Deferiprone (Ferriprox, Kelfer) treatment for PKAN successful in Oakland

Those on Facebook who are fans of Oakland Hematology may have seen this.

From http://abclocal.go.com/kgo/story?section=news/health&id=7267620

OAKLAND, CA (KGO) -- An experimental treatment for a rare and fatal disease is changing the life of a young boy.

When we first brought you this story, doctors at Childrens' Hospital Oakland were about to begin giving him the investigational drug. Now just months later, his parents say it is already making a dramatic difference.

Watching 12-year-old Travis Brown raise his arm to his chin may not seem like an amazing accomplishment, unless you had seen him just a few months ago.

"He couldn't move his arms at all," says his mom Pattie Brown. "One arm was pinned to his side where you couldn't lift it, even to put a thermometer in it."

Last year, Travis' mother and father had to wheel him into Children's Hospital Oakland, lying in a toy wagon. A rare condition known as PKAN, caused by a concentration of iron in the brain, had left his body a twisted lump.

"He couldn't lift his head, couldn't lift a muscle," Pattie says. "Couldn't move hands, couldn't do anything."

Moving from that wagon to sitting up in a wheel chair is just one sign of Travis' dramatic improvement. But, the boy who could not move his arms can now be seen shadow boxing with his father.

"I think Travis is like a miracle," says Dr. Elliott Vichinsky.

Vichinsky believes the difference is an investigational drug called Deferiprone. It is not approved in the U.S., but he was able to obtain a compassionate use waver from the FDA to treat Travis.

"I got approval to use this drug called Deferiprone, which is the only kelator or in another words a drug that removes iron, and its the only one in the world that can get into the brain and take iron out," says Vichinsky.

Vichinsky had already used Deferiprone to treat a different iron-related condition, but nobody knew if the drug could remove enough iron from the brain to reverse the severe symptoms of PKAN.

Within months of his first treatment, his parents began to notice the changes. Travis can now sit and hold his head up on his own. His legs have regained enough flexibility that doctors are even discussing possible surgery to straighten his feet.

"I mean, to have him stand again, it would be a miracle," says Jacob Neufeld at Children's Hospital.

Still, nobody knows if Travis will return to being the completely healthy child who had enjoyed camping and hiking just a few years ago. Doctors caution that they do not know the long term effects of Deferiprone.

"Every day I walk like on eggs. I worry that if the improvement he shows is going to continue and stay that way or will it not, but right now the storm cloud has lifted over Travis," Vichinsky says.

So has the veil of silence. Travis' disease had progressed to the point that he had not been able to speak for months, until one recent morning when his mother finally heard his voice again.

"First he said, 'Momma.' First, I thought 'no.' Then this morning, he said 'Momma' again and I said, 'What did you say?' He said, 'Momma,'" Pattie says.

Doctors at Children's Hospital are now planning a clinical trial in the spring with up to 30 children suffering from PKAN.

To contribute to the Travis Brown Foundation, make checks payable to "Rotary International --Travis Brown" and send to:
Lathrop Police Department
15597 7th Street
Lathrop, CA 95330

Written and produced by Tim Didion.
(Copyright ©2010 KGO-TV/DT. All Rights Reserved.)

This is of course wonderful news for those with this illness, but I want to bring attention to the statement highlighted in bold. Deferiprone is the ONLY chelator that is a small enough molecule to penetrate the brain (I want to point out that natural chelators like IP6 also do this, but they are not as strong). My feeling on this is that at some point in every chelating patient's life, deferiprone should be used as a chelator. As patients are living longer, the issue of iron in the brain is becoming more recognized and it does need to be addressed. This alone should justify its approval in the US. I know how frustrating it is for doctors like Vichinsky, who cannot prescribe this drug through normal channels and it is far more frustrating for patients.

Dear FDA, approve deferiprone and do it NOW!

Yes I saw it Andy, i really wish Dr. Vichinsky all the best and that soon Deferiprone will be approved in the States

Manal

Thats a really great news,i hope Defriprone will soon be approved in US .

Zaini.

What great news!  I hope that this child completely recovers and that he is able to resume speaking, hiking and camping again really soon. 

Sharmin

can i know who is Dr. Vichinsky? i will be pleased if anyone tell me?

Dr Vichinsky is an incredible doctor who leads one of the best, if not the best, thalassemia centers on earth. People think I do a lot for thals, but my efforts are only a small dot compared to what Dr Vichinsky has done for thals around the world. He has been a constant inspiration for me and it has been a true privilege to meet him at two conferences.

http://www.childrenshospitaloakland.org/doctors/elliott_vichinsky.asp

Elliot Vichinsky, MD is the Director of Hematology/Oncology at Children's Hospital and Research Center at Oakland, the Northern California Sickle Cell Center, the California Thalassemia Center and the California Reference Hemoglobin Laboratory. Dr. Vichinsky diagnoses and treats children with blood disorders, cancers and tumors.

