You Can Teach an Old Drug New Tricks

Previously Approved Drug Shows Promise for Dry Age-Related Macular Degeneration (AMD)

Getting FDA approval for new treatments can take years or even decades. But what about repurposing drugs that have already been approved for other diseases? That’s precisely the question DEF-supported researchers are asking about a new treatment for dry age-related macular degeneration (AMD) and other aging diseases, including Alzheimer’s and Parkinson’s.

Six years ago, DEF Research Director Dr. Cristina Kenney began collaborating with Parkinson’s specialist Dr. Howard Federoff of the Department of Neurology at UC Irvine. DEF-supported researchers had previously shown that damaged mitochondria are a significant factor in accelerating cell death in AMD, and Kenney developed a cybrid mitochondria model to study AMD. Federoff had set up a screening system to look at drugs previously approved by the FDA that might improve the health of mitochondria, whose demise also contribute to Parkinson’s and Alzheimer’s. Of more than a thousand drugs screened, he identified 13 that could rejuvenate mitochondria. Kenney’s cell-culture models and Federoff’s system were a match made in research heaven.

Together, the researchers homed in on one drug, which Federoff named PU-91, because it was the 91st drug he’d tested. “When we added PU-91 to our AMD cybrids, the cells lived longer, they functioned better the damage to the mitochondria was decreased and it really improved the health of the mitochondria,” Kenney says. “PU-91 is a drug called fenofibrate, which has been used for years to treat high cholesterol. When this drug is modified slightly, it helps sluggish mitochondria regain their health. We’re taking a drug that has been used for many years with FDA approval, and we’re repurposing it for a new target and new types of diseases.”

Benefits of Repurposing

Tremendous savings of time and money are to be had by repurposing a known drug rather than starting with a drug people have never used before. Perhaps most importantly, because it’s been used for so many years in patients, the known drug has a proven safety track record. PU-91 has an additional advantage in that it is taken orally. While there is currently one type of treatment for wet AMD — an injection — there is no treatment at all for the dry form of AMD. An oral treatment for dry AMD is a game-changer.

The research is going so well that a company has been formed specifically to bring this drug to market for dry AMD. “As we become more successful, this type of drug can also be used for neurodegenerative diseases that have damaged mitochondria, such as Parkinson’s disease and Alzheimer’s disease,” Kenney says. “Potentially, it might even be used for something, such as glaucoma, that causes cell death of the retina ganglion cells in the eye. There are a lot of potential uses for it.”

Bench to Bedside

DEF currently is supporting ongoing studies to optimize PU-91’s formulations for maximum effectiveness in patients with AMD. “It’s exciting, because this is the goal for translational researchers,” Kenney says. “Take what you’re doing at the bench and bring it to the bedside.”

If you would like to support our sight saving research click here, DONATE NOW

Beauty is in the Eyes of the Beholder

I love the idea that beauty is in the eyes of the beholder. It reminds us that individuals can make choices about what they perceive to be true beauty.

Let’s consider art… one person’s beautiful can be another person’s junk. If beauty is in the eyes of the beholder, the question is – are we taking the time to appreciate all that surrounds us? From Mother Nature’s unlimited panoplies of possibilities to the innocent smile of a child, beauty is the catalyst that makes being alive the greatest of all human adventures.

I am sure you’ve heard the phrase “stop and smell the roses,” so why not take the time to stop and observe the beauty your eyes can behold.

The Discovery Eye Foundation is working every day to preserve your vision and give all of us the chance to see what’s truly beautiful and treasure it. All you have to do is open your eyes and take a look.

Louis Armstrong said it well:

I see trees of green and red roses too.
I see them bloom for me and you.
And I think to myself,
what a wonderful world.

You’re right Louis… it is a wonderful world if we all just keep appreciating the beauty that’s out there for all of us.

Donate today to help support the Discovery Eye Foundation!

Tom Sullivan
DEF’s Ambassador of Vision
sullivanvision.com

Coronavirus and Your Eyes: What you should know

Coronavirus (COVID-19) can cause mild to severe respiratory illness. Symptoms such as fever, cough, shortness of breath and pink eye can show up 2 to 14 days after a person is exposed. People with severe infections can develop pneumonia and even die from complications of the illness.

