One of the most anticipated returns to normalcy following the pandemic is the in-person conference. Like the mythical Phoenix bird arising from…
Steve Fialkoff and I weren’t friends at James Madison High School in Brooklyn, NY. We were in the class of 1972; earlier alums include Chuck Schumer, Bernie Sanders, and Carole King. The near-thousand of us self-sorted into three cliques, based on neighborhood. Steve was from Mill Basin, me Kings Highway.
While super-popular Steve was everywhere with his massive blond ‘fro, capturing our experiences with his camera and leading the class in drama productions, I was on the fast track to nerddom. I spent my time in the chem lab with the groovy new teacher in charge, a 24-year-old who showed my bestie Wendy and me how to make bongs and water pipes. But Steve now says he was a closet nerd, a “frizzy-haired, freckle-faced, big-nosed, crooked-smile, toothy guy.”
It wasn’t surprising that Steve became a film editor and now a playwright. What was surprising was learning at age 25 that he had retinitis pigmentosa, after he tripped over a seat in a darkened theater and had a few other stumbles.
The more than forty types of RP, each caused by a different gene, affect more than a million people worldwide. But the same mutation can manifest differently among individuals, even within the same family. Links between genotype – the mutations – and phenotype – the symptoms – are complex.
Steve inherited Usher syndrome type 2A from parents who are carriers. Night vision would gradually vanish, then parts of the periphery of his visual field. He would likely lose sight completely in his 60s, the ophthalmologist said, oddly calling Usher 2A “common and mild.” Not much comfort.
A bit of biology. The USH2A gene behind Steve’s RP encodes a protein, usherin, which functions as a cellular glue and scaffold. Usherin maintains the integrity of the rods and cones at the back of the eye that provide vision, as well as of supportive cell layers. Steve calls what I call extracellular matrix and cellular adhesion molecules “cellular poop that suffocates cells.”
The ophthalmologist’s prediction came true when Steve was 56. As the tunnel of his vision inexorably narrowed, Steve signed up for a guide dog, a service he could get once he’d lost 95 percent of his sight. By August 2021, he’d qualified.
Recently, Steve was out walking that dog when his story took a dramatic and unexpected turn: more of the world appeared. During his continuing “wild crazy coincidental ride,” he’s been attempting to recreate the circumstances that may be expanding his visual field. “I realized that something amazing was happening to me.” He thinks like a scientist.
His reasoning and trial-and-error approach identified three common nutritional supplements – curcumin, piperine from black pepper, and ginger – that, when ingested together, seem to be returning some of his vision.
Steve shared his story with me, a half century after we passed in the hallways of James Madison High School.
A Memorable Sunrise
When Steve left his Manhattan apartment building early in the morning of February 8th, 2022, he turned eastward, “right into a blazing fireball of sun coming up between the buildings. I looked down, shielding my eyes, and saw individual hairs on my guide dog’s body and could see his whole head. I started walking, shielding my eyes. The dog did his business and I turned around and looked back to the west, away from the sun. And I could see down the block, the edges of buildings and where sidewalk and curb meet. Normally I couldn’t see where I was until I was a few feet away,” he recalled.
But the sunlight wasn’t as stark a change or as complete as a curtain rising. On his way home, Steve tripped over a few tree gardens – small fenced-off grassy squares that surround trees on Manhattan side streets. When he made it upstairs to his apartment, he told his wife and daughter that he was having “a good RP day.” And indeed he was.
In the kitchen, where Steve had become accustomed to seeing only half of one of the four burners, he now saw three. “Normally I have to put my hand on the stove to find out where to put a pot. My visual field had widened overnight.”
What was happening? Isn’t RP supposed to worsen? Was it the curcumin pills Steve started taking to ward off COVID?
Pursuing a Dietary Link
His initial hunch turned out to be correct. Curcumin is the active part of turmeric. It imparts the signature bright yellow hue of the powdered spice. The source is the plant Curcuma longa, related to ginger. Steve took a supplement called CurcumRx.
His daughter googled “curcumin and RP” and soon found a review article from May 2021 that linked curcumin to helping with several visual conditions, a long section on RP. Excited, Steve skimmed it.
