Archive news 2020 - International Mito Patients

What is the CureMILS Project?

The project - full name 'CureMILS - A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome' - is an exciting research project which aims to develop therapies for mitochondrial DNA-associated Leigh syndrome (MILS).

Professor Prigione explains what the project involves in this 3 minute video.

IMP is a partner in the project, which is part of the European Joint Programme on Rare Diseases.

Click to watch.

Read more about the project.

CureMILS - A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome

This exciting research project aims to develop therapies for mitochondrial DNA-associated Leigh syndrome (MILS).

IMP is a partner in the project, which is part of the European Joint Programme on Rare Diseases.

Click to watch Professor Prigione explain the CureMILS project (3 minutes).

March 2021

Watch Professor Alessandro Prigione provide an update on the CureMILS project.

February 2021

Research Study into Leigh Syndrome Receives Large EU Grant

IMP is delighted to be a participant in the 'CureMILS - A reprogramming-based strategy for drug repositioning in patients with mitochondrial DNA-associated Leigh syndrome'. In February 2021, the programme received a grant from INSERM as part of the European Joint Programme on Rare Diseases.

As part of the grant, IMP will contribute its expertise of the burden of living with Leigh syndrome or having a child suffering from Leigh syndrome. IMP may also help identify patients to be involved in the project, as well as organise a workshop at the end of the project to share results and discuss implementation of the study results. The award budget for IMP is 50,000 euros as part of the 3 year project. Dr Philip Yeske, IMP Board Member and UMDF's Science and Alliance Officer, will serve as the main point of contact for the project. Read more about the project below.

Click to watch Professor Prigione talk about securing the grant for the CureMILS project (2 minutes).

Neural Progenitor Cells

New European research consortium to study rare disease in children

Prof. Dr. Alessandro Prigione at the University Hospital Düsseldorf / Heinrich Heine University Düsseldorf coordinates the consortium with partners from seven countries

The Joint European Program for Rare Diseases (EJP-RD), established within the European Research Framework Program Horizon 2020, brings together over 130 institutions from 35 countries. It has focused on preclinical research to develop effective therapies for rare diseases. It will now fund a new international consortium called CureMILS with a total of 2.4 million Euros. The research project aims to develop therapies for mitochondrial DNA-associated Leigh syndrome (MILS).

MILS is a rare genetic neurological disorder of children that results from a disorder of mitochondrial metabolism. Currently, there are no cure or effective treatments for this severe disease, that leads to degeneration and death of brain regions. The life expectancy of affected children is only a few years.

One of the aspects that hinders the search for new therapies is the lack of effective disease models for MILS. To develop such models, CureMILS will use cellular reprogramming technology. It allows neuronal cells to be generated from patients' own skin cells. The reprogrammed neuronal cells will be used to test compounds using high-throughput screening. The identified compounds will be evaluated using three-dimensional brain organoids, organ structures that can be generated in the laboratory using stem cells. They can be obtained from skin cells of MILS-patients.

The consortium is coordinated by Prof. Dr. Alessandro Prigione at the Department of General Pediatrics, Neonatology and Pediatric Cardiology at the University Hospital Düsseldorf (UKD). The consortium will involve seven other partners from seven European countries: Germany (UKD and Fraunhofer IME Hamburg), Austria (University of Innsbruck), the Netherlands (Radboudumc Nijmegen), Finland (University of Helsinki), Poland (Institute of Genetics and Animal Biotechnology, Jastrzebiec), Italy (University of Verona), and Luxembourg (University of Luxembourg). The consortium is being conducted in collaboration with International Mito Patients (IMP), a network of national organizations on mitochondrial diseases. Other participants are cooperation partners from Germany, the Netherlands and Italy, Oroboros Instruments GmbH and the German Network for Mitochondrial Diseases (mitoNET).

Further Information

EJP-RD link: EJP RD – European Joint Programme on Rare Diseases (ejprarediseases.org)

EJP-RD funded Projects: https://www.ejprarediseases.org/index.php/funded-projects-2020/

CureMILS website hosted by Oroboros Instruments: https://wiki.oroboros.at/index.php/CureMILS

Homepage of Prigione Lab: www.uniklinik-duesseldorf.de/prigione-labor

New LHON Webpage & German Translation of Brochure

IMP is pleased to publish a new webpage dedicated to LHON, as well as the German translation of the LHON Brochure. Thank you to Lennart Sass at LHON Deutschland e.V. for the translation. The brochure, originally published in late 2020, is also available in Italian and English.

