A Single Patient Study of Sapropterin for Multisystem Smooth Muscle Dysfunction Syndrome

A Single Patient Study (SPS) of Sapropterin for Multisystem Smooth Muscle Dysfunction Syndrome (MSMDS).

There is currently no approved treatment for multisystem smooth muscle dysfunction syndrome (MSMDS). This single-patient study is the first to be conducted in a child with MSMDS in Canada and was designed to provide the child with access to sapropterin treatment. The molecule we will be using, sapropterin (Kuvan), is already approved and available for other indications. This disease is caused by a genetic variant in the ACTA2 gene. This variant prevents the small units of actin fibers, which are the molecular motors of the smooth muscle cell, from assembling correctly. The goal is to gather data so that the drug can be approved for this indication and thus treat the patient.

We plan to repurpose sapropteride, a synthetic form of tetrahydrobiopterin (BH4), an essential cofactor of phenylalanine hydroxylase (PAH). Sapropteride is already approved in Canada for the treatment of phenylketonuria (PKU) and has shown promise as an agent against multisystem smooth muscle dysfunction syndrome (MSMS) in an animal model. No clinical trials are currently underway with sapropteride for MSMS.

Inclusion Criteria:

• Patients with the following molecularly confirmed genotype: ACTA2 c.536G>A, p.Arg179His
• Aged 1 month to 18 years

Exclusion Criteria:

• Previous exposure to Kuvan®, Biopten®, or any preparation of tetrahydrobiopterin for greater
• Known hypersensitivity to Kuvan® or its excipients
• Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin
• Current use of medications that are known to affect nitric oxide synthesis, metabolism or action
• Current use of experimental/other investigational or unregistered drugs that may affect the study outcomes
• Inability to comply with study procedures
• Concurrent disease or condition that would interfere with study participation or increase the risk for adverse events, including stroke, renal or hepatic failure
• Other significant disease that in the Investigator's opinion would exclude the subject from the trial
• Any condition that, in the view of the Principal Investigator renders the subject at high risk for failure to comply with treatment or to complete the study