Wednesday, April 9, 2014
Ghanshyam and the Magical Cysteamine Patch
The most exciting surprise at the Cystinosis Research Foundation family conference this past weekend was when Kevin Partington pulled up his sleeve to reveal a patch on his arm. He wasn't quitting smoking or going through menopause. The patch was a novel cysteamine delivery system developed by Dr. Ghanashyam Acharya.
Dr. Acharya was introduced to the cystinosis community at the 2013 conference, and he made quite a splash with his energy, enthusiasm and unbridled optimism. He was recruited to the fold by Dr. Jennifer Simpson to develop a better way to treat corneal cystinosis. Together they came up with a nanowafer that is placed on the surface of the eye like a contact lens, which releases cysteamine gradually for a day, and maybe up to a week at a time. Currently the only treatment for corneal cystinosis is Cystaran eye drops, which must be applied every waking hour to eliminate corneal crystals. Dr. Simpson has since used confocal microscopy and a mouse model of cystinosis to show that the wafer is much more effective at reducing corneal crystals than eye drops. Hopefully we'll have a clinical trial in the near future!
Something else Dr. Acharya talked about at that 2013 conference was his previous experience using nanotechnology and microparticles to create longer acting drug formulations of felodipine, risperidone, progesterone, and paclitaxel. The new formulation of the antipsychotic risperidone can be given as an injection at 6 week intervals, which has obvious benefits for people with schizophrenia and problems with medication compliance. My mind started racing as I imagined what a long acting version of cysteamine could mean for patients with cystinosis. We love Procysbi, which is every 12 hours, but I still worry about the fluctuations in Sam's cystine levels. I was picturing something like a depot shot, given maybe once a week, or even once a day. I talked with other families that morning who had come to the same conclusion. I was so excited about the idea that I submitted a question on an index card at the Q&A physician panel, addressed to Dr. Acharya, to see whether he believed it were possible to create a depot shot for cysteamine. His response was simple and confident. "Yes, I can do that."
But there were naysayers on the panel, and their reasoning made sense. They said things like, "The amount of medication you need to deliver would make it impossible. We're talking about grams of cysteamine!" I think a lot of people felt deflated by these remarks, including myself. But Ghanshyam insisted he thought it could be done. The gauntlet had been thrown down, and the wheels in Ghanshyam's head started moving.
Fast-forward one year to the 2014 Day of Hope Conference. Ghanshyam brought a prototype patch with him, and after his talk updating us on the cysteamine nanowafer for the eyes, he gave us the quick run-down on how he developed it. He said he went back to Baylor after the conference and rounded up his four post-docs, put their other research on hold, and brainstormed for a solution. The main problem was the amount of drug to be delivered. Most skin patches, like fentanyl, estrogen and nicotine patches have very small amounts of drug (like micrograms), and this allows the drug to passively diffuse through the skin and into the bloodstream. A cysteamine patch would require an active pumping mechanism, and something like this has never been done before.
The physics was way over my head, but basically Ghanshyam invented a completely new model with multiple layers that are able to convert the mechanical energy of body movement into electrical energy that could pump the cysteamine into the skin. He calls it something like a quantum kinetic transdermal patch. He thinks he can get 500 mg, or half a gram, of cysteamine into the patch, and his goal would be to have it last 3 days. The advantages of the patch are obvious. Medication compliance would go to 100%, and the peaks and troughs associated with every 6 hour dosing would be flattened into a continuous basal rate of drug delivery. This would likely mean that less cysteamine would be needed per patient, and side effects would probably be minimal. The patch may also solve the problem that Dr. Dohill has pointed out, where he found that 2 hours after drug ingestion, cysteamine cannot be detected in tissue. The patch could mean stable cysteamine levels all the time, with better predictability of cystine levels in cells.
I was able to talk with Ghanshyam on Friday night at the dinner, and he told me how he loved to solve seemingly impossible problems. He said you can never take no for an answer. He told me he used to work at NASA, and there he learned the motto "failure is not an option." He said he's not in this business for the money. He just wants to find solutions, and to make life better for children and adults with cystinosis. I propose we clone one hundred more Ghanshyams.
On Saturday when families were sharing the challenges and silver linings of living with cystinosis, Ghanshyam's wife took the microphone for a moment. They were just married in the last year. She said that right after they were married, Ghanshyam would wake up at 2 o'clock in the morning and tell her he needed to go to the lab. She said she thought he was crazy, but she said that after coming to the Day of Hope conference and meeting the cystinosis families, she understands why he works tirelessly and with such urgency. She said she would never question his late night lab antics again, to much applause and laughter.
Ashton and I joked at the conference that if we ever had another son, we were going to name him Ghanshyam. At the time it was an easy declaration to make, because after having a second child diagnosed with cystinosis, we have felt like we are probably done having kids. But with the patch and a possible cure in the pipeline, taking another roll at the dice might be in the future.