Rare paediatric heart disease

Restoring relaxation to the stiff heart

Lusitro is developing the C27 peptide, based on the research of Prof. Jian-Ping Jin (University of Illinois Chicago), as a potential treatment for children with TNNI3-related restrictive cardiomyopathy. Our goal is a therapy that reaches patients and stays affordable.

Read our story How C27 works

Lusitropy (from Greek lusis, loosening): the ability of the heart muscle to relax between beats. It is exactly this that fails in restrictive cardiomyopathy, and exactly this that C27 aims to restore.

Our story

Isis and Seppe

Isis and Seppe are two Dutch children living with restrictive cardiomyopathy (RCM) caused by a mutation in the TNNI3 gene. In RCM the heart muscle becomes stiff and cannot relax properly between beats, so the heart struggles to fill with blood. Today there is no treatment that addresses the cause of the disease.

Mark Hage, Isis's father, began searching for a way forward. That search led to the work of Prof. Jian-Ping Jin, who has spent many years studying cardiac troponin I, the protein affected by the mutation, and who developed a peptide that targets the underlying mechanism.

To carry this work from the laboratory towards patients, Mark founded Lusitro B.V. Isis and Seppe come first. But the same mechanism may also be relevant for other forms of diastolic heart failure, which affect many more people.

[Photo of Isis]

[Photo of Seppe]

Isis and Seppe. Photos shared with the consent of both families.

The science

C27: a peptide from the heart's own protein

In TNNI3-related RCM the heart's contractile filaments are too sensitive to calcium, so they do not switch off fully between beats. C27 is a short peptide derived from the heart's own troponin I that is designed to restore that switch.

01 · ORIGIN

Based on a natural human protein

C27 corresponds to amino acids 184–210 of cardiac troponin I, a regulatory region that binds tropomyosin in a calcium-dependent way.

02 · MECHANISM

Selective lusitropy

In laboratory studies from the Jin group, C27 bound tropomyosin, reduced the calcium sensitivity of the contractile filaments and promoted relaxation. These are preclinical findings in experimental models.

03 · PATIENT MODELS

Patient-specific heart models under development

Heart muscle cells are being grown from stem cells of Isis and Seppe (iPSC-derived cardiomyocytes). A key scientific challenge is maturing these cells far enough to express the adult form of troponin I, so that the effect of C27 can be studied reliably. Efficacy in these models has not yet been shown.

C27 is an investigational compound. It has not been tested in patients and is not an approved treatment.

Key publications

Wong S, Feng H-Z, Jin J-P. The evolutionarily conserved C-terminal peptide of troponin I is an independently configured regulatory structure to function as a myofilament Ca²⁺-desensitizer. J Mol Cell Cardiol 2019;136:42–52. doi:10.1016/j.yjmcc.2019.09.002
Hornos F, … Jin J-P. The muscle-relaxing C-terminal peptide from troponin I populates a nascent helix, facilitating binding to tropomyosin with a potent therapeutic effect. J Biol Chem 2021. doi:10.1074/jbc.RA120.016012
Related mechanism (N-terminal truncation of troponin I): Feng H-Z, Huang X, Jin J-P. N-terminal truncated cardiac troponin I enhances Frank-Starling response by increasing myofilament sensitivity to resting tension. J Gen Physiol 2023. doi:10.1085/jgp.202012821

Roadmap

From the lab towards the first patients

We are building the shortest responsible route to treatment: careful enough to protect patients, focused enough to matter in time for these children.

1
Patient models and efficacy Now
Mature patient-specific heart cells and test whether C27 improves relaxation in them. This is the first go/no-go point.
2
Peptide, manufacturing and safety Next
Define the drug candidate and its formulation, produce it to pharmaceutical quality (CMC/GMP), and run preclinical toxicology and pharmacokinetic studies.
3
First-in-human microdosing Next
A microdose imaging (PET) study shows how C27 distributes in the body and whether it reaches the heart. It does not by itself show that a therapeutic dose is safe or effective.
4
Regulatory review and first patients Goal
With a proportionate safety and dosing package, and only after review by the competent authorities and ethics committees, a named-patient route for Isis and Seppe in close consultation with their cardiologists.

Collaboration

Working with leading research partners

Lusitro connects the original invention with the academic, clinical and regulatory expertise needed to develop it. The status of each relationship is stated below.

Prof. Jian-Ping Jin · University of Illinois ChicagoInventor of the C27 technology. Lusitro is in licensing discussions with the UIC technology transfer office, under a confidentiality agreement.Licensing in discussion

UMC UtrechtDevelopment of patient-specific iPSC heart cell models from Isis and Seppe.Ongoing research

Amsterdam UMCMolecular imaging and cardiac muscle research for a joint research proposal.Proposal in preparation

Netherlands Heart Institute · Dutch Heart FoundationExploratory discussions on a public-private partnership within the FORESIGHT programme.Exploratory

No funding commitment or endorsement by these institutions is implied unless stated.

What Lusitro does

An active translational R&D partner

Lusitro B.V. holds the industrial role in the programme: it aims to license the C27 technology and to take responsibility for its further development towards patients.

Development strategy and regulatory architecture for a proportionate route to the first patients.
Quantitative translational modelling: pharmacokinetic/pharmacodynamic modelling and dose justification.
Data analysis and integration across cell models, imaging and preclinical studies.
Coordination of academic partners, contract research organisations and funders.

Founder Mark Hage brings a background in high-tech systems R&D, test design and data-driven engineering.

Our mission

An affordable medicine

Treatments for rare diseases are often priced out of reach. Lusitro was started by a parent, not by investors, and we intend to keep it that way in spirit: our aim is a therapy that is not only effective, but also affordable for the families who need it.

A peptide based on a natural human protein can be manufactured at reasonable cost. If C27 proves effective, we want that advantage to reach patients.

Support this work

What your support makes possible

Maturing and validating the patient-specific heart cell models
Producing the C27 peptide for research and preclinical studies
Biodistribution and safety studies
Preparing the first clinical study and the regulatory dossier

Donations are made through Stichting Tikkertje, the foundation that funds research towards a treatment for Isis and Seppe.

Are you a foundation, patient organisation or research partner? We would welcome a conversation.

Donate via Stichting Tikkertje mark@lusitro.com