NBIA NEWS & INFORMATION

August 2019

The long-awaited results from the first international clinical trial for NBIA — testing deferiprone in individuals with PKAN — are in.

They show that the iron-chelating drug slowed the progression of the disorder in older patients with a later-onset, or atypical, form of PKAN, but did not have a similar benefit for younger patients with classic PKAN, which starts in early childhood.

In addition to those findings, the study showed that the drug successfully reduced the amount of accumulated iron in the brain for PKAN individuals, regardless of onset age.

PKAN, or Pantothenate Kinase-Associated Neurodegeneration, and all other NBIA disorders share iron accumulation in the globus pallidus structure of the brain. It remains unclear, however, whether excess iron causes NBIA or is brought on by some other problem.

The results of the trial, which was funded by a European Union grant titled Treat Iron-Related Childhood-Onset Neurodegeneration, or TIRCON, were presented at the Tenth International NBIA Family Conference held May 30 to June 2 in Charleston, S.C. The findings were then published in the July issue of the medical journal, Lancet Neurology.

The lead investigator of the trial in the United States, Dr. Elliott Vichinsky of the University of California, San Francisco Benioff Children’s Hospital in Oakland, discussed the results at the conference. He said that older and younger PKAN individuals showed improvement with deferiprone in dystonia of the lower face and lower legs, as well as in cognitive functioning, especially memory. But the benefit in the younger children, who tend to have a faster-moving, more severe form of PKAN, “wasn’t statistically significant,” he said.

The 18-month trial, which ran from 2012 to 2015, involved 88 patients from the United States, Germany, Italy and England. The trial met the gold standard for research. It was randomized, with some patients getting deferiprone orally and others getting a placebo. Afterward, the trial was extended another 18 months, and the drug was made available to everyone who took part in the trial.

“The drug was well-tolerated, and the safety profile was very good,” Vichinsky told families at the conference.

But because the study did not meet a key goal — showing a statistically important improvement from deferiprone in all age groups — the U.S. Food and Drug Administration hasn’t yet approved it for PKAN. Consequently, Vichinsky encouraged interested families to contact the FDA to advocate for its approval.

To read the full article:

Published Article

To see his presentation, go to the YouTube channel for the NBIA Disorders Association conference here:

Watch Video

April 2019

Two new BPAN grants were awarded in January from the University of Pennsylvania, with crucial input from the NBIA Disorders Association.

In both cases, the grants will enable researchers to build on their previous studies of BPAN, or Beta-Propeller Associated Neurodegeneration, which is fast becoming one of the most common forms of NBIA.

The money for the grants comes from last year’s Million Dollar Bike Ride held in May 2018 by the Orphan Disease Center at the University of Pennsylvania. For the second year in a row, BPAN family supporters rode and managed to qualify for a matching grant of $50,000 from UPenn. Because the riders raised slightly more than the required match, one-year grants of $51,020 each were awarded for the two new BPAN studies.

Our organization writes the request for proposals, and members of our Scientific & Medical Advisory Board review grant applications. The University of Pennsylvania manages the grants, and sends us copies of the scientific reports that grant recipients provide.

Dr. Hong Zhang of the Chinese Academy of Sciences in Beijing, has received a $51,020 grant for BPAN research. He is currently a visiting professor at the University of Massachusetts Medical School.

One new grant will go to Dr. Hong Zhang, who received a grant from the 2017 Million Dollar Bike Ride. Zhang will be able to continue his studies into the functions of the mutated WDR45 gene, which causes BPAN. Zhang, a visiting professor at the University of Massachusetts Medical School and a researcher at the Institute of Biophysics, Chinese Academy of Sciences, in Beijing titled his newest project, “Mechanistic study of WDR45/45B and their binding partner ATG2 in the autophagy pathway of neural cells.”

What that means is Zhang will be studying the role of the protein WDR45 that’s made by the WDR45 gene that causes BPAN. He also will study WDR45B, the protein for the WDR45B gene that causes another neurodevelopmental syndrome characterized by intellectual disability, spastic quadriplegia, epilepsy and cerebral hypoplasia. Specifically, he’ll be looking at the impact these proteins have in the neural pathway for autophagy, the natural, multi-step process by which the body recycles or cleans out certain toxic materials to maintain proper functioning and stability.

April, 2019

Dr. Lauriel Earley from the University of North Carolina - Chapel Hill, will work on a PANK2 gene therapy for the treatment of PKAN in her newly awarded grant.

Two new grants to study PKAN were awarded early this year by the NBIA Disorders Association in collaboration with two of our European sister organizations, AISNAF in Italy and Hoffungsbaum e. V. in Germany.

These grants mark the first time all three NBIA groups have teamed up to fund research projects.

The organizations received 12 proposals, with eight focusing on PKAN, three on BPAN and one on MPAN. All were evaluated by an International Scientific Advisory Board made up of scientists and clinicians with expertise in the field of rare, neurodegenerative diseases, including NBIA. In a second step, the projects deemed worthy of funding were shared with a Lay Review Board consisting of parents and patient representatives. The lay group had the final say on which projects would be funded.

The members selected two PKAN studies. No proposals to study BPAN or MPAN met the funding standards, so a new call for proposals for these two disorders went out in March.