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(HealthNewsDigest.com) – Niemann-Pick disease type C is sometimes referred to as “childhood Alzheimer’s,” because it often is diagnosed in elementary school-age children and causes progressive mental and physical decline. Kids suffering from it usually die before they turn 20.
While NPC affects just one person in 150,000, there is no specific, FDA-approved treatment for it. There are only drugs that alleviate its symptoms but can’t halt its devastating progression.
A pediatric neurologist at Rush University Medical Center is leading a new research effort to find a life-changing treatment for NPC.
Rush is the first center in the Midwest and one of only four in the U.S. currently screening patients and offering the new drug treatment being studied. The National Institutes of Health, Lehigh Valley in Pennsylvania and Children’s Hospital in Orange County, California, are the other clinical trial sites.
“It’s a horrible disease,” says Elizabeth Berry-Kravis, MD, PhD, the study’s co-principal investigator. “Unlike a lot of other genetic diseases, there’s often no hint that there’s anything wrong when the child is born.
“In the classic form of the disease, these are beautiful, normal kids until they reach school age,” says Berry-Kravis, a professor of biochemistry, neurological sciences and pediatrics at Rush. “Then they start to have trouble with learning, some of them develop motor disturbances, some can’t talk well, some of them develop seizures and behavioral problems or psychosis, and death usually occurs by 20.”
Breakdown in the recycling center
In addition to the symptoms, NPC has another similarity to Alzheimer’s disease. Even though they’re young, patients with NPC have an abnormal buildup of beta amyloid protein in their brains that also is seen in people with Alzheimer’s.
The cause of NPC is different, though. This under-diagnosed disease is the result of a rare genetic disorder that prevents the body from properly processing cholesterol.
“Most people think of cholesterol as the bad stuff found in food, but it’s more complicated than that,” Berry-Kravis says. “The body makes its own cholesterol in each and every cell. It is used to build cell membranes and to produce key proteins we need to live.”
Cholesterol, like many other substances in the body, is processed in a compartment of each cell known as the lysosome. “You can think of the lysosome as a kind of recycling center,” said Berry-Kravis.
In patients with NPC, the recycling machinery is broken. Cholesterol gradually accumulates, and also can’t go where it is supposed to go, resulting in toxicity to the cell.
For unknown reasons, brain cells are particularly sensitive to this abnormal cholesterol processing. The mutation in NPC causes the nervous system to be destroyed slowly, but steadily. Patients struggle with movement, gradually lose the ability to speak and eventually the ability to think.
‘A fighting chance at life’
Berry-Kravis and Denny Porter, MD, at the National Institutes of Health are leading a Phase 2b/3 study evaluating the safety and efficacy of a drug called VTS-270, which is being developed by Vtesse, a Maryland-based biotech company that focuses on treatments for rare diseases.
The active ingredient in the drug therapy treatment known as VTS-270 is a compound called hydroxypropyl-beta-cyclodextrin, which is a sugar-based molecule. This type of molecule also can be found in consumer products such as detergent and air freshener because it can bind to odor-causing molecules.
In earlier animal model studies, researchers saw significant improvements in the lysosome’s ability to process cholesterol when treated with the cyclodextrin. NPC typically causes inexorable neurological decline in both people as well as in mice and cats with NPC, but by administering cyclodextrin into the fluid around the brain, the disease progression substantially slowed in the mice and cats.
The phase I trial of the safety of VTS-270 at NIH conducted by Porter, combined with data from patients treated at Rush through an expanded access or “compassionate use” protocol, showed that this drug treatment may be able to alter the course of NPC.
Results indicated that the rate of the disease progression significantly slowed down in children treated with the drug therapy, compared to historical patients that were not treated using VTS-270.
The phase 2b/3 trial will determine whether the drug is effective in a larger population compared to a control group that do not receive the drug. “We will be able to gather data required to advance the regulatory process and move toward FDA and European Medicines Agency approval for a treatment for NPC, that previously has never existed,” Berry-Kravis says.
The Vtesse-sponsored prospective, randomized, double-blind, sham-controlled study is being conducted in patients affected by NPC disease. The VTS-270 drug is administered to patients by lumbar puncture (into the spinal fluid) infusion every two weeks. The drug has to be given into the spinal fluid because it cannot move from the blood into the brain.
In the first part of the study, researchers will evaluate the results of three different dose levels of VTS-270 versus a control group. These results will be used to determine the dose level for the second and third parts of the trial.
All participants in the trial will be eligible to receive treatment with VTS-270 in the third part of the trial the open-label extension, until the time of regulatory decisions. The trial will take place in up to 20 centers in the United States and Europe.
“These children deserve a fighting chance at life,” said Berry-Kravis. “This drug therapy has the potential to be the life-prolonging treatment they need.”
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