Niemann-Pick is highly heterogenous and is characterized by hypervariable manifestations across patients.
Niemann-Pick Disease is a group of disorders affecting 1 in 100,000 live births. What characterizes this disease is its hypervariability in type and presentations, which, in turn, has led to challenges in research and treatment.
Sharon Hrynkow, PhD, Chief Scientific Officer and Senior VP for Medical Affairs at Cyclo Therapeutics, joined HCPLive® on The Rare Disease Report to discuss Niemann-Pick, its different types (especially type C), and the current treatment and research landscape, including an ongoing phase 3 trial of Cyclo Therapeutics's investigative treatment.
She discussed the challenges of diagnosing and treating the disease as well as resources that patients and families can utilize on their journey in dealing with the debilitating condition.
Below is the full episode, including highlights from the conversation.
HCPLive: What is Niemann-Pick Disease?
Hrynkow: It is a defect in how cells in our body process cholesterol. […] It wasn’t until the 1960s at a lab at NIH [National Institutes of Health] where we started to understand Niemann-Pick Type A and B, which is a defect in the enzyme lipid-manufacturing process.
Later on, a scientistic named Peter Pentchev discovered Niemann-Pick Type C, which is different from A and B. This is a defect in a protein, which is very large, in the membrane of the lysosome.
That protein, in 95% of cases, is responsible for the accumulation of cholesterol in the lysosome of the cell. Niemann-Pick is a defect in which cholesterol basically gets trapped in the cells.
The disease can be detected at various stages in the lifespan — usually in childhood, sometimes in infancy. Those children do not survive for long. There’s a type in which toddlers will manifest the symptoms first — those patients tend to survive until the age of 10-14.
And then there are later-onset versions of it. Most patients will unfortunately succumb to the disease until the age of 20. For those who present with symptoms in their 20s—or sometimes up to 50 or 60 years old—they can live for decades with varying amounts of disability.
What is the patient experience with this disease?
It is what’s called a hypervariable disease. The presentations are heterogenous. […] Siblings with NPC1 can present somewhat differently. So, it’s hard to say what’s a typical presentation. What I can say is that it’s a progressive debilitating disease.
For families who receive the diagnosis of NPC for a loved one, it’s a really devasting diagnosis to receive because there are no cures.
Patients will tend to start with neurologic symptoms, which can be minor at first. […] They may experience a certain kind of supranuclear gaze palsy. This is one of the signals that pediatricians will often detect.
Children in early toddlerhood will start to trip and fall unusually. There are challenges with swallowing, and patients over time will start to use food thickeners and other adaptive devices to help them eat.
This can start even after high school. They can be developing seemingly normally and then start to have challenges at, say, 14 or 15. This often goes misdiagnosed as ADHD or other behavioral problems.
Does this disease tend to affect certain populations more than others?
The disease is panethnic. However, like other rare diseases, it tends to be amplified in communities in which there’s consanguinity.
In the Middle East, the prevalence of Niemann-Pick disease can be higher than in other places—and in certain communities in India, and communities that tend to segregate and be close-knit.
In order to have Niemann-Pick disease, a patient has to have a defect in both genes.
What do screening and diagnostic practices look like?
The skin biopsy became the mainstay of diagnosing NPC for decades. With the advent of molecular biology, now we can do genetics and confirm NPC1 diagnosis that way.
Diagnosis is becoming easier when clinicians suspect Niemann-Pick disease. A physician has to think that a patient might have a lysosomal storage disease, and it might be NPC, in order to send them for the genetics to confirm.
As physicians become more aware of Niemann-Pick as a disease, that process is becoming more common.
But many of the patients and families with whom we’ve spoken over the years note that their diagnostic journey can take 5 years on average.
Can you talk about the treatment and research landscape surrounding this disease?
Patients with Niemann-Pick disease are treated symptomatically. As these symptoms appear, they are treated and followed and tracked. In developed countries, patients tend to have teams of doctors working with them.
There is one approved drug in Europe (not the United States) called miglustat (Zavesca), a substrate reduction therapy. In the US, it’s approved for Gauscher’s disease — and so, patients will often use it if they have access to it or if their insurance will cover it.
That drug works on neurologic symptom but does not help every patient. And then there are some side effects that some patients don’t tolerate well. So, not every patient that has access to it uses that drug for long-term.
And so, there really is a need for more therapeutic interventions in this space.
In terms of clinical research, our company is working on Trappsol® Cyclo as our product. The drug has a particular affinity for cholesterol. It captures this unesterified cholesterol in the core of the molecule.
We’ve completed a phase 1 trial, a phase 2 trial, and we have launched and are enrolling our phase 3 trial now. And we’ve started in the United States.
The drug is given intravenously and is a relatively long-infusion with 6.5 hours.
Our phase 1 trial showed a very favorable safety profile and showed that our drug removes cholesterol from our cells. Our phase 2 study showed very promising signals of efficacy, including neurologic.
We want to see options for patients — this a heterogenous disease. We want patients to have multiple options.
What resources are there for these patients?
There are organized groups who work to advocate on behalf of NPC families. In the United States, we work very closely with the National Niemann-Pick Foundation (NNPDF). In the United Kingdom, there’s a very well-organized group: NPUK.
And there are others around the world. There’s an umbrella organization called the International Niemann-Pick Disease Alliance, which has the national organizations as their members. They help these advocacy organizations come up to speed, and they share best practices.
We work with all of them and talk about our trial. We want to be sure the patients understand what opportunities are available to them.
[Quotations edited for clarity.]
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