He founded and directs the largest hemoglobinopathy center of sickle cell disease and thalassemia in North America. The center is dedicated to developing therapy to treat and cure the 200,000 infants born worldwide each year with sickle cell or thalassemia. He is working with the World Health Organization in studying the worldwide public health problem of thalassemia and sickle cell disease.

He has been instrumental in implementing newborn screening programs for blood diseases in California and throughout the world. Dr. Vichinsky was responsible for the development of the Blood and Marrow Transplantation Program, which has cured hundreds of children who had sickle cell anemia, thalassemia, and various cancers. He has developed techniques that make blood safer for chronically transfused patients. These patients often suffer from iron overload as a result of either transfusion therapy or genetic mutations. Iron overload causes thousands of deaths each year. Dr. Vichinsky has been an international leader in developing drugs to remove excess iron and non-invasive equipment to measure iron in the body. He has also been a leader investigating novel drugs that turn on hemoglobin-producing genes which enable sickle cell disease and thalassemia patients to produce their own healthy blood.

Dr Vichinsky is the Medical Director of The Cooley’s Anemia Foundation. Dr. Vichinsky’s focus is on translational research in hemoglobinopathies and iron overload.

Dr. Vichinsky is Editor in Chief of the journal, Pediatric Hematology and Oncology. He has been a reviewer for several journals, has published literally hundreds of articles, abstracts, and book chapters, and has presented widely on the topics of sickle cell disease and thalassemia.

Dr. Vichinsky has been the principle investigator of several studies including, but not limited to the following: national preoperative transfusion study; neuropsychological dysfunction in sickle cell disease; cerebral ischemia: early diagnosis and effect of intervention on cerebral metabolism, acute chest syndrome study; safety study of infusions of VX-104 in patients with sickle cell anemia; decompression coring versus conservative therapy for avascular necrosis of the hip in sickle cell disease; E beta thalassemia response to chemotherapy; secondary hemochromatosis in beta thalassemia and sickle cell disease.

In addition, Dr. Vichinsky has been the Primary Investigator of several chemotherapy intervention trials in sickle cell and thalassemia including: hydroxyurea, erythropoietin, arginine butyrate, sodium phenyl butyrate, magnesium, and gardos channel inhibitors. His major research interest has been in transfusion therapy and iron overload and has served as principle investigator on studies evaluating allo-immunization, red cell pheresis, and efficacy of transfusion therapy.

He directs an iron overload program which evaluates non-invasive iron measurements (ferritometer, T2* MRI) and new iron chelation therapies. Children’s Hospital & Research Center Oakland is one of four places in the world with a SQUID (Superconducting Quantum Interface Device) that can accurately non-invasively determine the body’s iron. Children's is one of only a handful of hospitals in the nation using special software technology, T2*, in combination with a Magnetic Resonance Image (MRI) machine to safely measure iron levels in a child’s heart.

What connection can anyone see here .. ?
WHY would they be deficient in pantethine AND treated by deferiprone.. ?

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration
Anil Ranaa, Erwin Seinena, Katarzyna Siudejaa, Remco Muntendamb, Balaji Srinivasana, Johannes J. van der Wantc, Susan Hayflickd, Dirk-Jan Reijngoude, Oliver Kayserb, and Ody C. M. Sibona,1
+ Author Affiliations

aDepartment of Cell Biology, Radiation and Stress Cell Biology, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands;
bDepartment of Pharmaceutical Biology, GUIDE, University of Groningen, 9713 AV Groningen, The Netherlands;
cDepartment of Cell Biology, Molecular Imaging and Electron Microscopy, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands;
dDepartment of Molecular and Medical Genetics, Pediatrics, and Neurology, Oregon Health and Science University, Portland, OR 97239; and
eDepartment of Laboratory Medicine, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9713 EZ Groningen, The Netherlands
Edited by Barry Ganetzky, University of Wisconsin, Madison, WI, and approved February 22, 2010 (received for review October 22, 2009)

Abstract
Pantothenate kinase–associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN.

coenzyme AmitochondriaPKANoxidative stresslifespan
Footnotes
1To whom correspondence should be addressed. E-mail: o.c.m.sibon@med.umcg.nl.

a wonderful news indeed .. thanx for sharing this, Andy ...


Umair