To cut your personal risk of contracting the COVID-19, avoid touching your eyes, nose, mouth and face with unwashed hands. It is the mucous membranes (membranes that line various cavities in the body) that are most susceptible to transmission of the virus.

To avoid infecting others with the coronavirus, the Centers for Disease Control and Prevention (CDC) has recommended the use of face masks to be worn when out in public. Face masks can reduce the spread of coronavirus by people who are infected but have no symptoms of the virus (asymptomatic). Face masks, however, do not protect your eyes from infection.

Here are a few tips on how to protect yourself and others:

1. Practice safe hygiene and social distancing — The Centers for Disease Control and Prevention (CDC) offer these general guidelines to slow the spread of disease:

Wash your hands often with soap and hot water for at least 20 seconds. (Singing Happy Birthday twice is about 20 seconds)
You should especially wash your hands before eating, after using the restroom, sneezing, coughing or blowing your nose.
If you can’t get to a sink, use a hand sanitizer that has at least 60% alcohol.
Avoid touching your face — particularly your eyes, nose, and mouth.
If you cough or sneeze, cover your face with your elbow or a tissue. If you use a tissue, throw it away promptly. Then go wash your hands.
Avoid close contact with sick people. If you think someone has a respiratory infection, it’s safest to stay 6 feet away.
Stay home when you are sick.
Regularly disinfect commonly touched surfaces and items in your house, such as doorknobs, refrigerator door handles and counter tops.

2. Coronavirus may cause pink eye, so avoid touching eye discharge — Someone may have pink eye but it doesn’t mean that person is infected with coronavirus. But a recent study suggests that up to one third of people hospitalized with coronavirus experience eye problems, such as viral pink eye or conjunctivitis. It’s important to know that the virus can spread by touching fluid from an infected person’s eyes, or from objects that carry the fluid.

3. Avoid rubbing your eyes — We all tend to do it and natural habits can be hard to break but doing so will lower your risk of infection. Use a tissue instead of your fingers when you feel the urge to rub your eye or even to adjust your glasses. Dry eyes can lead to more rubbing, so consider adding moisturizing drops to your eye routine. If you must touch your eyes for any reason wash your hands first with soap and water for at least 20 seconds. Then wash them again afterwards.

4. If you wear contact lenses, consider switching to glasses for a while — There’s no evidence that wearing contact lenses increases your risk of coronavirus infection although contact lens wearers touch their eyes more than the average person. Substituting glasses for contacts can decrease irritation and will lower the chances of you touching your eye. If you choose to continue wearing contact lenses, follow these hygiene tips.

5. Make sure you are well supplied on eye medicine prescriptions if you can — During this pandemic experts have advised patients to stock up on critical medications, enough to get by if you are quarantined or if supplies become limited. If your insurance allows you to get more than 1 month of essential eye medicine, such as glaucoma drops, you should do so. Some insurers will approve a 3-month supply of medication in times of natural disaster. Ask your pharmacist or ophthalmologist for help if you have trouble getting approval from your insurance company. Don’t wait until the last minute to contact your pharmacy, request a refill as soon as you’re due.

IF YOU’RE NOT FEELING WELL – Call your family doctor. If you suspect you may have pink eye (conjunctivitis), call an eye doctor near you. It is suggested that patients not go directly to medical or eye care facilities without a prior phone call to help to decrease the possible spread of the virus. A phone call allows the health facility to prepare for your visit and diagnose and treat you in a proper manner.
You may feel nervous about going to the doctor’s office during this pandemic. But treatment for eye emergencies should not be delayed. Ophthalmologists, like all medical professionals, follow strict hygiene and disinfection guidelines.

Ophthalmologists are available to treat urgent eye issues, deliver eye injections and provide critical care. Call your ophthalmologist or other medical doctor as soon as possible in the following situations:

You have macular degeneration or diabetic retinopathy and get regular eye injections.
You notice changes in your vision (like blurry, wavy or blank spots in your field of vision).
You experience an eye injury, even if it seems minor.
You suddenly lose some vision.
You have eye pain, headache, red eye, nausea and vomiting.

