Care guidelines for PLAN are now in progress

Care guidelines for PLAN are now in progress

Translation of an English article by Patricia Wood

Thanks to the support of four organisations funding the project, consensus guidelines for the treatment and care of a form of NBIA known as PLAN or PLA2G6-associated neurodegeneration are now in the works.

This is the third NBIA condition for which researchers have developed best practices. The other two are more common forms of NBIA, PKAN, and BPAN. PLAN encompasses a wide range of symptoms, and depending on the age of the sufferers and their symptoms, they can be classified into one of three subtypes: INAD, aNAD, or PLA2G6-related dystonia-parkinsonism.

Four organisations have joined forces to support "Best Practices in the Care and Treatment of People with PLAN". In addition to the NBIA Disorders Association, these are the INADcure Foundation, a U.S.-based nonprofit organization that advocates for people with INAD and other subtypes of PLAN, as well as NBIA's sister organizations, Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) in Italy and Hoffnungsbaum e.V. in Germany.

Image: Dr. Susan Hayflick from OHSU

Dr. Susan Hayflick of OHSU is the lead researcher, collaborating with her colleagues Dr. Jennifer Wilson as lead author and Allison Gregory, MS, as principal investigator. This group has also developed the care guidelines for PKAN and BPAN.

The main objective of this project is to advise clinicians on the best and most acceptable course of action in the diagnosis, care or treatment of PLAN and its three subtypes. Since INAD is the most common form of PLAN, a larger portion of the guideline is likely to focus on this subtype.

Good practices will be covered in the following areas: diagnostic assessment, initial treatment, pharmacological and surgical care, observation for disease complications, emergency management, educational support, nutrition, psychosocial support and all other areas mentioned by the participants.

Other leading PLAN experts are also invited to contribute, as well as selected parents, carers and the funding patient organisations. Members of the larger patient and family community and other patient organisations are invited to review and comment on the final draft of the guideline within two weeks.

The project will take about 12 months to submit a draft for publication. The total cost is $50,308, which is made up of personnel costs that cover the time and work of the project team with their expertise, project management, and coordination. Other costs include publication fees for free public access to the paper and travel costs for presenting the results at two meetings within one year of publication.

Translated from: NBIA Disorders Association December 2022 Newsletter, p. 4/5:

Translated with (free version)

INAD gene therapy is one step closer

INAD gene therapy is one step closer

Abridged translation of an English article by Patricia Wood

Work on a gene therapy for infantile neuroaxonal dystrophy, called INAD, got a big boost in October when a London-based biotech firm announced its intention to help bring the therapy to market.

London-based Bloomsbury Genetic Therapies Limited, known as Bloomsbury, is looking to advance its efforts with the help of £5 million in seed funding from the UCL Technology Fund. Bloomsbury is working on a gene therapy based on adeno-associated viruses (AAV) called BGT-INAD to treat INAD.

INAD is a form of PLA2G6-associated neurodegeneration, or PLAN, that usually occurs between 6 months and 3 years of age and progresses rapidly. Many affected children do not survive their first decade of life. (...)

Bloomsbury benefits from the expertise of its academic scientists in gene therapy and rare diseases, including Professors Manju Kurian and Ahad Rahim of University College London. Kurian and Rahim have been working on a gene therapy treatment for INAD for eight years. The NBIA Disorders Association awarded researchers a $150,000 grant in 2014 to begin work. This was followed by £655,000 from the UK's Medical Research Council.

Image: Researchers from University College London at the 8th International NBIA Symposium in October 2022, where they presented their work.
L-R: Professor Ahad Rahim, Dr. Apostolos Papandreou, Dr. Audrey so, Professor Manju Kurian, Dr. Robert Spaull.

At the 8th NBIA International Symposium in Lausanne in October 2022, Rahim presented the promising data for BGT-INAD. Preliminary results show a marked improvement in survival and behavioral parameters in mice treated with BGT-INAD.

Dr Audrey so, who is part of Professor Kurian's research group at UCL, also gave an update on the preparations for a clinical gene therapy trial with BGT-INAD at the symposium. She said the work was based on an extensive retrospective study of the natural course of the disease with more than 300 INAD patients worldwide. (...)

UCL research has improved the level of knowledge about INAD, including its main features and symptoms. Most importantly, the researchers have developed a meaningful disease-specific rating scale for INAD and discovered potential biomarkers for blood and cerebrospinal fluid. Once fully confirmed, the biomarkers can be used as a measure of outcome in clinical trials, accelerating the development and approval of potential treatments for INAD patients. so said she will continue the development and validation of INAD biomarkers throughout 2023.

Bloomsbury is working with researchers on an accelerated timeline to bring its gene therapy research programs into clinical trials as quickly as possible. Bloomsbury plans to complete the comprehensive efficacy evaluation for BGT-INAD in the INAD mouse model in the first quarter of 2023. Subsequently, the company will focus on the necessary safety tests on animals. It hopes that the accelerated clinical trial design will shorten the time to approval by regulatory agencies such as the European Medicines Agency or the U.S. Food and Drug Administration, allowing it to make the therapy commercially available to treat patients.
Bloomsbury keeps its website up-to-date, so that patients and relatives can inform you about the latest developments. (...)

Full original version of the article and image source in December 2022 newsletter of the NBIA Disorders Association, p. 6/7):
Translated with the support of (free version)

Two MPAN project grants totaling $140,000 awarded

Two MPAN project grants totaling $140,000 awarded

Hoffnungsbaum e.V. in conjunction with three sister organizations in Europe and the US, has awarded two MPAN grants to advance research priorities in the field of mitochondrial membrane protein-associated neurodegeneration (MPAN), which were identified during an expert workshop on MPAN. MPAN is one of the four most common types of the disease group whose generic term is "neurodegeneration with iron storage in the brain".