LHON is a type of mitochondrial disease, which causes acute vision loss. The onset is generally in adolescence or early adulthood. Vision loss starts with no warning and frequently progresses very quickly from one eye to both.

There are many LHON patient organisations around the world as well as national mito patient organisations that support people with LHON.

Visit the LHON page.

Last Chance to Join International Mito COVID-19 Data Study

Are you a mito patient and have had COVID-19? Your experience could help other mito patients.

Join this important study by contacting Dr Chiara Pizzamiglio (This email address is being protected from spambots. You need JavaScript enabled to view it.) and Dr Robert Pitceathly (This email address is being protected from spambots. You need JavaScript enabled to view it.).

Recruitment will finish by the end of March.

What is this study about?

The Highly Specialised Service for Rare Mitochondrial Disorders in London has created a database to register children and adults with mitochondrial disease who contract "Coronavirus Disease 2019" (COVID-19). The reason for doing this is to understand how COVID-19 affects people with mitochondrial disease, and whether the response is different to people without mitochondrial disease. It is hoped that this knowledge will improve the treatment of COVID-19 in people with mitochondrial disease. Details concerning your mitochondrial disease and the symptoms and treatment received for COVID-19 are entered into the database, but no identifiable information is included (i.e., the data is anonymised). The research team might contact your mitochondrial specialist to confirm certain details surrounding your diagnosis and relevant medical professionals involved in your COVID-19 treatment. This is particularly relevant if you were admitted to hospital with COVID-19.

Who can take part?

The study is aimed at anyone (children or adults) with strongly suspected or genetically confirmed mitochondrial disease with either suspected or confirmed COVID-19. From all countries in the world. We would encourage the mitochondrial community to report all cases of COVID-19 irrespective of the symptoms and severity. This means people without symptoms, in whom COVID-19 was detected through routine screening, and those with typical (fever, cough and/or loss of smell/taste) or atypical symptoms would be included. We would also like to include both people who stayed at home and those that required admission to hospital. Finally, we would like to include people who had both a positive COVID-19 test (swab or blood test) and those with symptoms suggestive of COVID-19, even if they had a negative COVID-19 test.

What is involved in taking part?

The study will help to develop a database of individuals with mitochondrial diseases and confirmed or suspected COVID-19. The database is anonymous, so the name or any other personal details (for example, date of birth) will not be collected. To participate, please contact Dr Chiara Pizzamiglio (This email address is being protected from spambots. You need JavaScript enabled to view it.) and Dr Robert Pitceathly (This email address is being protected from spambots. You need JavaScript enabled to view it.) and they will contact you to obtain further information concerning your diagnosis and COVID-19 experience. The time required to obtain all the information is approximately 15-20 minutes. Please note that you will not be provided with clinical advice on the management of COVID-19.

Are there any risks?

There are no risks in participating in the study.

Who will benefit?

The research team hopes to understand how COVID-19 affects people with mitochondrial disease to improve knowledge of the course and improve management of the infection in people with mitochondrial disease.

How do I find out more?

If you would like to know more about the study or would like to participate please contact Dr Chiara Pizzamiglio (This email address is being protected from spambots. You need JavaScript enabled to view it.) and Dr Robert Pitceathly (This email address is being protected from spambots. You need JavaScript enabled to view it.).

LHON and IMP

IMP offers support to everyone affected by every type of mitochondrial disease (mito). There are many types of mito, affecting patients in many different ways.

LHON is a type of mito, which causes vision loss. There are national LHON patient organisations around the world who support those affected locally. IMP welcomes these organisations to join forces with IMP, and its other members, to create a louder voice for all.

IMP works closely with LHON patient advocate, Paula Morandi.

Find out more about becoming a member.

WHAT IS LHON?

LHON stands for Leber’s Hereditary Optic Neuropathy or Leber Optic Atrophy.

LHON is a mitochondrial disease (mito) caused by a change in the function of mitochondria, which are the energy producing organelles.

In LHON the optic nerve is particularly vulnerable to mitochondrial defects because of the high-energy requirements and the need to keep the retina transparent to light.

