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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multisystemic Smooth Muscle Dysfunction Syndrome
• Intervention / Treatment: Drug: Kuvan (Sapropterine)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open label Intervention; Participant will receive KUVAN® (sapropterin dihydrochloride) 100 mg Powder Packets once daily.	Drug: Kuvan (Sapropterine); Sapropterine 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Crossing of percentile of growth	2 years
Increase of mean diastolic blood pressure by more than 8 mmHg	2 years
Absence of cerebral vascular complications	2 years
Absence of progression of cerebral vascular disease	2 years

Collaborators and Investigators

• Sponsor: Gregor Andelfinger

Publications and helpful links

General Publications

• Krishnan V, Rahman A, Das S, Weil M, Altman S, Shamber C, Fong CT, Goldstein AM, Lindsay ME, Musolino P. A novel drug Sapropterin (Kuvan) ameliorates the disease phenotype in a mouse model of multisystem smooth muscle dysfunction syndrome. Child Neurology Society Meeting Vancouver. 2023.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Kuvan; multisystemic smooth muscle dysfunction syndrome; MSMDS; Sapropterine
• Additional Relevant MeSH Terms: sapropterin
• Other Study ID Numbers: SPS-MSMDS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No