Dr. Lena F. Burbulla from the Ludwig-Maximilians-Universität in Munich and Dr. Rajnish Bharadwaj from the University of Rochester in New Jersey (USA) each received one-year research grants of $ 70,000 to study MPAN.

The funding was made possible by an international collaboration involving Hoffnungsbaum e.V. NBIA Disorders Association in the USA, Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) in Italy and Stichting Ijzersterk in the Netherlands.

In a workshop at the end of 2020 led by Dr. Francesca Sofia, founder and CEO of Science Compass in Milan, Italy, the researchers jointly discussed a research strategy for MPAN based on existing research data and assessed strengths, challenges and trends in MPAN research to identify a set of scientific priorities. Details can be found here:


Dr. Lena F. Burbulla from the Ludwig-Maximilians-Universität in Munich

Mitochondria, dopamine metabolism and alpha-synuclein

Burbulla's research involves modeling human disease by creating patient-derived cells to discover new mechanisms underlying the pathology of MPAN. To this end, her lab is using induced pluripotent stem cells (iPSCs) derived from skin cells of people with MPAN. Burbulla's team will use these stem cells - which can theoretically be turned into any type of cell in the body - to generate dopaminergic nerve cells, known as neurons, which are known to be affected in the brains of MPAN patients. Dopaminergic neurons produce the neurotransmitter dopamine, a chemical messenger involved in the regulation of body movement, memory, motivation, attention, learning and more.

Mutations in a specific gene, C19orf12, are the only known cause of MPAN. The function of the C19orf12 protein, which is controlled by the gene, is still largely unknown. Using disease modeling approaches, the researchers will investigate the function of the C19orf12 protein in a patient-specific model, in particular how the loss of this protein affects the brain cells. Burbulla and her team want to find out how the loss of C19orf12 function affects the health of the mitochondria in these patients' nerve cells. Mitochondria are the "powerhouses of the cell", producing around 90% of the energy cells need to survive. When mitochondria are damaged, this can have catastrophic consequences for the cell, triggering a series of toxic events that ultimately lead to neuronal death. Since the C19orf12 protein is known to be associated with mitochondria, its loss of function could affect mitochondria and have far-reaching effects on cell health and resilience.

The stem cell model will allow the researchers to compare the MPAN cells with healthy cells and better understand the role of the protein. They will also look beyond the mitochondria for disease-related pathology and investigate possible changes in the processing of the neurotransmitter dopamine in these nerve cells, as well as a protein called alpha-synuclein, which is known to accumulate pathologically in the brains of MPAN patients.

Alpha-synuclein is found at the ends of nerve cells in the synaptic cleft - the area between neurons where neurotransmitters are released to relay messages throughout the body. Abnormally formed or excessively abundant alpha-synuclein leads to aggregation or clumping of proteins and inhibits the normal function of neurons.


Dr. Rajnish Bharadwaj from the University of Rochester in New Jersey (USA)

Knockout flies, lipid metabolism and mitochondrial function

Baharadwaj's research will focus on better understanding the proteins produced by the C19orf12 gene. His team will use models of fruit flies that have been genetically engineered to lack the genes CG3740 and CG11671, which correspond to the C19orf12 gene in humans.

Previous studies by other groups and his ongoing work have shown that the fly models have a shorter life expectancy, movement deficits and a loss of neurons in the brain and retina. This suggests that fruit flies are a promising model for the study of NBIA.

The team's studies also suggest that C19orf12 is a membrane contact site protein that may be involved in communication between organelles, specialized subunits within the cell, such as the endoplasmic reticulum, and lipid droplets (fats). In the cell, the endoplasmic reticulum has the task of producing proteins and is involved in the production and storage of lipids.

The team's aim is to investigate how the C19orf12 protein is involved in lipid metabolism and mitochondrial function. Lipid metabolism is the process of production and breakdown of lipids or fats in cells. The researchers want to uncover this role in the brain and other organs. Both lipid metabolism and mitochondrial function are also involved in other forms of NBIA.

Overall, the creation and study of these disease models and the research that builds on them will improve the understanding of MPAN and pave the way for the much-needed development of treatments.


Source: Article "Two MPAN grants worth $140,000 awarded to further disease insights" in the December 2022 newsletter of the NBIA Disorders Association. Thank you for your kind permission to use the content of the article. Translations with the help of the free version of

October 12, 2022, online lecture: Understanding hereditary developmental disorders better - what you can learn from the natural course of the disease

October 12, 2022, online lecture: Understanding hereditary developmental disorders better - what you can learn from the natural course of the disease

Steffen Syrbe is a paediatric neurologist and professor of paediatric epileptology at Heidelberg University Hospital. He has been working with children with neurodevelopmental disorders for over 15 years. During this time, he has developed a strong interest in the genetic causes of epilepsies and neurological diseases. He has described various neurological genetic diseases and identified new genetic causes. Currently, one focus of his scientific work is the translation of basic research into new therapies.

A better understanding of hereditary developmental disorders – what can be learned from the natural course of the disease, illustrated by the example of BPAN

In order to be able to develop new therapies from the findings of basic research, it is important to understand the natural course of developmental disorders. Only by knowing the natural course of the disease can one assess whether interventions are effective.

You can find an overview of all online lectures here: Online lectures

Prof. Dr. med. Steffen Syrbe

Outpatient clinic for children with epilepsies that are difficult to treat at the Social Paediatric Centre Heidelberg

More info...





Subscribe to our Hoffnungsbaum newsletter!

With our newsletter e-mails you will receive valuable information about NBIA. If you would like to receive additional information on individual NBIA variants or special information for researchers/clinicians in addition to the general newsletter, please click here: Subscribe to additional information

Privacy policy

You have successfully registered!