“I thought, holy crap! I’m not crazy, curcumin works! I was taking a quarter of a gram, 250 milligrams.” 3.6 grams daily would be needed for a therapeutic effect in people, and up to 12 grams could be tolerated, the article extrapolated from rat studies.
“So I continued taking it. On March 11 I experienced another bump up in vision, things starting to clear up. I went home from my walk in tears. What had I done in the last few days to get more vision back?”
Steve re-read the review article. He learned that curcumin has been used for thousands of years in traditional Chinese and Ayurvedic medicine, and brought to the west in the 1300s.
Use of the spice was linked to its many “antis” – anti-oxidant, anti-inflammatory, anti-mutagenic, anti-microbial, and even anti-cancer. It’s been tried as a remedy for Alzheimer’s disease, diabetes, cancers, rheumatoid diseases, allergies and asthma, atherosclerosis, lung infections, chronic intestinal inflammation, autoimmune diseases, AIDS, psoriasis, and more.
More science: What Steve had first noticed was an association between ingesting the spice and better vision. If increasing the dose made him see even better, that would be a correlation. And if he could identify a biological explanation for the effect, he’d be on the road to demonstrating causation.
And yes, it all makes sense.
The Biology of Retinal Damage
Curcumin helps the photoreceptor cells (rods and cones) of the retina that provide vision. These cells, specialized neurons, are under great oxidative stress from being bombarded with light, as are nearby supportive cells and other neurons that send visual information to the brain.
In oxidative stress, chemical reactions spawn unstable forms of oxygen called free radicals, which have unpaired electrons. The free radicals damage biomolecules, especially delicate DNA. Several diseases of the retina arise from an imbalance between formation of free radicals and their removal.
Curcumin has been used to quell oxidative stress in several retinal diseases, including uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, tumors, and several genetic conditions.
In addition to scavenging free radicals, curcumin affects the pigment rhodopsin, aka visual purple. Rhodopsin is the most abundant protein in the rods, dotting the surfaces of the layers of outer membranes, providing night vision. In some forms of RP, rhodopsin misfolds as it forms, trapping bits of surrounding membrane, gunking up and killing the rod cell. In rats with these types of RP, curcumin maintains rod integrity.
Because high doses of curcumin are necessary for medicinal effects, chemists synthesize analogs, related molecules that enter the bloodstream faster. They’re also working on ways to deliver curcumin, fashioning nanoparticles out of liposomes, egg white, sand, algae, and even silk protein. Of course, analogs and nano-anything add to cost.
But Steve read about a better boost: a chemical in black pepper, peperide, which slows absorption of curcumin in the liver and the intestines. It stays in the bloodstream longer, a property called bioavailability. Would peperide make curcumin hang around long enough so that Steve could see the hairs on his guide dog? The pepper component reportedly increases bioavailability of curcumin 2000 percent.
Enter the Vietnamese Restaurant Effect
For some food combinations, like peanut butter and jelly, and now curcumin and black pepper, the whole is greater than the sum of the parts. But there was more to the visual effect than adding pepper, of which Steve isn’t a big fan. So like PB+J plus banana, ginger joined the other two spices.
Steve followed the clues. What had he eaten that had been especially spicy before his vision improved? He recalled, vaguely, some ginger chicken from a Vietnamese restaurant. “So I had my daughter look at the credit card from February to see if there was a charge for the restaurant before February 8, when I had the first bump up in vision. We’d ordered from there on February 4! I did some research and read that people in India and China add ginger and black pepper to turmeric to make it work better.”
Steve loves to cook. But he couldn’t quite recreate the restaurant’s spice mix that might have cleared his vision. He grew frustrated.
“Two months later I said, let me order the damn chicken again. Maybe there’s something magical in it. So I ordered it again and I got a bump up in vision.” His daughter found the recipe online. “And sure enough, the restaurant marinated ginger slices in black pepper, oil, and garlic.”
So Steve invented his own take on pepper-and-turmeric-infused ginger strips, eating 6 to 8, with rice or pasta, every few days. And he upped the curcumin pills to 500 milligrams.
