changes. It could highlight death of neurons in the retina before they may even happen in the brain. But these findings need to be really assessed properly in large scale population clinical trials. But potentially this eye test for Alzheimer’s disease could be an outpatient test. Dr. Anton Titov, MD. You can do this diagnostic test with the equipment that exists at ophthalmologists and optometrists. You just inject the dye under proper conditions. Dr. Francesca Cordeiro, MD. We developed an eye drop. So a physician is able to do this in outpatient clinic. Doing the eye drops and standard scan can potentially identify patients who are at higher risk for Alzheimer’s disease. Dr. Anton Titov, MD. This can select patients with Alzheimer’s disease for early treatment. Yes. But perhaps another, more imaginable early benefit of this would be using this "Alzheimer's eye test”. It is to assess response to treatment of Alzheimer’s disease. It is very difficult for Alzheimer's disease treatment to know how a patient is responding to therapy. Potential test to diagnose a preclinical stage of Alzheimer's disease. Diagnostic test is looking how the cells die in the retina. That is the test that is undergoing clinical investigations now. But one of the biggest problems in Alzheimer's disease clinical trials is that. It takes a long time to determine whether a medication candidate works or it doesn’t. Because of the very subtle changes in Alzheimer’s disease. The test that you developed can potentially revolutionize the diagnosis of Alzheimer’s disease. It can also compress the time frame of the clinical trials of Alzheimer’s disease therapy. Dr. Anton Titov, MD. Could you please talk about the significance of your test for Alzheimer’s disease? Dr. Francesca Cordeiro, MD. This diagnostic test is not just for the clinical practice that we just discussed. But it is also for the medication clinical trials in Alzheimer's disease. Yes. We have published test results in Parkinson's disease model as well. What we are suggesting is that. You can use the level of apoptosis where you see these fluorescent spots in the retina as a measure of Parkinson’s disease activity. Sometimes you successfully treat your patient, then this Parkinson’s disease activity should go down. The number of cells with apoptosis in retina should go down. We have shown this in a number of eye disease models. But experimental model for Parkinson's eye disease definitely has suggested this. You can use this as an indicator of whether your Parkinson’s disease treatment is successful. You see treatment result much earlier than you can see changes in the brain. In this particular study with the Parkinson's model we show this. The retinal apoptosis have gone down well before brain changes. There were changes that have been reversed in the brain regarding substantia nigra. It is brain area affected in Parkinson’s disease. Dr. Anton Titov, MD. That is important because this retinal diagnostic test is a relatively non-invasive test. It's easy to do as you've seen yourself. This eye diagnostic test can be done in an outpatient department. It means that you can use this diagnostic test as a way of determining the response to Parkinson’s disease treatment at all. In all these diseases we suggest to start with a baseline level of activity. So, you see some number of cells. Dr. Francesca Cordeiro, MD. We are talking about 20, maybe 30 retinal cells with apoptosis. These retinal cells are dying. This is a sign of neurodegeneration. You get your patient with Alzheimer’s disease on a good treatment. Therapy works well. Maybe the number of dying cells in the retina will go down. We don't know the absolute numbers at the moment. We are expecting a number of retinal cells that show signs of apoptosis to be much higher when you look all the way around the eye. But the importance of diagnostic test for Alzheimer’s disease is just a decline in the number of these dying retinal cells. It will be a good enough indicator that you have your patient on the correct treatment.