Research | Dementia Research Network Ireland

Development of Novel Oligogenic ALS Models for Drug Discovery

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease resulting in muscle weakness, paralysis and ultimately death, often within 2-3 years of symptom onset. These symptoms arise due to the loss of motor neurons from the brain and spinal cord. Treatment options are limited and have little impact on halting progression of the disease. This research project is aimed at developing and characterising new models of ALS that can be used to investigate how motor neurons degenerate in people living with ALS.

Analysis of tiRNA and tiRNA-protein Complexes and Development of tiRNAs as Therapeutics and Biomarkers in ALS and Epilepsy.

Project Aim(s): To perform a systematic analysis of tiRNA – protein complexes in ALS and Epilepsy models as well as samples from patients.

Health Professional Fellowship: Environmental and Genetic Epidemiology of Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a terminal neuro-degenerative disorder of adults, typically having rapid progression and involving both motor and cognitive function. ALS exhibits considerable heterogeneity of both symptom profile and progression. Nevertheless, median survival is typically under three years from disease onset. ALS is the most common motor neurone disease in adults, with an incidence of 2 to 3 per 100,000 in Europe.

Sampling and biomarker OPtimization and Harmonization In ALS and other motor neurone diseases (SOPHIA).

Project Aim(s): Development of optimally informative biomarkers for ALS, and establishment of stakeholder agreement regarding their use. This will be achieved by defining, validating and harmonizing optimal methodologies that can be reliably implemented within a pan-European framework program.

European Multidisciplinary ALS Network Identification to cure Motor Neuron Degeneration (Euro-MOTOR).

Project Aim(s): To discover new causative and disease-modifying pathways to pave the way for novel therapies.

Living and dying with Amyotrophic Lateral Sclerosis: A Population based Analysis of Palliative Needs, Services and Outcomes in non-malignant terminal illness.

Project Aim(s): This project aimed to utilize data from the Irish Register and the national ALS service to generate a framework for care for Irish ALS patients based on their clinical phenotype, rate of progression and long term prognosis. The objective was to design, estimate the costs, and measure the benefits of a multifaceted care programme that incorporates the key clinical and prognostic elements of ALS.

A Programme for ALS Care in Europe (ALSCarE).

Project Aim(s): The aim is to use epidemiologic and clinical datasets to track in detail the patient journey in ALS, and from this to provide a robust staging system, generate cost models and appropriate health economic metrics, and to inform the design of a user-friendly electronic care matrix for optimal ALS management that can be used by non-specialists, and that in turn can be modified for use in other neurodegenerative conditions.

Deciphering ALS Heterogeneity: A Precision Medicine Approach to Network-based Biomarker Development.

Project Aim(s):

(i) To continue to characterise the clinical subphenotypes of ALS and to further elucidate the observed clinical and genetic overlap between ALS and neuropsychiatric disorders by detailed study of endophenotypes in first and second degree relatives.

(ii) To identify heterogeneous disease subcohorts based on genomic signatures, including those that overlap between ALS and neuropsychiatric illness.

Defining and Addressing the Complex Needs of ALS Caregivers (ALSA-Cog).

Project Aim(s):

(i) Using existing data, to characterize the impact of ALS stage, cognitive and behavioural effects in ALS on caregiver burden, and to ascertain the unmet psychological and psychosocial needs of caregivers.

(ii) To provide new data focussing on subjective and objective aspects of caregiver burden that can inform psychologically tailored interventions that enable self-management of carer burden.

Project MinE.

Project Aim(s): To understand the genetic basis of ALS and to ultimately find a cure for this devastating, fatal neuromuscular disease, Project MinE aims to analyse the DNA of at least 15,000 ALS patients and 7,500 control subjects. The resulting 22,500 DNA profiles will be compared.