Ever since getting Emmett’s diagnosis, we have been reaching out to doctors and researchers to find out more about his mutation. There have been a small number of publications about the identification and diagnosis of PIGA-CDG patients, but so far, little to no information about treatments. We’ve made progress in getting that research started, but we now need your help to raise money for the research projects we’ve started, which are described below.
Please help us learn more about this devastating disorder and explore potential treatments for this mutation… there are three ways you can help:
- Purchase a t-shirt (by April 21)… we have two adult styles, a toddler shirt and a baby onesie available. — T-shirt campaign now closed. Please contact me if you would like to purchase a shirt, as we have limited quantities available for direct sale.
- Donate through Paypal for CDG Care. (Please note that a 2.2% processing fee will be taken out of all donations. Please add note designating PIGA Research under Special Instructions.)
- Donate by check to CDG Care, which helps to eliminate any processing fees. Mail a check directly to:
P.O. Box 38832
Colorado Springs, CO 80937-8832
Memo: For PIGA Research
Regardless of where you donate, please make sure to put a note saying that, “The donation is in support of PIGA Research.”
And if you have any questions, both Steve and I are always available to discuss. Thank you so much for your support!!
Research Projects In Progress (Updated March 31, 2018)
Create Cell Lines and Do In-Vitro Testing
We’re working with two researchers at Osaka University (Dr. Kinoshita and Dr. Murakami) to create cell lines for in-vitro (in lab) testing. This allows us to test different supplements and molecules in a cell with the PIGA mutation so we can figure out if the supplements/molecules are safe (and at what dosage). They are recreating the mutation in a healthy cell, but will also be using cell lines obtained from our NIH visit.
This research will help determine if these supplements are effective for use in people with a PIGA mutation (and potentially for other genetic mutations in the same enzyme complex), and to what extent they improve the degree of GPI-anchor deficiency. Furthermore, these tests will lay the groundwork for using (when available) the GlcNAc-PI molecule in humans. This data will be critical in getting Institutional Review Board (IRB) and FDA approval for a trial when the time comes.
Develop an Unmodified Version of the GlcNAc-PI molecule
In one of my blog posts, I mentioned our desire to create the “end product” of Emmett’s enzyme pathway where the mutated gene is. (The molecule is called GlcNAc-PI.) We’re working with a lab in Germany (headed by Dr. Seeberger) to create this molecule, which will be tested on the cells created by Dr. Kinoshita and Dr. Murakami. Ultimately, we hope to create a modified version (see below) that we can test and generate for a single patient trial.
Create a Fly Model of PIGA Deficiency
We’re working with Chow Lab (in the Department of Human Genetics at the University of Utah School of Medicine) to create a fly model of PIGA deficiency to better understand how the loss of PIGA function contributes to disease. It’s very preliminary research to better understand PIGA itself, in the hopes that this might help guide further research. (Read about it on the Chow Lab’s blog here.)
Future / Potential Projects
Develop a Modified Version of the GlcNAc-PI molecule for FDA approval
The GlcNAc-PI molecule needs to be modified to cross the cell membrane and blood-brain barrier, so the molecule needs to be modified to allow it to do that. That’s the version we’d submit for IRB and FDA approval, for use in a human trial. (It’s unknown yet how many iterations might be needed.)
Explore How Other Genes Impact PIGA Phenotype
This would be an expansion on the fly model project described above. For example, exploring to what degree the variation in expression of other genes might correlate to the severity of symptoms exhibited in PIGA patients… like would having a higher expression of Gene A impact how PIGA symptoms are exhibited?
Explore Enzyme Replacement Therapy
This approach would involve direct supplementation of the PIGA protein into the endoplasmic reticulum. Questions about PIGA protein synthesis, permeability of the cell membrane and targeting of the endoplasmic reticulum would have to be resolved.