Rare Disease Mystery: Nodding Syndrome May Be Linked to Parasitic Worm

Rural Uganda village gathering

Caption: Village in the East Africa nation of Uganda
Credit: Centers for Disease Control and Prevention

In the early 1960s, reports began to surface that some children living in remote villages in East Africa were suffering mysterious episodes of “head nodding.” The condition, now named nodding syndrome, is recognized as a rare and devastating form of epilepsy. There were hints that the syndrome might be caused by a parasitic worm called Onchocerca volvulus, which is transmitted through the bites of blackflies. But no one had been able to tie the parasitic infection directly to the nodding heads.

Now, NIH researchers and their international colleagues think they’ve found the missing link. The human immune system turns out to be a central player. After analyzing blood and cerebrospinal fluid of kids with nodding syndrome, they detected a particular antibody at unusually high levels [1]. Further studies suggest the immune system ramps up production of that antibody to fight off the parasite. The trouble is those antibodies also react against a protein in healthy brain tissue, apparently leading to progressive cognitive dysfunction, neurological deterioration, head nodding, and potentially life-threatening seizures.

The findings, published in Science Translational Medicine, have important implications for the treatment and prevention of not only nodding syndrome, but perhaps other autoimmune-related forms of epilepsy. As people in the United States and around the globe today observe the 10th anniversary of international Rare Disease Day, this work provides yet another example of how rare disease research can shed light on more common diseases and fundamental aspects of human biology.

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NIH Research Leads to New Rheumatoid Arthritis Drug

x-ray image of hands

X-ray image of the hands of a patient with rheumatoid arthritis. Note that the joints at the base of the fingers are eroded — and some, like the index finger on both hands, are actually dislocated.
Copyright (2012) American College of Rheumatology.

About 1.5 million [1] people in the US suffer from rheumatoid arthritis (RA). It is a chronic illness in which the immune system, which protects us from viral and bacterial invaders, turns on our own body and viciously attacks the membranes that line our joints. The consequences can be excruciating: pain, swelling, stiffness, and decreased mobility.  Over time, the joints can become permanently contorted, as in this X-ray image.

There are several RA medications on the market, but I want to tell you about a new one called tofacitinib, a pill which the FDA approved late last year [2]. The drug works by targeting a protein called Janus kinase 3, which was discovered by John O’Shea and colleagues here at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 20 years ago [3]. As I mentioned in a previous post it takes a really long time to go from a basic discovery to a drug—in most cases nearly 15 years. This drug has been even longer in the making! Shortly after discovering Janus kinase 3 in 1993, NIAMS researchers also revealed its role in inflammation, leading to a public-private collaboration with Pfizer that has now culminated in the approval of tofacitinib.

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