Protect yourself and the eye care team by following these precautions:

Wear a mask to a medical appointment. The mask should cover your nose and mouth.
If you have a cough or a fever, or have been in close contact with someone who has these symptoms, you must call your doctor’s office ahead of time and let them know. After you speak with the health care profession, it may be decided that your visit is not an emergency, and you can be treated at home. If you arrive sick at the doctor’s office, you should wear a protective covering or mask, and they may want you to wait in a special room away from other patients.
If you need to cough or sneeze during your exam, move back from the microscope. Bury your face in the crook of your arm or cover your face with a tissue. Wash your hands with soap and water right away.

For more Coronavirus information visit: www.cdc.gov/coronavirus

For more information about the Discovery Eye Foundations new research for Coronavirus vaccine visit: www.discoveryeye.org/covid-19-emergency-research/

COVID-19 EMERGENCY RESEARCH

A MESSAGE FROM ANTHONY B. NESBURN, DEF PRESIDENT & MEDICAL DIRECTOR

The world is being held hostage by coronavirus (COVID-19). The number of cases and deaths are climbing everyday. Scientists and pharmaceutical companies are working feverishly to create a vaccine, but it is at least a year away. There is also hope that existing FDA-approved drugs, such as hydroxychloroquine and azithromycin, may be able to ameliorate the disease and prevent deaths. These need to be tested now—see below.

During this emergency, DEF Research Director Dr. Cristina Kenney’s laboratory is applying the knowledge gained from her work on age-related macular degeneration to join the search for drug(s) that may be an immediate bridge to treat COVID-19.

Much of Kenney’s research focuses on mitochondria, which play a vital role in disease and death from infections such as COVID-19. Mitochondria may help explain the severity of disease and response to treatment in different ethnic populations and age groups.

Kenney will focus on two crucial COVID-19 studies using her unique laboratory systems:

Determine which promising experimental treatments for COVID-19 patients are most likely to benefit which patients.
Determine the role of mitochondria in susceptibility to severe COVID-19 disease and death in different ethnic/racial populations and age groups.

UPDATE: DEF Researchers Making Progress in the Fight to Defeat COVID-19

Join us and others in supporting this work. At this critical juncture, any financial help you are able to provide to our vital research efforts to stop the scourge of coronavirus is greatly needed and deeply appreciated.

Click here to DONATE BY MAIL

Click to DONATE ONLINE:

For more information on COVID-19 go to www.coronavirus.gov

Cancer in the EYE: Unexpected Thought

When you think of cancer, most of us do not think about the eye or vision. Though rare, cancer can start inside or outside of the eye. If cancer starts inside the eyeball it’s called intraocular and if it starts outside the eye (eyelid or in the eye socket) then it’s called extraocular tumor. It can occur in both children and adults. Most major eye centers have specialists who are trained in the diagnosis and treatment of eye cancers.

Here are a few types of cancer in eye:

Eye Cancer in Children: The most common cancer seen in the eye of children is retinoblastoma. This occurs in children at very early age so these are the youngest cancer patients. This cancer starts inside the eye and affects the retinal cells. This is a cancer that presents very quietly, the child has no pain, no complaints and plays happily without any problem until one day parents notice that the pupil of the eye has some abnormal ‘White Glow’ (leukocoria) rather than the usual ‘red-eye’ reflection seen in a photo—that can be the first sign of retinoblastoma. So, it requires prompt evaluation by an ophthalmologist. Retinoblastoma is a curable cancer but if it is not treated on time, it can grow quickly and fill the eyeball. It can lead to loss of vision and life-threatening problems.

At the later stage of this cancer, the only one way to survive is to remove the eyeball (enucleation). Like many of other types of cancer, retinoblastoma has a genetic component so genetic testing needs to be done. The tumor begins with the RB1 gene mutation that stimulates retinal cells to develop into a tumor called a retinoblastoma. The RB1 mutation can be inherited from the parents, but in some cases it is sporadic and not inherited. There are various treatments such as surgery, chemotherapy, radiotherapy etc. to cure retinoblastoma cancer. Rarely it can spread beyond the eye.

