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Clinical Trial Begins New Treatment of For Niemann-Pick Disease, a Rare, Fatal Neurological Disorder


Target Health has been directly involved with the approval of 3 drugs for the treatment of orphan diseases and has received 11 Orphan Drug Designation for our clients in the following designations:


1.            Gaucher Disease – (NDA Approved 2012

2.            Hereditary angioedema – NDA Approved (2011)

3.            Debridement of 3rd degree burns in hospitalized patients (EMA Approval 2012)

4.            Scleroderma

5.            Osteonecrosis of the jaw

6.            Alagille Syndrome

7.            Burn progression in hospitalized patients

8.            Caries prevention, head and neck cancer

9.            Cushing’s syndrome secondary to ectopic ACTH secretion

10.          Edema-related effects in hospitalized patients with 3rd degree burns

11.          Growth Hormone


Niemann-Pick type C (NPC) is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. NPC strikes an estimated 1:150,000 people. Approximately 50% of cases present before 10 years of age, but manifestations may first be recognized as late as the sixth decade. NPC is biochemically, genetically and clinically distinct from Niemann-Pick Types A or and B. In Types A & B, there is complete or partial deficiency of an enzyme called acid sphingomyelinase. In NPC, the protein product of the major mutated gene NPC1 is not an enzyme but appears to function as a transporter in the endosomal-lysosomal system, which moves large water-insoluble molecules through the cell. The protein coded by the NPC2 gene more closely resembles an enzyme structurally but seems to act in cooperation with the NPC1 protein in transporting molecules in the cell. The disruption of this transport system results in the accumulation of cholesterol and glycolipids in lysosomes. In NPC, large amounts of free or unesterfied cholesterol accumulates in lysosomes, and leads to relative deficiency of this molecule in multiple membranes and for steroid synthesis. The accumulation of glycosphingolipids in the nervous system has been linked to structural changes, namely ectopic dendritogenesis and meganeurite formation, and has been targeted therapeutically. Several theories have attempted to link the accumulation of cholesterol and glycolipids in the lysosomes with the malfunction of the NPC-1 protein. No FDA-approved therapies are available to treat NPC.


In 2009, the NIH Therapeutics for Rare and Neglected Diseases (TRND) program, selected NPC cyclodextrin as one of its initial pilot projects to repurpose cyclodextrin from its conventional use as an ingredient in other drugs to a therapeutic for this rare disorder. TRND supported animal toxicology studies to evaluate the safety of cyclodextrin and all necessary regulatory efforts and also supported the development of an NPC biomarker. The biomarker test detects in the blood a modified cholesterol molecule specific to neuronal cells in the brain that would increase as a result of treatment with cyclodextrin. TRND researchers and collaborators submitted the data in an Investigational New Drug (IND) application, and FDA has now agreed that there are sufficient data to start a Phase I clinical trial.


The NPC Phase I clinical trial will test multiple doses of cyclodextrin in nine patients. The team also is conducting a natural history study of NPC to collect health information from patients to understand how the disease develops. The natural history study is critical to understanding the clinical significance of a treatment for NPC patients. The goal of the Phase I clinical trial is to determine a safe dose of cyclodextrin that will support an expanded Phase II trial to begin to evaluate the effectiveness of the drug.


The NPC clinical trial is the fourth TRND project to advance to human clinical trials in the last 15 months. The three other clinical trials are evaluating treatments for sickle cell disease, chronic lymphocytic leukemia and hereditary inclusion body myopathy. TRND has a portfolio of 14 projects, which focus on rare and neglected tropical diseases.


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