International Research Group Works to Increase Knowledge, Awareness of Neurotransmitter Disorders

Since its founding in 2013, the International Working Group on Neurotransmitter related Disorders (iNTD) has been building a network and patient registry aimed at promoting knowledge and awareness among clinicians on rare neurotransmitter disorders, including aromatic l-amino acid decarboxylase (AADC) deficiency.

Over the past several years, the collaboration has expanded its partnership network and patient registry database, published consensus guidelines for AADC patients, reported clinical outcomes of pregnant women with tetrahydrobiopterin deficiencies, and performed a comprehensive review on neurotransmitter disorders.

The group is now planning to develop a series of consensus guidelines focused on the diagnosis and treatment of these disorders. The guidelines will be based on evidence gathered from the patient registry, and on systematic literature reviews for patients with the most frequent neurotransmitter disorders.

In addition, iNTD is working on developing a Parkinsonism-Dystonia–Rating scale to promote the clinical examination of movement disorders in children, and provide a reliable and comparable assessment tool during patients’ follow-ups.

The group published its first study, “The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders,” in 2016 in the journal Molecular Genetics and Metabolism Reports.

Neurotransmitters are the chemical substances that allow communication between nerve cells at specific cell-cell junctions, called synapses. When genetic mutations affect the production, breakdown, or transport of neurotransmitters, patients may experience neurological impairments that can start at any point in life, from birth to adulthood.

The iNTD was the first international network of rare neurotransmitter disorders and was founded to improve knowledge and raise awareness on these conditions worldwide. In the 2016 study, the researchers outlined the major goals of the organization as well as its future impact for both patients and clinicians.

“In 2013 the initiative ‘International Working Group on Neurotransmitter Related Disorders (iNTD)’ was founded by three medical experts from the University Hospital Heidelberg (Germany), the Hospital Sant Joan de Déu in Barcelona (Spain) and the Great Ormond Street Hospital in London (United Kingdom) with the aim to foster scientific and clinical networking on an international level and, ultimately, to promote health care for patients with neurotransmitter related disorders,” the researchers said.

At the time, the initiative had recruited 43 project partners from 24 countries. It had also created an online patient registry for gathering long-term clinical data on disease progression, diagnosis, treatment, and patients’ quality of life. In just six months, from the beginning of data collection in January 2015 until June 2015, 95 patients with a confirmed diagnosis of neurotransmitter disorder had been registered in the database.

Initially, patients with AADC deficiency — a rare disease caused by a deficiency in the AADC enzyme, which is necessary for the production of the neurotransmitters dopamine and serotonin — were the most represented in the registry at 25%, followed by those with 6-Pyruvoyl-tetrahydropterin synthase deficiency at 23%, and autosomal dominant GTP-cyclohydrolase deficiency at 13%.

“The predominance of AADC deficiency is partly explained by the support of the AADC parent organization (AADC Research Trust) which promoted the study within their membership,” the investigators said at that time.

Since then, the iNTD has expanded its partnerships to 34 countries and has continued to grow its database, which now has 387 registered patients.

“The first guidelines developed by iNTD were for the diagnosis and treatment of AADC deficiency. The development of evidence based guidelines for inborn errors [genetic diseases] of BH₄ [tetrahydrobiopterin] disorders will follow in near future as the next iNTD guideline,” the researchers said in the study. “In the future iNTD aims to further improve the awareness and knowledge on rare neurotransmitter related disorders by providing clinical and scientific information to patients and health care professionals. The long term focus will be on the evaluation of disease natural history, specifically in the context of upcoming new treatment options.”