Déjà vu – Another family affected by a rare disease trying to find a cure

During my trip to San Francisco this week I had the opportunity and honor to meet with Matt Wilsey, one of the parents of a child (Grace) with a rare disease and the President of the Grace Wilsey Foundation. The diagnosis of Grace’s NGLY1 deficiency was recently highlighted in an excellent article in the New Yorker by Seth Mnookin. The article also touches lightly on some of the issues with collaboration, competition between groups and publication. Matt and another parent of an NGLY1 child Matthew Might, published a commentary in January on clinical diagnostics and next generation sequencing. In all of this it is important to note that without these parents pushing there would be no understanding of NGLY1, all the scientific progress is due to them fund raising, funding research and their persistence.

So I met up with Matt in a coffee shop across from the Powell St. BART stop for about 40 minutes. The day before I had given a talk at the ACS meeeting to a small group on why there needs to be open data for rare and neglected diseases. What do I know? This is where it gets fuzzy as on one hand I am a scientist trying to piece together the fragments of biology and chemistry and find connections that might be useful. On the other I have now become a defacto rare disease advocate and champion. I sit in an uneasy position. Its not something I can take lightly. Chatting with Matt half hidden behind the largest bottle of water imaginable, I had a déjà vu moment, seeing the same phenotype time and time again with some rare disease patients/parents. Their optimism, knowledge of everything and everyone associated with the disease is worn front and center. That is in itself a superpower that can open doors. They can say and do things regular scientists could not. They can doorstep high ranking officials at the NIH, FDA, congress and they can get time with the busiest Nobel prizewinners and CEO’s. These rare disease parents have an unwillingness to just accept the disease diagnosis, but to meet whoever it takes that can unearth a piece of the pathway to the cure. This pathway may be long, as Matt presented me with a heavy business card listing the NGLY1 3 line long phenotype. All of these rare and ultra rare diseases are frightening in what they do to the patients and families.

As I am sat there listening, I was mesmerized by the fact that this disease shared some similarities and symptoms to some of the other rare diseases I am acquainted with..Its an enzyme that cleaves sugars on proteins, its symptoms include peripheral neuropathy and there may be proteasomal involvement. After the meeting I introduced Matt to some of the parent advocates who have taken a similar pathway to Matt for their diseases. While Matt is literally at the beginning I also sense that he and others can go faster if they can learn what works / does not work.

So this goes full circle to my talk on needing open data. If scientists could freely share their data and reagents faster progress would be made and any unnecessary repetition could be avoided. How do we catalyze this? I sense this could be very important because what may be learnt from another rare disease might help NGLY1. Conversely data from this disease may help others.

Later that day I am sat at the ACS in a room packed wall to wall with hundreds of medicinal chemists listening to some of the most senior medicinal chemists at the biggest pharmaceutical companies in the USA. The diseases they mentioned were dominated by cancers, the targets predominantly kinases  and in general there was not a heavy emphasis or barely a mention of rare diseases.  There was some occasional mention of collaboration but nothing obviously on openess. So here we are with a great opportunity, put chemists to work trying to develop chaperones for diseases like NGLY1, or thinking of ways to get enzyme replacement therapies that could target where they need to go to work in humans. Sitting there hearing that more and more medicinal chemistry expertize is leaving our shores for China did not fill me with hope, but it did get me wondering what if we could convert a few big pharma chemists to the rare disease cause.

I was kindly introduced to Matt by Ethan Perlstein who himself is doing his bit to help rare disease research including NGLY1. Curing 7000 rare diseases may take a few good medicinal chemists and champions that can make things happen, parents like Matt would be eternally grateful.


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