The calendar provided the remaining clues.
Rat studies showed that piperine took 48 hours to escort curcumin into the retina’s blood supply. “I’d ordered the ginger chicken February 4 and had leftovers until February 6 … so I’d eaten it 3 days in a row. On February 8th there was the seemingly overnight change in vision. The same thing happened again. I had ginger chicken March 8 and a bump in vision March 11.”
Spreading the Word
The ginger strip concoction seems to be helping. In July, on his morning walks, Steve could see scaffolding and poles at the ever-present Manhattan building sites that he hadn’t before. “I could see metal bars and garbage cans and people – that was a big change.” Now he’s trying to keep the dietary intervention as consistent as possible to maximize the good-vision days – sometimes his world is still shrouded in shades of gray and black.
In April a visit to a retinal disease clinic showed improvement in visual acuity, the ability to distinguish details of objects at a given distance. But Steve’s RP had worsened since the last assessment six years earlier. So, there really was no way to measure whether progression had slowed. When Steve mentioned his culinary intervention, “the doc said, ‘that’s nice, we’ll see you in a year.’ But I didn’t blame them for being skeptical. I had no recent test results, just my memory of how I see.”
When Steve contacted the Foundation Fighting Blindness, he was put in touch with a science writer, who advised awaiting findings of double-blinded clinical trials. That’s going to be a looong wait, because ClinicalTrials.gov lists only six ongoing trials for Usher 2A RP – two to observe rate of progression of the disease, and four that use antisense oligonucleotides (gene silencers) to target a very specific mutation.
Clinical trials? Really? If a readily available supplement works, go for it!
So Steve spread the word on a listserv, and a few others with RP tried curcumin-piperine-ginger, or had already made similar discoveries. A man cried when he could see his wife’s face. A woman could see her hands on a cutting board – a deficit that had made cooking difficult for Steve, too, seeing the knife but not his fingers. “My goal is to tell enough people to get the ball rolling.”
Treat the Phenotype or Genotype? Rethinking my Gene Therapy Book
My friend Wendy from high school bong-making days had kept in touch with Steve, and recently sent me an article by Ingrid Ricks, who also has RP. That’s how I learned about his remarkable story, which he happily shared.
His final comment stopped me short. “There’s no cure for this thing. No one I know with RP has ever improved. Ever.“
The message of my 2012 book The Forever Fix: Gene Therapy and the Boy who Saved It, was just the opposite, but for a different retinal disease that affects the layer beneath the rods and cones.
My book tells the story of a boy, Corey, with RPE65 retinal dystrophy who was one of the first to regain vision, in days, following gene therapy. Luxturna was the first-ever approved gene therapy in the US, in 2017. Since then hundreds of people with Corey’s form of blindness have regained vision thanks to Luxturna. Steve knew all about it.
But gene therapy has also had some spectacular setbacks, and not just the sad case of Jesse Gelsinger in the early days. Children have died in clinical trials, recently, although it can be difficult to tell whether it was the disease or the treatment at fault.
Some gene therapies simply haven’t worked, or doses in the sweet spot of efficacy without toxicity remain elusive. Cost is a huge issue, even if a gene therapy is one-and-done or infrequent. The first-ever approved gene therapy – Glybera for pancreatitis, in Europe – was taken off the market because nobody would pay for it.
So I came to regret my runaway optimism in the final chapter of The Forever Fix. I’d predicted widespread approval and adoption of gene therapies, for common as well as rare genetic diseases. It was not to be. So far, gene therapy approvals in the U.S. stand at two, as other strategies spring ahead.
And so when a clever combination of widely available and safe supplements restores any vision, that’s great. For some conditions, treating the phenotype – the trait – is more effective, and certainly cheaper and easier, than treating the genotype – the DNA.
Meanwhile, Steve can hardly believe his good fortune, and keeps testing himself. “Did I see that stair step yesterday? Today? Is the lighting different today?”
I hope his world continues to brighten. “I would love to improve enough to see the actors perform my original plays on the stage.”
I’ll bet he will.