LHON causes acute vision loss, occurring most commonly in adolescents or young adults. It is caused by mitochondrial DNA mutations and can only be inherited from the maternal line, unlike nuclear DNA mutations. The mother can be unaware of transmitting the risk for such a disease as she frequently carries the mutation without being affected. There are three mitochondrial DNA mutations which are responsible for the majority of LHON cases (about 90%), however, more rare mutations have been discovered that also cause central vision loss – a typical hallmark of LHON.

LHON has a prevalence of 1/25.000 to 1/50.000 and it is more frequent in males.

WHAT ARE THE SYMPTOMS?

Patients typically notice vision loss in one eye, as if a small part of the picture had been cut out in the center. This usually bright spot, expands towards the edges leaving a small peripheral residue. At this point the other eye also starts to lose its central vision. This central hole is called “scotoma” and it may have different shapes, from a bright ball to a star. In the majority of cases the patient begins losing vision in the second eye a few weeks or months after initial onset, but a bilateral involvement can be also manifest since the beginning of the disease. Loss of vision in the second eye can lead to blindness, as the brain is not used to employing the peripheral visual residue.

The peripheral visual residue gives a low kind of vision, similar to a monitor where the pixels are no longer working and the image is composed of lots of little bright grey and white dots, this is sometimes known as “chess board vision”.

HOW CAN OPHTHALMOLOGISTS HELP?

Unfortunately, LHON is often mistaken for Optic Neuritis and therefore Multiple Sclerosis, an ischemic lesion or even a brain tumor. It is important that eye doctors ask patients whether there is any family history of vision loss along the maternal line, and if it is accompanied by pain in the eye region, which is usually absent in LHON. During an eye examination in the acute phase the back of the patient’s eye in some cases may show typical signs of the disease (optic disc pseudoedema, hyperemia and micro- angiopathy) but in other cases it may look completely normal. Further investigations such as Optical Coherence Tomography (OCT), visual fields and electrophysiology (Pattern visual evoked potentials and Pattern Electroretinogram) may help to gain an accurate diagnosis. The OCT is the most reliable examination for quantitatively measuring the degree of damage of the optic nerve and its progression.

WHAT IS IT LIKE TO HAVE LHON?

Some patients describe it as being constantly blinded by the sun, day and night. LHON patients are unable to recognize faces, read books or street signs because of the constant bright light or large grey blind spot.

LHON, which can lead to legal blindness, is not characterized as the type of visual impairment mainly manifested in low light situations. Therefore, it must not be mistaken for Leber’s Congenital Amaurosis, which is also called “darkness disease”, a retinopathy not caused by a dysfunction of the mitochondrial metabolism.

Voice synthesizers and other technology on smart phones and computers can significantly help legally blind people work, study and complete everyday activities.

To watch a video of real LHON patients describe the impact on their lives, and that of their families, please click here

IS THERE A CURE?

Currently, there is no definitive cure or way to stop the progression of the disease. High dosages of antioxidants, such as Idebenone, can help to stabilize the course of the disease and, if diagnosed early, can significantly lower the damage in both eyes, thus favouring vision improvement. Research into gene therapy, and other possible therapies is taking place around the world, with the hope that treatments and cures will be soon available, as currently under development.

As a means of prevention, it is strongly recommended to avoid smoking, as well as alcohol.

The above content has been revised by:

Dr Piero Barboni Neuro - ophthalmologist, IRCCS Ospedale San Raffaele of Milan

Prof. Valerio Carelli, Neurologist, IRCCS Istituto delle Scienze Neurologiche di Bologna, University of Bologna

Dr Anna Maria De Negri Neuro - ophthalmologist, Azienda Ospedaliera San Camillo Forlanini of Rome

Dr Chiara La Morgia Neurologist, IRCCS Istituto delle Scienze Neurologiche di Bologna, University of Bologna

LHON AWARENESS DAY

The LHON Awareness Day is organized by IMP, to raise awareness and understanding about Leber’s Hereditary Optic Neuropathy. LHON Awareness Day falls on 19 September every year, as part of World Mitochondrial Disease Week.

The LON Awareness Day logo represents a rosemary branch, an evergreen plant, which grows around the world and has many beneficial health effects. Rosemary is the symbol of memory and energy, and its shape is similar to a mitochondrion. The color green represents mitochondrial diseases and so, whenever you see a rosemary branch, think of LHON and hope for a cure.

RESOURCES

Please click on the images to download and share these brochures to inform others about LHON. The brochures are available in English, Italian, German and Portuguese.