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NIH Undiagnosed Diseases Program

Emory team part of undiagnosed conditions challenge

An Emory team of geneticists and genetics counselors is participating in the Clarity Undiagnosed competition, hosted by Boston Children’s Hospital and Harvard Medical School.

The team is led by genetics counselor Dawn Laney MS, CGC, CCRC. Team members include: Madhuri Hegde, PhD, William Wilcox, MD,PhD, Michael Gambello, MD, PhD, Rani Singh, PhD, RD, Suma Shankar, MD, PhD, Alekhya Narravula, MS,CGC, Kristin Cornell, MS, CRC, Cristina da Silva, MS, Sarah Richards, MS, CGC and Kimberly Lewis, MS, CGC.

In Clarity Undiagnosed, five families of patients with undiagnosed conditions provide DNA sequence information and clinical summaries to up to 30 competing teams. The teams then do their best to interpret the data and provide answers, and a $25,000 prize will go to the team that solves the mysteries in the most complete way.

At the discretion of the families, short videos of the patients may be available to investigators through producers of a forthcoming documentary film, Undiagnosed, but the teams are barred from direct interaction with the families. A glimpse of some of the families is possible by viewing the trailer. Teams have until September 21 to submit their reports and the results of the competition will be announced in November.

Boston Children’s and Harvard held a similar competition in 2012, which attracted teams from all over the world.

The competition grows out of the NIH-sponsored Undiagnosed Diseases Network; Emory pharmacologists Stephen Traynelis and Hongjie Yuan have been working with the related Undiagnosed Diseases Program based at NIH (very complex 2014 paper, blog post on personalized molecular medicine).

Posted on by Quinn Eastman in Uncategorized Leave a comment

Personalized molecular medicine part 3

This is a continuation of previous posts on individualized treatment for infantile-onset epilepsy, made possible by Emory scientists Stephen Traynelis and Hongjie Yuan’s collaboration with the NIH Undiagnosed Diseases Program. A companion paper containing some clinical details was recently published in Annals of Clinical and Translational Neurology.

Memantine, which was found to be effective for this particular child, is normally used to treat symptoms of Alzheimer’s disease. He has a mutation in a gene encoding a NMDA receptor, an important signaling molecule in the brain, which hyperactivates the receptor. Treatment with memantine reduced his seizure frequency from 11 per week to three per week, and eliminated one type of seizure, myoclonic jerks. It allowed doctors to taper off conventional anticonvulsant drugs, which were having little effect anyway. His cognitive ability has remained unchanged.

The team also discovered that the compound dextromethorphan, found in many over-the-counter cough medicines, was effective in the laboratory in counteracting the effects of a GRIN2A mutation found in another patient. However, these effects were mutually exclusive, because the molecular effects of the mutations are different; memantine helps L812M, while dextromethorphan helps N615K.

Yuan and Traynelis report they have an Fake Oakleys ongoing collaboration with UDP investigators to analyze the effects of mutations in NMDA receptor genes. That means more intriguing case reports are coming, they say.

Tyler Pierson, MD, PhD, lead author of the clinical paper who is now at Cedars-Sinai Medical Center in Los Angeles, and David Adams, MD, PhD, senior staff clinician at NIH, provided some additional information on the patient in the study, shown here in a Q + A format. Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Personalized molecular medicine part 2

This is a continuation of the post from last week on the early-onset epilepsy patient, whom doctors were able to devise an individualized treatment for. The treatment was based on Emory research on the molecular effects of a mutation in the patient’s GRIN2A gene, discovered through whole exome sequencing.*

For this patient, investigators were able to find the Ray Ban Baratas cause for a previously difficult to diagnose case, and then use a medication usually used for Alzheimer’s disease (memantine) to reduce his seizure frequency.

Last week, I posed the question: how often do we move from a disease-causing mutation to tailored treatment? Read more

Posted on by Quinn Eastman in Cancer, Neuro Leave a comment

True personalized medicine: from mutation to treatment

Stephen Traynelis and Hongjie Yuan

Stephen Traynelis, PhD and Hongjie Yuan, MD, PhD

How often can doctors go from encountering a patient with a mysterious disease, to finding a mutation in a gene that causes that disease, to developing a treatment crafted for that mutation?

This is true personalized molecular medicine, but it’s quite rare.

How rare this is, I’d like to explore more, but first I should explain the basics.

At Emory, Stephen Traynelis and Hongjie Yuan have been working with Tyler Pierson, David Adams, William Gahl, Cornelius Boerkoel and doctors at the National Institutes of Health’s Undiagnosed Diseases Program (UDP) to investigate the effects of mutations in the GRIN2A gene.

Their report on the molecular effects of one such mutation, which caused early-onset epilepsy and intractable seizures in a UDP patient, was recently published in Nature Communications.

With that information in hand, UDP investigators were able to repurpose an Alzheimer’s medication as an anticonvulsant that was effective in reducing seizure frequency in that patient. [The details on that are still unpublished but coming soon.]

Read more

Posted on by Quinn Eastman in Neuro Leave a comment