‘Childhood Alzheimer’s’ Patients Benefit from KGI-hosted Workshop
Chris Hempel was notified in May that the orphan drug designation application she filed in February at a workshop hosted by KGI's Center for Rare Disease Therapies had been approved by the U.S. Food and Drug Administration.
But, the approval is only the beginning of what can be a long process.
Hempel's 6-year-old twin daughters suffer from Niemann Pick Type C, a rare and fatal genetic cholesterol disease that is often referred to as the "childhood Alzheimer's" because it causes severe dementia in children. The girls, Addi and Cassi, are among about 150 children living in the United States with Niemann Pick Type C and approximately 500 worldwide.
Ian Phillips, PhD, KGI's Norris Professor of Applied Life Sciences and director of the Center for Rare Disease Therapies, had heard about Hempel and her twins before the workshop.
"I know she's so dedicated to finding a cure for her own children. It was incredible news to hear that her application was approved."
Phillips said Hempel's success underscores what the Center is trying to do: Help patients with rare diseases.
Hempel, who lives in Reno, Nevada, filed her application with the support of Children's Hospital and Research Center in Oakland, California, for a sugar compound called cyclodextrin, which has shown promise in cats and mice that have the same progressive neurological disease.
"Cyclodextrin has the miraculous ability to pull cholesterol into its core," Hempel said. "The compound is used frequently to make cholesterol-free products such as salad dressings and butter and is the main ingredient in Febreze air freshener. But when put into the bloodstream or brain, cyclodextrin could be a potentially lifesaving treatment and help save my girls from progressing into a state of complete dementia."
During the workshop, officials from the FDA met with pharmaceutical and biotech company representatives, academics and patient advocates like Hempel to walk them through the application process for orphan drug product designation.
The workshop was designed to demystify the process so more companies and individuals will pursue development of drug therapies for people who are suffering from rare diseases.
"For me and a lot of people, the FDA can be a very intimidating organization," Hempel said. "What I learned is they really want to try to help people move things along and get their applications filed."
To receive orphan designation, the proposed drug therapy must target a rare disease (one with a patient population of 200,000 or less), and it must show promise for treating the condition.
Only about 60% to 70% of applications are approved. Hempel said the fact that their application was successful shows that an individual doesn't need the backing of a pharmaceutical or biotech company to win approval for an orphan drug application.
Currently, she is working on a similar application for the European Medicines Agency, the European equivalent of the FDA, with a mother in the EU whose child also suffers from Niemann Pick Type C.
The Hempels received a compassionate use Investigational New Drug (IND) approval from the FDA last year that allows them to infuse the compound into their daughters' bloodstreams through an IV. They have since determined through research studies that cyclodextrin does not readily cross the blood-brain barrier.
The girls' physician, Dr. Caroline Hastings at the Children's Hospital and Research Center, is working on a new IND application that would allow doctors to deliver cyclodextrin directly into the twins' central nervous systems so it goes directly to their brains.
Despite cyclodextrin's inability to easily cross the blood-brain barrier, Hempel said she has seen positive results. The girls' overall stability on their feet is better and their ability to swallow has improved.
But they continue to show neurological decline. Recent PET scans show that the twins have a hypometabolism issue spreading in their brains, in a similar pattern commonly found in early onset Alzheimer's.
Animals who receive cyclodextrin directly into the brain have shown huge neurological improvements. The goal now is to figure out how to safely deliver the compound into the human brain, Hempel said.
The Hempels also are looking at starting their own biotech company to develop cyclodextrin for medicinal purposes.
"Given that we have very little pharmaceutical or biotech support , we're going to form our own company to move this compound forward," Hempel said.
Thanks to the FDA approval, the Hempels will receive special tax credits that they can apply to qualified human clinical trial costs and research expenses. They also have the ability to pursue grants from the FDA to help move cyclodextrin through the clinical trial process. The Hempels are working with the company that manufactures TrappsolTM, the brand of cyclodextrin they are using, along with the twins' doctors and the Oakland hospital to move the compound forward and into broader clinical trials.
The Hempels' research, efforts and commitment are chronicled on the twins' website at www.addiandcassi.com.
By Elaine Regus