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Discovery clears way for clinical trial to treat devastating neurologic disorder

New compound, tested in mice and human cells, corrects abnormalities that cause the disease
a young boy in a wheelchair, being kissed by his mother
Carter Anderson of Butte Falls, with his mother Courtney, during an appointment at OHSU, late 2017. Carter was diagnosed with PKAN - Pantothenate Kinase-Associated Neurodegeneration, a genetic disease that affects his ability to walk, talk, eat and control basic movements. (OHSU/Kristyna Wentz-Graff)

Research has revealed a promising new treatment for a rare and debilitating neurologic disorder that disproportionately affects children.

Oregon Health & Science University medical geneticist Susan Hayflick, M.D., and neurologist Penny Hogarth, M.D., lead a team that has developed a model to treat Pantothenate Kinase-Associated Neurodegeneration, or PKAN. The new development culminated 28 years of research.

The basic science research is expected to move quickly into human studies in PKAN patients. A national clinical trial funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health, is slated to start in the coming months.

In a study published today in the journal EMBO Molecular Medicine, researchers led by Suh Young Jeong, Ph.D., at OHSU, and Ody C.M. Sibon, Ph.D., at University Medical Center Groningen in the Netherlands, demonstrated an oral treatment that normalized the molecular anomaly in mice within two weeks of starting the treatment.

Carter sits in his wheelchair as doctor hayflick, wearing a white coat, seated, to the right, examines his legs
Medical geneticist Susan Hayflick, M.D., examines Carter in 2017. Hayflick and neurologist Penny Hogarth, M.D., lead a team that developed a model to treat the disease, a culmination of 28 years of work. (OHSU/Kristyna Wentz-Graff)

While the transition from the lab to the clinic usually takes many years, OHSU researchers say the nature of the compound and its target disease allows it to move swiftly into human studies.

The OHSU team has been working closely with PKAN patients and families and the U.S. Food and Drug Administration for the last four years to develop the treatment in an accelerated, low-cost model. The researchers say this approach will not only enable them to get a promising compound to patients faster, but will also allow them to keep its eventual cost to families to a minimum.

“We are physicians, and our first priority is to try to relieve the suffering this disease causes,” Hogarth said. “But we are also socially responsible members of society, and we want to challenge the current for-profit model that has resulted in skyrocketing drug costs, especially for rare diseases.”

People with PKAN lack a chemical necessary to metabolize a vitamin in the brain. Without normal levels of this metabolite, part of the brain degenerates, which causes severe problems with walking, coordination, vision, speech and swallowing. Patients’ intellect is preserved, but the condition causes severe muscle spasms, to the point of breaking bones, and eventually leaves patients unable to move, walk or eat independently.

The new compound, tested in mice and in human cells, works by correcting the abnormalities that cause the disease.

Carter, in his wheelchair, smiling with his parents.
(Left to right) Carter goofs off with his parents Courtney and Blair Anderson. People with PKAN lack a chemical necessary to metabolize a vitamin in the brain. Without normal levels of this metabolite, part of the brain degenerates, which causes severe problems with walking, coordination, vision, speech and swallowing. (OHSU/Kristyna Wentz-Graff)

With the support of OHSU, Hayflick and Hogarth have formed a nonprofit organization called the Spoonbill Foundation to advance this potential treatment. Funds raised by patients and families have facilitated the development of the compound and will support clinical trial costs not covered by the NIH grant.   

Together with European collaborators who have formed a sister foundation in the Netherlands, the OHSU researchers are collaborating with Oregon State University’s Food Innovation Center to scale up production of a base chemical that can be formulated into a strawberry-flavored syrup.

If this nonprofit model succeeds, Hogarth and Hayflick said they believe other academic investigators may use it to develop treatments for other rare diseases that are affordable for families.

“We are blazing a path that can be taken by others,” Hayflick said.

Some of the research described in the study was supported by the National Institute of Neurological Disorders and Stroke of the NIH, award NS109083. In the interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regards to this research, Drs. Hayflick and Hogarth serve as uncompensated founders and executives of the Spoonbill Foundation, a not-for-profit 501c3 organization that is involved in the development and commercialization of a compound for PKAN. Review details of OHSU's conflict of interest program to find out more about how we manage these relationships.

 

 

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