Eye Cancer in Adults: The development of a tumor in the back of the eye in adults can be from a metastatic cancer from elsewhere in the body or can arise in the eye itself. The most common primary eye cancer is called uveal melanoma and is a cluster of rapidly growing cells underneath the retina, which can lead to vision loss. The tumor can also appear as a dark black spot on the iris. Ideally the uveal melanoma can be treated when the tumor is still only in the eye.However, unfortunately, in approximately 50% of patients the uveal melanoma spreads (metastasis) to other part of the body, making it the most dangerous eye cancer in adults. Depending upon its location the uveal melanoma may not cause early symptoms but the patient may experience blurred vision or large numbers of floaters. The uveal melanoma can be diagnosed only when an ophthalmologist or eye care specialist examines your eye. What is the main cause of uveal melanoma? How it starts, grow and spread? These questions are still unanswered. The risk of this cancer increases in persons having fair skin (white), light eye color and inability to tan. There are certain changes in the genes linked to uveal melanoma. Currently the most common are GNAQ and BAP-1 gene mutations that are associated with greater risk of metastasis, where it spreads to other parts of the body. The standard treatment of this tumor is fine-needle aspiration biopsy (FNAB), brachytherapy (radioactive material inside a small capsule placed next to the tumor), radiation therapy and possibly enucleation.

Metastasis to Eye: Finally, the other types of cancers found in the eyes are because of the spreading of a primary cancer (from a distant site such as the breast, lung or liver) to the eye. Sometimes an eye exam can identify a metastatic tumor before the primary tumor is recognized elsewhere in the body. Examples of cancers that spread to the eye are breast cancer in women and lung cancer in men. Less commonly, the prostate, kidney, gastrointestinal and blood cancers (leukemia and lymphomas) can spread to the eye. Treatment depends on the type of cancer involved.

Eye Damage from Chemotherapy: Eye problems can also develop through the side effects of chemotherapy or hormone therapies given for tumors outside the eye. When a person has any type of cancer, they often must undergo treatments with chemotherapeutic drugs. A commonly used cancer drug is called cisplatin. When treated with cisplatin, there can be damage to the retinal pigment epithelial cells in the inner part of the retina. Hemorrhages or bleeding can occur within the retina itself and vision can decrease temporarily. If a person is undergoing cancer treatments, it is a good idea to have their eyes checked, especially if they are having any vision problems. The chemotherapy does not actually cause cancers but only side effects.

Therefore, if you are having any decreased vision, it is always makes sense to have a good eye examination to identify any problems at early stage.

Mitochondrial Revolution: New Hope for AMD and Aging Diseases

How many times have we heard: “This field has been thoroughly studied, and we know all there is to know; there is no reason to continue investigating, because there is nothing more to find out on the subject”? This has been the attitude of some researchers with respect to the importance of mitochondria and diseases. For more than 50 years, we have known that mitochondria, which are the “batteries” of the cell, are critical for energy production. But many believed they did not have other major roles in the health of the cell, so when it came to developing drugs against diseases, mitochondria were overlooked.

That idea has now been turned on its head.

Led by Discovery Eye Foundation (DEF) Research Director Dr. Cristina Kenney, the Mitochondria Research Group believed that, to really discover something new, you have to look in novel areas. This group has done just that. Using the transmitochondrial cybrid model, which are cell lines with identical nuclei, but with each line containing mitochondria from a different person, they have shown that the mitochondria have major regulation powers over cell behavior and expression of disease-related pathways. This is significant, because the mitochondria then become a target for therapies to combat diseases.

Kenney’s group is investigating various drugs and substances that will keep the mitochondria healthy and, ultimately, improve the health of the retinal cells in age-related macular degeneration (AMD). But it does not stop there. This same approach to developing mitochondria-targeting drugs is being pursued for drugs to treat Parkinson’s disease, Alzheimer’s disease, leukemia, various cancers, heart failure, thrombosis, stroke, diabetic retinopathy, Leber hereditary optic neuropathy, and even liver toxicity from acetaminophen.

The continued support from DEF, especially in the early stages of the mitochondria research, has fostered a new area to be opened up, specifically for AMD and diabetic retinopathy. In turn, this has allowed new collaborations among Kenney and researchers from the eye field, and laboratories studying the brain and neurodegeneration, cardiology, cancer therapies and methods to reduce side effects from cancer drugs. Kenney’s discoveries using cybrids have revolutionized the field of mitochondrial research, showing that mitochondria have wide-ranging biological effects never imagined and opening up the field of mitochondrial therapy to careful investigation.

You can help make a difference by supporting DEF’s sight saving research. Help our researchers advance AMD research by donating today!

Lauren Hauptman
Lauren Hauptman Ink

Help DEF Unlock$100,000Matching Gift