Delivering tomorrow's treatments for today's patients

Leigh Syndrome International Consortium Grant Cycle 2021

Funding awarded to five recipients

The Leigh Syndrome International Consortium is delighted to announce it will grant a total of $150,000 USD to five research teams that are actively working toward improving diagnosis, developing treatments and optimizing clinical care for Leigh syndrome patients.

The Recipients Are:

Institution:    University of Padova, Italy

Applicant:     Massimo Zeviani

Project:         Gene therapy in mouse models of Leigh syndrome

Award:          50,000 USD

Description: This project is focused on replacing the crippled nuclear gene with a normal nuclear gene copy using a well-established mouse model in studying Leigh syndrome (NDUFS4). This gene encodes a subunit of complex I (CI), causing fatal mouse (and human) Leigh syndrome. The project entailed injecting a normal human NDUFS4 gene in baby mice at birth. This treatment let the mice grow normally. The team examined the first animal at 6 months, which was in good health, with normal body weight, and no neurological impairment. They found restoration of normal CI activity in a structurally normal brain. The team proposes to follow the treated mice and analyze them post-mortem. To test whether this therapy can correct other causes of LS, they will treat two additional LS models already available in mice. If successful, this project will pave the way for curative gene therapy in LS children.


Institution:    Université Grenoble-Alpes, France

Applicant:     Michael Decressac

Project:         Combining gene replacement and focused ultrasound to treat Leigh syndrome

Award:          30,000 USD

Description: The objective of the project is to use a virus, as a therapeutic tool, previously used to cure other diseases in patients and to help it pass the blood brain barrier using ultrasounds (quite similar to those used for echography). These ultrasounds were proven to be safe in humans and allowed the passage of viruses from the blood to the brain. However, this method has never been tested in the context of Leigh syndrome or any diseases caused by mitochondrial defect, and the study intends to fill this gap. The team will test this method in a mouse model of Leigh syndrome examining its short and long-term effects. If successful, this method could be transferred to the clinic and may provide a cure for patients with Leigh syndrome.


Institution:    University of Iowa/Heinrich Heine University (HHU)

Applicant:     Dao-Fu Dai/Alessandro Prigione (2019 LSIC Grant Awardees)

Project:         Induced pluripotent stem cells (iPSC)-driven drug repositioning for Leigh syndrome

Award:          40,000 USD

Description: The team previously established an effective drug discovery platform for Leigh syndrome using neural cells differentiated from induced pluripotent stem cells (iPSCs) that were derived from patients with Leigh syndrome. The aim of this grant is to determine whether the same beneficial effects can be observed for other gene mutations that cause Leigh syndrome and to extend this approach by screening a larger library of FDA-approved compounds. To accomplish this, the project will combine the iPSC-driven drug discovery approach with functional validations in a mouse model of Leigh syndrome. The project has already proven to be effective and therefore has the potential to identify effective drugs that can be quickly repositioned to treat patients currently affected by Leigh syndrome.


Institution:    North-West University, South Africa

Applicant:     Roan Louw

Project:         Using a variety of pre-clinical disease models to identify novel drug candidates for the treatment of Leigh syndrome

Award:          8,000 USD

Description: The team’s previous work on the Ndufs4 mouse, an excellent animal model mimicking Leigh syndrome, identified several promising therapeutic targets that can potentially be used to treat Leigh syndrome. This project proposes to build onto this existing work and data to test therapeutic candidates. The project will use different models across multiple, distinct species in the drug discovery processes, as this approach was shown to greatly increase the rigor and translatability of pre-clinical studies for complex diseases. This study could therefore contribute greatly towards identifying novel therapeutic approaches for the treatment of Leigh syndrome.


Institution:    University of Davis California

Applicant:     Gino Cortopassi (2019 LSIC Grant Awardee)

Project:         Safety, Efficacy and Mechanism of a Nicotinamidated Fumarate for Leigh syndrome

Award:          22,000 USD

Description:   This project proposes to use Nicotinamidated Monomethyl Fumarate (NMF), a new molecule which improves function and lifespan in Leigh syndrome model mice & other mice with mitochondrial disease. This NMF molecule is patented. However, to further ‘de-risk’ the molecule for pharma to invest in clinical trials for Leigh syndrome with NMF, the team proposes to carry out a safety and efficacy experiment and a drug targets experiment to determine whether the drug is hitting specific targets in the brain to elicit protection in Leigh syndrome context. In addition to funding research grants, the Consortium is leading a Natural History Study to collect, analyze and share de-identified natural history data with partners around the world with the goal of facilitating clinical trials on Leigh syndrome.